This page brought to you ad-free as a public service. Images have been censored at the request of our sponsors. You may view the full article on Wikipedia.

Paternal age effect

Information from Wikipedia, the free encyclopedia—a reliable source for your research. Click to cite:
Jump to: navigation, search

The paternal age effect (PAE) is the study of the statistical relationship between an advanced paternal age to sperm and semen abnormalities, fertility, pregnancy outcomes, birth outcome (such as birthweight), probability that the offspring will have a health-related condition, or risk of mortality, or social and other psychological outcomes. The paternal age effect is of two different types. One effect is directly related to advanced paternal age and autosomalmutations in the offspring. The other (PAE) is an indirect effect in relation to mutations on the X chromosome which are passed to daughters at risk for having sons with X-linked diseases.1 A 2009 review focusing on the effect to children said that the absolute risk for genetic anomalies in offspring is low, and concludes "There is no clear association between adverse health outcome and paternal age but longitudinal studies are needed."2

The genetic quality of sperm, as well as its volume and motility, all typically decrease with age,3 though telomere length of the sperm actually tends to increase, with possible positive consequences on offspring longevity.4 The population geneticist James F. Crow said that the fact that DNA in sperm degrades as men age and can then be passed along to children in permanently degraded and irreparable form, which they likely pass on as well, means that the "greatest mutational health hazard to the human genome is fertile older males". He described mutations that have a direct visible effect on the child's health and also mutations that can be latent or have minor visible effects on the child's health; many such mutations allow the child to reproduce, but cause more serious problems for grandchildren, greatgrandchildren and later generations.5

Because paternity did not become provable until 1970, and the cost of definitively establishing it only recently became low enough to do it on widespread basis, this has meant that only limited scientific research into paternal age effect problems of degraded DNA has been done. Harry Fisch, a physician who has done research in this area, says that research into paternal age effect degradation of DNA is "in its infancy".6

A 2014 study had experts suggesting that the debate based on mixed evidence whether a father’s age is linked to his child’s vulnerability to individual disorders like autism and schizophrenia had been settled.78 The result being that "Men have a biological clock of sorts because of random mutations in sperm over time". Dr. Patrick F. Sullivan, a professor of genetics at the University of North Carolina, who was not involved in the study said "This is the best paper I’ve seen on this topic, and it suggests several lines of inquiry into mental illness".

History

In 1912, Wilhelm Weinberg, a German physician, was the first person to hypothesize that non-inherited cases of achondroplasia could be more common in last-born children than in children born earlier to the same set of parents.9 Although Weinberg "made no distinction between paternal age, maternal age and birth order" in his hypothesis, by 1953 the term "paternal age effect" had occurred in the medical literature on achondroplasia.910:375

Scientific interest in paternal age effects increased in the late 20th and early 21st centuries because the average paternal age increased in countries such as the United Kingdom,11 Australia,12 and Germany,13 and because birth rates for fathers aged 30–54 years have risen between 1980 and 2006 in the United States.14 Possible reasons for the increases in average paternal age include increasing life expectancy and increasing rates of divorce and remarriage.13 Despite recent increases in average paternal age, however, the oldest father documented in the medical literature was born in 1840: George Isaac Hughes was 94 years old at the time of the birth of his son by his second wife, a 1935 article in the Journal of the American Medical Association stated that his fertility "has been definitely and affirmatively checked up medically," and he fathered a daughter in 1936 at age 96.13:3291516 In 2012, two 96-year-old men, Nanu Ram Jogi and Ramjit Raghav, both from India, claimed to have fathered children that year.,1718

Semen and sperm abnormalities

A 2001 review by Kidd et al. examined 1980-1999 scientific literature on variation in semen quality and fertility by male age.19 It concluded that older men had lower semen volume, lower sperm motility, and a decreased percent of normal sperm.19 The same researchers participated in a 2003 study that showed decreased semen volume and sperm motility with age.20 In addition, a study preformed in 1995 found a positive correlation between increasing male age and sperm aneuploidy, leading to a higher potential for genetic disorders.21

A study of semen samples from 66 men published in 2003 demonstrated a correlation of increasing age with more DNA damage, less apoptosis, and lower sperm motility.22 In 2006-2007 studies of sperm, age was again associated with DNA damage.2324

A study of semen samples from 100 men published in 2010 found low-level germline mosaicism in one third of infertile men, with increased incidence with advancing age.25

Fertility

A review of the literature by Kidd et al. (2001) determined that older men had decreased pregnancy rates, increased time to pregnancy, and increased subfecundity (i.e., infertility of a couple at a given point in time).19 In contrast, in 2001 a study detected "no association between male age and the fertilization rate of donated oocytes in vitro, pregnancy rates, or live birth rates";26 however, subsequent studies examining how well older men's sperm can fertilize donated eggs have been "contradictory."27 A 2002 study of 782 couples did find decreased fertility for older men; in specific, 35-39 year old women whose male partners were the same age had a probability of pregnancy under certain conditions of 0.29, but if the male partner was five years older the probability decreased to 0.18.28 A French study showed that male infertility shoots up after the age of 40.29 In a study of 1,024 couples undergoing ICSI, for couples in which the men are oligozoospermic, the chance of pregnancy decreased 5% for each year of paternal age, while no effect on age was seen in normozoospermic men.30

In a very recent retrospective cohort study of 10,965 Danish men, with both semen and parental data, the researchers found no convincing effect of either mother's or father's age on a man's semen quality. The study went on to conclude that as no trends were noted in the statistical data analysis, the few statistically significant results that did occur are likely attributable to chance. The researchers did, however state that a larger cohort may produce an identifiable trend. Furthermore, the cohort consisted of men who had been referred for infertility problems within their relationships, so do not represent the general population. Comparisons of semen quality across the cohort was, however, viewed by the researchers, as more significant than comparing to the general population.31

Adverse pregnancy outcomes and pre-eclampsia

Studies published between 2002 and 2008 have been consistent in associating advanced paternal age with miscarriage (spontaneous abortion),32333435 stillbirth,36 and fetal death (which includes both miscarriage and stillbirth).37 In addition, one 2002 study linked paternal age with pre-eclampsia, a complication of pregnancy that can be associated with adverse health outcomes for both the pregnant woman and the fetus.38

Adverse birth outcomes

A systematic review published in 2010 of 10 studies published in 1972-2008 concluded that the relationship of the risk of low birthweight in infants with paternal age is "saucer-shaped"; that is, the highest risks occur at low and at high paternal ages.39 Compared with a paternal age of 25–28 years as a reference group, the odds ratio for low birthweight was approximately 1.1 at a paternal age of 20 and approximately 1.2 at a paternal age of 50.39 There was no association of paternal age with preterm births or with small for gestational age births.39

In a 2008 retrospective cohort study of 2,614,966 births, a paternal age of 40 years or greater was not associated with neonatal death ("death of a live birth within 28 days") or post-neonatal death ("death of a live birth between 28–364 days of age") compared with a paternal age of 20–29 years.40 However, the risks of neonatal mortality and post-neonatal mortality were elevated for infants whose fathers were less than 20 years old.4041

Notable conditions and diseases

Evidence for a paternal age effect has been proposed for a number of conditions and diseases. In many of these, the statistical evidence of association is weak, and the association may be related by confounding factors, or behavioral differences.42 Conditions proposed to show correlation with paternal age include the following:2

Alzheimer's disease

Bertram and colleagues reviewed the 1982-1995 literature on paternal age and Alzheimer's disease, noting that five studies found a positive relationship, two found no relationship, and one found a negative relationship.43 Because some cases of Alzheimer's are related to genetics, the researchers performed a case-control study that examined 154 people: 52 had Alzheimer's with a low probability of having a major gene for Alzheimer's ("low MGAD"), 52 had Alzheimer's disease with a high probability of having a major gene for Alzheimer's disease ("high MGAD"), and 50 were age- and sex-matched controls.43 The mean age at onset in the two Alzheimer's groups was 66.6 years.43 The mean age of fathers of the "low MGAD" group was significantly higher than the mean age of fathers of people in the other two groups, which the researchers interpreted as evidence that increased paternal age is a risk factor for Alzheimer's not associated with a major gene.43 However, two studies published in 1997 and 2000 failed to find a relationship between paternal age and Alzheimer's.4445

Autism spectrum disorder

Most studies examining autism spectrum disorder (ASD) and advanced paternal age have demonstrated a statistically significant association between the two, but some have not.

  • A 2004 study from Australia compared 465 cases of ASD with 1,313 random population-based controls.46 The mean paternal age was significantly higher for cases than for controls (31.74 vs. 30.31 years); in a logistic regression, however, paternal age was not significant.46
  • A nested case-control study from Denmark by Larsson et al. published in 2005 involved 698 children with a diagnosis of autism and 17,450 controls.47 In an adjusted model including only perinatal factors, advanced paternal age was significantly associated with autism; however, in an adjusted model including perinatal factors, parental psychiatric history, and socioeconomic characteristics, advanced paternal age did not reach statistical significance.47
  • Another Danish study from 2005 followed 943,664 children less than 10 years old.48 Between 1994 and 2001, 818 of the children developed autism, and those whose fathers were 35 years or older had a risk of autism of 1.39 compared to those whose fathers were 25–29 years old.48
  • A matched, population-based case–control study from Denmark included 473 cases and 4,730 controls.49 In an unadjusted (crude) analysis published in 2006, the odds ratio for paternal age of >35 versus 25–29 years was statistically significant at 1.3, but an adjusted odds ratio of 1.2 did not reach statistical significance.49
  • Reichenberg et al. (2006) examined a cohort of 132,271 Israeli people, of whom 110 had been diagnosed with ASD.5051 They stated that people with fathers 30–39 years old were 1.62 times as likely, and people with fathers 40 years or older were 5.75 times as likely, to have ASD compared with people with fathers younger than 30 years old, controlling for year of birth, socioeconomic status, and maternal age.50
  • Comparing 593 children with ASD with 132,251 other births in the Kaiser Permanente health maintenance organization system in Northern California between 1995 and 1999, researchers found that paternal age was significantly and independently associated with risk for "autistic disorder... [and] Asperger disorder or pervasive developmental disorder not otherwise specified."52
  • Durkin et al. (2008) used a case-cohort study design with data from the Centers for Disease Control and Prevention; 253,347 children were in the cohort, of which 1,251 children with ASD were the cases.53 Paternal age of 40 years or greater was significantly and independently associated with risk of ASD, with an adjusted odds ratio of 1.4 versus a paternal age of 25–29 years.53
  • King et al. (2009) used California birth data from 1992 through 2000 and autism data to 2006.54 They determined that the risk of paternal age varied by birth cohort and was inflated if data are pooled across multiple birth cohorts.54
  • In a 2009 analysis of California birth data from 1989 through 2002 and autism data to 2006, an increase of 10 years in paternal age was associated with a 22% increase in risk for autism.55 The association between paternal age and autism was significant in most of the birth years studied (1989 and 1993–2002)55
  • A 2010 study of California birth data from 1996 to 2000 and autism data to 2006 examined geographic clusters of autism.56 Within the clusters, the researchers found a correlation between paternal age and autism, but the correlation was much weaker than that between parental education and autism.5657
  • A 2010 study of California birth data from 1990 to 1999 and autism data through 2006 revealed that "autism risk was associated with advancing paternal age primarily among mothers <30."5859
  • a 2013 study in Sweden linked autism to the grandfather's age 60

Bipolar disorder

Frans et al. (2008) considered 13,428 Swedish cases of bipolar disorder and 67,140 controls, and found an increased risk for bipolar disorder for people whose fathers were older than 24 years than those whose fathers were 20–24 years old at birth.6162 The risks increased with increasing age of the father, with even stronger associations when the analyses were limited to cases who developed bipolar disorder before the age of 20 years.61 A 2010 cohort study also using Swedish data was consistent with the findings of Frans et al..63

Cancers

In a systematic review and meta-analysis of 10 studies published between October 1, 1980 and June 21, 2007, researchers claimed that paternal age was associated with an increased risk of breast cancer, with an odds ratio of 1.12.64 The authors noted that adjustment or cross-stratification by maternal age may either reduce the association of paternal age and breast cancer, or cause the association to disappear entirely.64 A 1999 study from Sweden noted a risk ratio of 1.09 for each 10-year increment in paternal age for childhood brain cancer when adjusted for maternal age, but there was no association of paternal age with childhood leukemia.65 One 2002 study suggested that advanced paternal age is a risk factor for acute lymphoblastic leukemia.66 Analyses of cases of multiple endocrine neoplasia types 2A and 2B found that the mutations associated with the disease occur only on the paternally-derived chromosome, and that the mean paternal age of cases is higher than the mean paternal age of the population.6768

Reviewing the evidence linking paternal age to cancer, Tournaye concludes "again, associations are weak and data are prone to bias and confounding effects."2

Diabetes mellitus

Before 1998, four studies had been published concerning a possible association between diabetes mellitus type 1 and paternal age. Of these, Blom et al. (1989), Patterson et al. (1994), and Bock et al. (1994) were described as not finding an association, and Wadsworth et al. (1997) was described as finding a decreased risk with older paternal age.6970 The literature from 1998 onwards continues to show inconsistent results:

  • In a case-control study conducted in Taipei and published in 1998, a multiple logistic regression found an odds ratio of 0.33 for paternal ages 30–39 versus paternal ages under 30, while the risk for paternal ages 40 and above was not significantly different from the risk for paternal ages less than 30.71
  • In 1999, Rami et al. published the results of a population-based case-control study from Austria with 114 cases of type 1 diabetes and 495 matched controls.70 The mean paternal age of cases was 31.7 years, which was significantly higher than the mean paternal age of controls of 30.1 years.70
  • A 1999 Danish case-control study detected no association between paternal age and risk of type 1 diabetes.72
  • In a prospective study from the United Kingdom, Bingley et al. noted increasing relative risks for type 1 diabetes in childhood in each paternal age group 20 years and older versus paternal age less than 20; for example, in the multivariate analysis the relative risk for 40-45 year old fathers was 1.57.73
  • A Norwegian study of 2001 found no association with paternal age after adjustment for maternal age.74
  • In a 2005 study set in Northern Ireland, paternal age of 35 years or more was associated with a relative risk of 1.52 compared with a paternal age of less than 25 years.75

Down syndrome

In 1933, Lionel Penrose analyzed data for 727 children in 150 families and found no paternal age effect for the risk of Down syndrome after controlling for the maternal age effect.76 Largely based on a 2003 paper by Fisch et al. that found a paternal age effect only "in association with a maternal age of 35 years and older",7778 a 2009 review of the literature subsequent to Penrose's paper concludes that "a paternal-age effect exists, but is very small in comparison to maternal-age effect in Down syndrome prevalence".79

Intellectual disability and decreased intelligence

By 1998, "Intellectual disability or decreased learning capacity of unknown aetiology" was thought to be associated with increased paternal age.80 In 2005, Malaspina and colleagues detected an "inverted U-shaped relationship" between paternal age and intelligence quotients (IQs) in 44,175 people from Israel.81 There was a peak at paternal ages of 25-44; fathers younger than 25 and older than 44 tended to have children with lower IQs.81 Malaspina et al. also reviewed the literature and found that "at least a half dozen other studies ... have demonstrated significant associations between paternal age and human intelligence."81

A 2009 study by Saha et al. examined 33,437 children at 8 months, 4 years, and 7 years.8283 The researchers found that paternal age was associated with poorer scores in almost all neurocognitive tests used, but that maternal age was associated with better scores on the same tests.82 An editorial accompanying the paper by Saha et al. emphasized the importance of controlling for socioeconomic status in studies of paternal age and intelligence.84 A 2010 paper from Spain provided further evidence that average paternal age is elevated in cases of intellectual disability.85

Multiple sclerosis

A 2004 case-control study performed in Sweden involving 4,443 people with multiple sclerosis and 24,194 matched controls found a risk of 2.00 if the fathers were 51–55 years old versus 21–25 years old;86 however, two subsequent studies did not confirm the association.8788

Schizophrenia

Studies examining schizophrenia and paternal age include:

  • In a cohort of 87,907 people born in Jerusalem in 1964-1976 and followed through 1997, Malaspina et al. (2001) calculated relative risks for individuals' being diagnosed with schizophrenia given their fathers' ages at their births, controlling for maternal age and other factors.89 Compared with people whose fathers were younger than 25 years, the relative risk was 2.02 if a person's father was 45–49 years old and 2.96 if a person's father was 50 years or older.89 As noted in the newsmedia, the authors claimed that over 26% of the 658 schizophrenia cases could be attributed to paternal age.8990
  • A study published in 2004 by Sipos and colleagues found an association between paternal age and hospitalization for schizophrenia in persons with no family history of schizophrenia; the hazard ratio was 1.60 for each 10 year increase in paternal age.9192 The cohort included 712,014 Swedish people, of whom 639 (0.09%) had been admitted with a diagnosis of schizophrenia after follow-up for a mean of nine years.91
  • A 2009 meta-analysis was performed that included Malaspina et al.. (2001) and nine 1958-2008 studies with comparable available data.93 It concluded that paternal age was associated with schizophrenia "primarily among offspring of fathers ages 55 and over" and that "compared with other known risk factors for schizophrenia, advanced paternal age appears to be intermediate in magnitude."93
  • A 2010 case-control study from Spain using age as a continuous (not categorical) variable and using Bonferroni correction failed to find a higher paternal age in persons with diagnoses corresponding to ICD-10 codes for schizophrenia, schizotypal and delusional disorders.85

Other conditions

Other conditions and diseases which have been suggested as having a possible correlation with paternal age include: Achondroplasia8094 and chondrodystrophy,95 Acrodysostosis,8096 Aniridia,80 Apert syndrome,80949798 Basal cell nevus syndrome,8096 Cataracts,80 Cerebral palsy, athetoid/dystonic,80 CHARGE syndrome,999 Cleft palate,80100101 Cleidocranial dysostosis,8096 Costello syndrome,80 Craniosynostosis,102 Crouzon syndrome,809496 Diaphragmatic hernia,101 Duchenne muscular dystrophy,80 Exostoses, multiple,8096 congenital malformations in extremities,80103 Fibrodysplasia ossificans progressiva,8094 Heart defects,8095100 Hemangioma,100 Hemiplegia,80 Hemophilia A,80 Hydrocephalus,100 Klinefelter's syndrome,104 Lesch-Nyhan syndrome,80 Marfan syndrome,94 Nasal aplasia,80100 Neural tube defects,80 Oculodentodigital syndrome,8096 Osteogenesis imperfecta type IIA,80 Pfeiffer syndrome,8094 Polycystic kidney disease,80 Polyposis coli,80 Preauricular cyst,80100 Progeria,8096 Psychotic disorders,80105 von Recklinghausen neurofibromatosis,8094 Retinitis pigmentosa,80106 Retinoblastoma, bilateral,80 Situs inversus,95 Soto's basal cell nevus,8096 Thanatophoric dysplasia,80 Treacher-Collins Syndrome,8096 Tuberous sclerosis,80 Urethral stenosis,80100 Waardenburg syndrome,8096 and Wilms' tumor80

Mortality of offspring

As early as 1946, Pearl's analysis of human pedigree data led him to conclude that in order to be longevous, one should “pick long-lived parents."107 This would imply a positive effect of paternal age on lifespan, similar to the "Methuselah fly" effect seen in drosophila.108

A 2008 paper from Denmark found a U-shaped association between paternal age and the overall mortality rate in children (i.e., mortality rate up to age 18).109 Although the relative mortality rates were higher, the absolute numbers were low, because of the relatively low occurrence of genetic abnormality. The study has been criticized for not adjusting for maternal health, which could have a large effect on child mortality.110 Surprisingly, the researchers found a correlation between paternal age and offspring death by injury or poisoning, indicating the need to control for social and behavioral confounding factors.111

In 2012, Eisenberg et al. published a study which showed that greater age at paternity tends to increase telomere length in offspring for up to two generations. Since telomere length has effects on health and mortality, this may have effects on health and the "pace of senescence" in these offspring. The authors speculated that this effect may provide a mechanism by which populations have some plasticity in adapting longevity to different social and ecological contexts.4

Paternal mortality before adulthood of child

The risk of the father dying before the child becomes an adult increases by increased paternal age, such as can be demonstrated by the following data from France in 2007:112

Paternal age at childbirth 25 30 35 40 45
Risk of father not surviving until child's 18th birthday (in %)112 2.2 3.3 5.4 8.3 12.1

Social associations

Later age at parenthood is associated with a more stable family environment, higher socio-economic position, higher income and better living conditions, as well as better parenting practices,112 but it is more or less uncertain whether these entities are effects of advanced parental age, are contributors to advanced parental age, or common effects of a certain state such as personality type.

Pathophysiology

At least two hypothesized chains of causality exist whereby increased paternal age may lead to health effects:

  • Genetic mutations: In contrast to oogenesis, which involves 22 mitotic divisions before birth and 2 meiotic divisions after birth, spermatogenesis involves 30 mitotic divisions before puberty, and 4 mitotic and 2 meiotic divisions after puberty.9 Advanced paternal age may therefore lead to "copy error" in replication or the accumulation of mutagens, thereby leading to de novo mutations in sperm DNA.9 A study of 78 Icelandic families found that each additional year in the age of the father causes about two new mutations in the child.113
  • Epigenetic processes such as parental imprinting could explain the association between paternal age and schizophrenia.114

Clinical implications

The American College of Medical Genetics notes that there is no standard definition of "advanced paternal age."115 Although the College recommends obstetric ultrasonography at 18–20 weeks gestation in cases of advanced paternal age "to evaluate fetal growth and development," it notes that this procedure "is unlikely to detect many of the conditions of interest."115 Bray et al.. (2006) expressed an opinion that any adverse effects of advanced paternal age "should be weighed up against potential social advantages for children born to older fathers who are more likely to have progressed in their career and to have achieved financial security."11

See also

References

  1. ^ "Definition of Advanced paternal age". 
  2. ^ a b c H. Tournaye, "Male Reproductive Ageing," in Bewley, Ledger, and Nikolaou, eds., Reproductive Ageing, Cambridge University Press (2009), ISBN 9781906985134 (accessed 15 November 2013)
  3. ^ Gurevich, Rachel (06-10-2008). "Does Age Affect Male Fertility?". About.com:Fertility. About.com. Retrieved 14 February 2010. 
  4. ^ a b Eisenberg, Dan T.A.; Hayes, M. Geoffrey; Kuzawa, Christopher W. (June 11, 2012). "Delayed paternal age of reproduction in humans is associated with longer telomeres across two generations of descendants". Proc Natl Acad Sci U S A. 109 (26): 10251–10256. doi:10.1073/pnas.1202092109. Retrieved 28 June 2014. 
  5. ^ Crow, James F. (August 5, 1997). Proc Natl Acad Sci U S A. 94 (16). pp. 8380–8386. doi:10.1073/pnas.94.16.8380. PMC 33757. PMID 9237985. Retrieved 29 March 2013. 
  6. ^ Vanderbes, Jennifer (June 25, 2011). "What's That Ticking Sound? The Male Biological Clock". Wall Street Journal. Retrieved 3 December 2013. 
  7. ^ Benedict, Clary (February 26, 2014). "Mental Illness Risk Higher for Children of Older Fathers, Study Finds". New York Times. Retrieved 4 April 2014. 
  8. ^ Brian M. D’Onofrio, Martin E. Rickert, Emma Frans, Ralf Kuja-Halkola, Catarina Almqvist, Arvid Sjölander, Henrik Larsson, Paul Lichtenstein (2014). "Paternal Age at Childbearing and Offspring Psychiatric and Academic Morbidity". JAMA Psychiatry 71 (4): 432–438. doi:10.1001/jamapsychiatry.2013.4525. 
  9. ^ a b c d e Crow JF (2000). "The origins, patterns and implications of human spontaneous mutation". Nature Reviews Genetics 1 (1): 40–7. doi:10.1038/35049558. PMID 11262873. 
  10. ^ Krooth RS (1953). "Comments on the estimation of the mutation rate for achondroplasia". American Journal of Human Genetics 5 (4): 373–6. PMC 1716528. PMID 13104383. 
  11. ^ a b Bray I, Gunnell D, Smith GD (2006). "Advanced paternal age: How old is too old?". J Epidemiol Community Health 60 (10): 851–3. doi:10.1136/jech.2005.045179. PMC 2566050. PMID 16973530. 
  12. ^ Australian Bureau of Statistics (11 November 2009). "3301.0 - Births, Australia, 2008. Summary of findings. Births". Retrieved 25 February 2010. 
  13. ^ a b c Kühnert B, Nieschlag E (2004). "Reproductive functions of the ageing male". Hum Reprod Update 10 (4): 327–39. doi:10.1093/humupd/dmh030. PMID 15192059. 
  14. ^ Martin JA, Hamilton BE, Sutton PD, Ventura SJ, Menacker F, Kirmeyer S, Mathews TJ (2009). "Births: final data for 2006". National Vital Statistics Reports (Hyattsville, MD: National Center for Health Statistics) 57 (7): 1–104. Retrieved 25 February 2010. 
  15. ^ Seymour FI, Duffy C, Koerner A (1935). "A case of authenticated fertility in a man, aged 94". J Am Med Assoc 105 (18): 1423–4. doi:10.1001/jama.1935.92760440002009a. 
  16. ^ "A father again at 96; North Carolinan's baby a sister to boy born two years ago". New York Times. 4 June 1936. p. 10. 
  17. ^ Nanu Ram Jogi fathers another child aged 96, article in the Times of India, 16 October 2012
  18. ^ "World's oldest dad, 97, devastated after wife leaves him following disappearance of their son". The Daily Mail (London). 3 October 2013. 
  19. ^ a b c Kidd SA, Eskenazi B, Wyrobek AJ (2001). "Effects of male age on semen quality and fertility: a review of the literature". Fertil Steril 75 (2): 237–48. doi:10.1016/S0015-0282(00)01679-4. PMID 11172821. 
  20. ^ Eskenazi B, Wyrobek AJ, Sloter E, Kidd SA, Moore L, Young S, Moore D (2003). "The association of age and semen quality in healthy men". Hum Reprod 18 (2): 447–54. doi:10.1093/humrep/deg107. PMID 12571189. 
  21. ^ Robbins, WE; Baulch, JE; Moore, D. "Three-probe fluorescence in situ hybridization to assess chromosome X, Y, and 8 aneuploidy in sperm of 14 men from two healthy groups: evidence for a paternal age effect on sperm aneuploidy". Pub Med. MEDLINE. Retrieved 28 September 2014. 
  22. ^ Singh NP, Muller CH, Berger RE (2003). "Effects of age on DNA double-strand breaks and apoptosis in human sperm". Fertil Steril 80 (6): 1420–30. doi:10.1016/j.fertnstert.2003.04.002. PMID 14667878. 
  23. ^ Wyrobek AJ, Eskenazi B, Young S, Arnheim N, Tiemann-Boege I, Jabs EW, Glaser RL, Pearson FS, Evenson D (2006). "Advancing age has differential effects on DNA damage, chromatin integrity, gene mutations, and aneuploidies in sperm". Proc Natl Acad Sci U S A 103 (25): 9601–6. doi:10.1073/pnas.0506468103. PMC 1480453. PMID 16766665. 
  24. ^ Schmid TE, Eskenazi B, Baumgartner A, Marchetti F, Young S, Weldon R, Anderson D, Wyrobek AJ (2007). "The effects of male age on sperm DNA damage in healthy non-smokers". Hum Reprod 22 (1): 180–7. doi:10.1093/humrep/del338. PMID 17053003. 
  25. ^ Schiff JD, Luna M, Evans MI, Patel Z, Berry PK, Bar-Chama N (April 2010). "Sex chromosome micromosaicism in infertile men with normal karyotypes". Fertil. Steril. 93 (6): 1903–6. doi:10.1016/j.fertnstert.2007.11.094. PMID 20152966. 
  26. ^ Paulson RJ, Milligan RC, Sokol RZ (2001). "The lack of influence of age on male fertility". Am J Obstet Gynecol 184 (5): 818–22; discussion 822–4. doi:10.1067/mob.2001.113852. PMID 11303188. 
  27. ^ Luna M, Finkler E, Barritt J, Bar-Chama N, Sandler B, Copperman AB, Grunfeld L (2009). "Paternal age and assisted reproductive technology outcome in ovum recipients". Fertil Steril 92 (5): 1772–5. doi:10.1016/j.fertnstert.2009.05.036. PMID 19539905. 
  28. ^ Dunson DB, Colombo B, Baird DD (2002). "Changes with age in the level and duration of fertility in the menstrual cycle". Hum Reprod 17 (5): 1399–403. doi:10.1093/humrep/17.5.1399. PMID 11980771. 
  29. ^ Christian Nordqvist (2013). "Older Men's Sperm Raise Risk Of Genetic Problems In Offspring". Medical News Today. 
  30. ^ Ferreira RC, Braga DP, Bonetti TC, Pasqualotto FF, Iaconelli A, Borges E (April 2010). "Negative influence of paternal age on clinical intracytoplasmic sperm injection cycle outcomes in oligozoospermic patients". Fertil. Steril. 93 (6): 1870–4. doi:10.1016/j.fertnstert.2008.12.043. PMID 19409557. 
  31. ^ Lærke Priskorn, Tina K. Jensen, Rune Lindahl-Jacobsen, Niels E. Skakkebæk1, Erik Bostofte and Michael L. Eisenberg (2014). "Parental age at delivery and a man's semen quality". Hum Reprod 29 (5): 1097–1102. doi:10.1093/humrep/deu039. PMID 24578474. 
  32. ^ de la Rochebrochard E, Thonneau P (2002). "Paternal age and maternal age are risk factors for miscarriage; results of a multicentre European study". Hum Reprod 17 (6): 1649–56. doi:10.1093/humrep/17.6.1649. PMID 12042293. 
  33. ^ Slama R, Bouyer J, Windham G, Fenster L, Werwatz A, Swan SH (2005). "Influence of paternal age on the risk of spontaneous abortion". Am J Epidemiol 161 (9): 816–23. doi:10.1093/aje/kwi097. PMID 15840613. 
  34. ^ Kleinhaus K, Perrin M, Friedlander Y, Paltiel O, Malaspina D, Harlap S (2006). "Paternal age and spontaneous abortion". Obstet Gynecol 108 (2): 369–77. doi:10.1097/01.AOG.0000224606.26514.3a. PMID 16880308. 
  35. ^ Belloc S, Cohen-Bacrie P, Benkhalifa M, Cohen-Bacrie M, De Mouzon J, Hazout A, Ménézo Y (2008). "Effect of maternal and paternal age on pregnancy and miscarriage rates after intrauterine insemination". Reprod Biomed Online 17 (3): 392–7. doi:10.1016/S1472-6483(10)60223-4. PMID 18765010. dead link
  36. ^ Astolfi P, De Pasquale A, Zonta LA (2004). "Late paternity and stillbirth risk". Hum Reprod 19 (11): 2497–501. doi:10.1093/humrep/deh449. PMID 15319387. 
  37. ^ Nybo Andersen AM, Hansen KD, Andersen PK, Davey Smith G (2004). "Advanced paternal age and risk of fetal death: a cohort study". Am J Epidemiol 160 (12): 1214–22. doi:10.1093/aje/kwh332. PMID 15583374. 
  38. ^ Harlap S, Paltiel O, Deutsch L, Knaanie A, Masalha S, Tiram E, Caplan LS, Malaspina D, Friedlander Y (2002). "Paternal age and preeclampsia". Epidemiology 13 (6): 660–7. doi:10.1097/01.EDE.0000031708.99480.70. PMID 12410007. 
  39. ^ a b c Shah PS; Knowledge Synthesis Group on determinants of preterm/low birthweight births (2010). "Paternal factors and low birthweight, preterm, and small for gestational age births: a systematic review". Am J Obstet Gynecol 202 (2): 103–23. doi:10.1016/j.ajog.2009.08.026. PMID 20113689. 
  40. ^ a b Chen XK, Wen SW, Krewski D, Fleming N, Yang Q, Walker MC (2008). "Paternal age and adverse birth outcomes: teenager or 40+, who is at risk?". Hum Reprod 23 (6): 1290–6. doi:10.1093/humrep/dem403. PMID 18256111. 
  41. ^ Laurance J (7 February 2008). "Older fathers have healthier offspring". The Independent (London). Retrieved 25 February 2010. 
  42. ^ see Correlation does not imply causation
  43. ^ a b c d Bertram L, Busch R, Spiegl M, Lautenschlager NT, Müller U, Kurz A (1998). "Paternal age is a risk factor for Alzheimer disease in the absence of a major gene". Neurogenetics 1 (4): 277–80. doi:10.1007/s100480050041. PMID 10732803. 
  44. ^ Tsolaki M, Fountoulakis K, Chantzi E, Kazis A (1997). "Risk factors for clinically diagnosed Alzheimer's disease: a case-control study of a Greek population". Int Psychogeriatr 9 (3): 327–41. doi:10.1017/S104161029700447X. PMID 9513031. 
  45. ^ Ptok U, Papassotiropoulos A, Maier W, Heun R (2000). "Advanced parental age: a risk factor for Alzheimer's disease or depression in the elderly?". Int Psychogeriatr 12 (4): 445–51. doi:10.1017/S1041610200006566. PMID 11263711. 
  46. ^ a b Glasson EJ, Bower C, Petterson B, de Klerk N, Chaney G, Hallmayer JF (2004). "Perinatal factors and the development of autism: a population study". Arch Gen Psychiatry 61 (6): 618–27. doi:10.1001/archpsyc.61.6.618. PMID 15184241. 
  47. ^ a b Larsson HJ, Eaton WW, Madsen KM, Vestergaard M, Olesen AV, Agerbo E, Schendel D, Thorsen P, Mortensen PB (2005). "Risk factors for autism: perinatal factors, parental psychiatric history, and socioeconomic status". Am J Epidemiol 161 (10): 916–25; discussion 926–8. doi:10.1093/aje/kwi123. PMID 15870155. 
  48. ^ a b Lauritsen MB, Pedersen CB, Mortensen PB (2005). "Effects of familial risk factors and place of birth on the risk of autism: a nationwide register-based study". J Child Psychol Psychiatry 46 (9): 963–71. doi:10.1111/j.1469-7610.2004.00391.x. PMID 16108999. 
  49. ^ a b Maimburg RD, Vaeth M (2006). "Perinatal risk factors and infantile autism". Acta Psychiatr Scand 114 (4): 257–64. doi:10.1111/j.1600-0447.2006.00805.x. PMID 16968363. 
  50. ^ a b Reichenberg A, Gross R, Weiser M, Bresnahan M, Silverman J, Harlap S, Rabinowitz J, Shulman C, Malaspina D, Lubin G, Knobler HY, Davidson M, Susser E (2006). "Advancing paternal age and autism". Arch Gen Psychiatry 63 (9): 1026–32. doi:10.1001/archpsyc.63.9.1026. PMID 16953005. 
  51. ^ Vedantam S (5 September 2006). "Autism risk rises with age of father". Washington Post. Retrieved 25 February 2010. 
  52. ^ Croen LA, Najjar DV, Fireman B, Grether JK (2007). "Maternal and paternal age and risk of autism spectrum disorders". Arch Pediatr Adolesc Med 161 (4): 334–40. doi:10.1001/archpedi.161.4.334. PMID 17404129. 
  53. ^ a b Durkin MS, Maenner MJ, Newschaffer CJ, Lee LC, Cunniff CM, Daniels JL, Kirby RS, Leavitt L, Miller L, Zahorodny W, Schieve LA (2008). "Advanced Parental Age and the Risk of Autism Spectrum Disorder". Am J Epidemiol 168 (11): 1268–76. doi:10.1093/aje/kwn250. PMC 2638544. PMID 18945690. 
  54. ^ a b King MD, Fountain C, Dakhlallah D, Bearman PS (2009). "Estimated Autism Risk and Older Reproductive Age". Am J Public Health 99 (9): 1673–9. doi:10.2105/AJPH.2008.149021. PMC 2724463. PMID 19608957. 
  55. ^ a b Grether JK, Anderson MC, Croen LA, Smith D, Windham GC (2009). "Risk of autism and increasing maternal and paternal age in a large north American population". Am J Epidemiol 170 (9): 1118–26. doi:10.1093/aje/kwp247. PMID 19783586. 
  56. ^ a b Van Meter KC, Christiansen LE, Delwiche LD, Azari R, Carpenter TE, Hertz-Picciotto I (2010). "Geographic distribution of autism in California: A retrospective birth cohort analysis". Autism Res 3 (1): 19–29. doi:10.1002/aur.110. PMID 20049980. 
  57. ^ Thomas J (5 January 2010). "Autism may cluster among highly educated". BusinessWeek. Retrieved 25 February 2010. 
  58. ^ Shelton JF, Tancredi DJ, Hertz-Picciotto I (2010). "Independent and dependent contributions of advanced maternal and paternal ages to autism risk". Autism Res 3 (1): 30–39. doi:10.1002/aur.116. PMID 20143326. 
  59. ^ Rabin RC (8 February 2010). "Both parents’ ages linked to autism risk". New York Times. Retrieved 25 February 2010. 
  60. ^ Bakalar, Nicholas (29 March 2013). "Grandfathers' Age Linked to Autism". The New York Times. 
  61. ^ a b Frans EM, Sandin S, Reichenberg A, Lichtenstein P, Långström N, Hultman CM (2008). "Advancing paternal age and bipolar disorder". Arch Gen Psychiatry 65 (9): 1034–40. doi:10.1001/archpsyc.65.9.1034. PMID 18762589. 
  62. ^ Kahn M (2 September 2008). "Kids with older dads at higher bipolar risk: study". Reuters. Retrieved 25 February 2010. 
  63. ^ Menezes PR, Lewis G, Rasmussen F, Zammit S, Sipos A, Harrison GL, Tynelius P, Gunnell D (2010). "Paternal and maternal ages at conception and risk of bipolar affective disorder in their offspring". Psychol Med 40 (3): 477–85. doi:10.1017/S003329170999064X. PMID 19627644. 
  64. ^ a b Xue F, Michels KB (2007). "Intrauterine factors and risk of breast cancer: a systematic review and meta-analysis of current evidence". Lancet Oncol 8 (12): 1088–100. doi:10.1016/S1470-2045(07)70377-7. PMID 18054879. 
  65. ^ Hemminki K, Kyyrönen P, Vaittinen P (1999). "Parental age as a risk factor of childhood leukemia and brain cancer in offspring". Epidemiology 10 (3): 271–5. doi:10.1097/00001648-199905000-00014. PMID 10230837. 
  66. ^ Murray L, McCarron P, Bailie K, Middleton R, Davey Smith G, Dempsey S, McCarthy A, Gavin A (2002). "Association of early life factors and acute lymphoblastic leukaemia in childhood: historical cohort study". Br J Cancer 86 (3): 356–61. doi:10.1038/sj.bjc.6600012. PMC 2375228. PMID 11875699. 
  67. ^ Carlson KM, Bracamontes J, Jackson CE, Clark R, Lacroix A, Wells SA Jr, Goodfellow PJ (1994). "Parent-of-origin effects in multiple endocrine neoplasia type 2B". American Journal of Human Genetics 55 (6): 1076–82. PMC 1918453. PMID 7977365. 
  68. ^ Schuffenecker I, Ginet N, Goldgar D, Eng C, Chambe B, Boneu A, Houdent C, Pallo D, Schlumberger M, Thivolet C, Lenoir GM; Le Groupe d'Etude des Tumeurs a Calcitonine (1997). "Prevalence and parental origin of de novo RET mutations in multiple endocrine neoplasia type 2A and familial medullary thyroid carcinoma. Le Groupe d'Etude des Tumeurs a Calcitonine". American Journal of Human Genetics 60 (1): 233–7. PMC 1712555. PMID 8981969. 
  69. ^ Patterson CC, Carson DJ, Hadden DR, Waugh NR, Cole SK (1994). "A case-control investigation of perinatal risk factors for childhood IDDM in Northern Ireland and Scotland". Diabetes Care 17 (5): 376–81. doi:10.2337/diacare.17.5.376. PMID 8062603. 
  70. ^ a b c Rami B, Schneider U, Imhof A, Waldhör T, Schober E (1999). "Risk factors for type I diabetes mellitus in children in Austria". Eur J Pediatr 158 (5): 362–6. doi:10.1007/s004310051092. PMID 10333115. 
  71. ^ Tai TY, Wang CY, Lin LL, Lee LT, Tsai ST, Chen CJ (1998). "A case-control study on risk factors for Type 1 diabetes in Taipei City". Diabetes Res Clin Pract 42 (3): 197–203. doi:10.1016/S0168-8227(98)00105-3. PMID 9925351. 
  72. ^ Bache I, Bock T, Vølund A, Buschard K (1999). "Previous maternal abortion, longer gestation, and younger maternal age decrease the risk of type 1 diabetes among male offspring". Diabetes Care 22 (7): 1063–5. doi:10.2337/diacare.22.7.1063. PMID 10388968. 
  73. ^ Bingley PJ, Douek IF, Rogers CA, Gale EA (2000). "Influence of maternal age at delivery and birth order on risk of type 1 diabetes in childhood: prospective population based family study". BMJ 321 (7258): 420–4. doi:10.1136/bmj.321.7258.420. PMC 27456. PMID 10938050. 
  74. ^ Stene LC, Magnus P, Lie RT, Søvik O, Joner G (2001). "Maternal and paternal age at delivery, birth order, and risk of childhood onset type 1 diabetes: population based cohort study". BMJ 323 (7309): 369. doi:10.1136/bmj.323.7309.369. PMC 37395. PMID 11509426. 
  75. ^ Cardwell CR, Carson DJ, Patterson CC (2005). "Parental age at delivery, birth order, birth weight and gestational age are associated with the risk of childhood Type 1 diabetes: a UK regional retrospective cohort study". Diabet Med 22 (2): 200–6. doi:10.1111/j.1464-5491.2005.01369.x. PMID 15660739. 
  76. ^ Penrose LS (1933). "The relative effects of paternal and maternal age in mongolism". J Genet 27 (2): 219–224. doi:10.1007/BF02984413. 
  77. ^ Fisch H, Hyun G, Golden R, Hensle TW, Olsson CA, Liberson GL (2003). "The influence of paternal age on down syndrome". J Urol 169 (6): 2275–8. doi:10.1097/01.ju.0000067958.36077.d8. PMID 12771769. 
  78. ^ Warner J (1 July 2003). "Dad's age raises down syndrome risk, too". WebMD Health News. Retrieved 25 February 2010. 
  79. ^ Girirajan S (2009). "Parental-age effects in Down syndrome". J Genet 88 (1): 1–7. doi:10.1007/s12041-009-0001-6. PMID 19417538. 
  80. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak al am an Tarín JJ, Brines J, Cano A (1998). "Long-term effects of delayed parenthood". Hum Reprod 13 (9): 2371–6. doi:10.1093/humrep/13.9.2371. PMID 9806250. 
  81. ^ a b c Malaspina D, Reichenberg A, Weiser M, Fennig S, Davidson M, Harlap S, Wolitzky R, Rabinowitz J, Susser E, Knobler HY (2005). "Paternal age and intelligence: implications for age-related genomic changes in male germ cells". Psychiatr Genet 15 (2): 117–25. doi:10.1097/00041444-200506000-00008. PMID 15900226. 
  82. ^ a b Saha S, Barnett AG, Foldi C, Burne TH, Eyles DW, Buka SL, McGrath JJ (2009). "Advanced Paternal Age Is Associated with Impaired Neurocognitive Outcomes during Infancy and Childhood". In Brayne, Carol. PLoS Med 6 (3): e40. doi:10.1371/journal.pmed.1000040. PMC 2653549. PMID 19278291. 
  83. ^ Dayton L (10 March 2009). "Not the sharpest? Blame old dad". The Australian. Retrieved 25 February 2010. 
  84. ^ Cannon M (2009). "Contrasting Effects of Maternal and Paternal Age on Offspring Intelligence: The clock ticks for men too". PLoS Med 6 (3): e42. doi:10.1371/journal.pmed.1000042. PMC 2653550. PMID 19278293. 
  85. ^ a b Lopez-Castroman J, Gómez DD, Belloso JJ, Fernandez-Navarro P, Perez-Rodriguez MM, Villamor IB, Navarrete FF, Ginestar CM, Currier D, Torres MR, Navio-Acosta M, Saiz-Ruiz J, Jimenez-Arriero MA, Baca-Garcia E (2010). "Differences in maternal and paternal age between schizophrenia and other psychiatric disorders". Schizophr Res 116 (2–3): 184–90. doi:10.1016/j.schres.2009.11.006. PMID 19945257. 
  86. ^ Montgomery SM, Lambe M, Tomas O, Ekbom A (2004). "Paternal age, family size, and risk of multiple sclerosis". Epidemiology 15 (6): 717–23. doi:10.1097/01.ede.0000142138.46167.69. PMID 15475721. 
  87. ^ Bager P, Nielsen NM, Bihrmann K, Frisch M, Wohlfart J, Koch-Henriksen N, Melbye M, Westergaard T (2006). "Sibship characteristics and risk of multiple sclerosis: a nationwide cohort study in Denmark". Am J Epidemiol 163 (12): 1112–7. doi:10.1093/aje/kwj148. PMID 16675539. 
  88. ^ Ramagopalan SV, Dyment DA, Guimond C, Yee IM, Ebers GC, Sadovnick AD (2010). "No effect of parental age on risk of multiple sclerosis: a population-based study". Neuroepidemiology 34 (2): 106–109. doi:10.1159/000268822. PMID 20051693. 
  89. ^ a b c Malaspina D, Harlap S, Fennig S, Heiman D, Nahon D, Feldman D, Susser ES (2001). "Advancing paternal age and the risk of schizophrenia". Arch Gen Psychiatry 58 (4): 361–7. doi:10.1001/archpsyc.58.4.361. PMID 11296097. 
  90. ^ Radford T (13 April 2001). "Schizophrenia linked to father's age". The Guardian (London). Retrieved 25 February 2010. 
  91. ^ a b Sipos A, Rasmussen F, Harrison G, Tynelius P, Lewis G, Leon DA, Gunnell D (2004). "Paternal age and schizophrenia: a population based cohort study". BMJ 329 (7474): 1070. doi:10.1136/bmj.38243.672396.55. PMC 526116. PMID 15501901. 
  92. ^ Bhattacharya S (22 October 2004). "Father's age linked to schizophrenia risk". New Scientist. Retrieved 25 February 2010. 
  93. ^ a b Torrey EF, Buka S, Cannon TD, Goldstein JM, Seidman LJ, Liu T, Hadley T, Rosso IM, Bearden C, Yolken RH (2009). "Paternal age as a risk factor for schizophrenia: how important is it?". Schizophr Res 114 (1–3): 1–5. doi:10.1016/j.schres.2009.06.017. PMID 19683417. 
  94. ^ a b c d e f g Risch N, Reich EW, Wishnick MM, McCarthy JG (1987). "Spontaneous mutation and parental age in humans". American Journal of Human Genetics 41 (2): 218–48. PMC 1684215. PMID 3618593. 
  95. ^ a b c Lian ZH, Zack MM, Erickson JD (1986). "Paternal age and the occurrence of birth defects". American Journal of Human Genetics 39 (5): 648–60. PMC 1684057. PMID 3788977. 
  96. ^ a b c d e f g h i j Jones KL, Smith DW, Harvey MA, Hall BD, Quan L (1975). "Older paternal age and fresh gene mutation: data on additional disorders". J Pediatr 86 (1): 84–8. doi:10.1016/S0022-3476(75)80709-8. PMID 1110452. 
  97. ^ Tolarova MM, Harris JA, Ordway DE, Vargervik K (1997). "Birth prevalence, mutation rate, sex ratio, parents' age, and ethnicity in Apert syndrome". American Journal of Medical Genetics 72 (4): 394–8. doi:10.1002/(SICI)1096-8628(19971112)72:4<394::AID-AJMG4>3.0.CO;2-R. PMID 9375719. 
  98. ^ Yoon SR, Qin J, Glaser RL, Jabs EW, Wexler NS, Sokol R, Arnheim N, Calabrese P (2009). "The Ups and Downs of Mutation Frequencies during Aging Can Account for the Apert Syndrome Paternal Age Effect". In Walsh, Bruce. PLoS Genet 5 (7): e1000558. doi:10.1371/journal.pgen.1000558. PMC 2700275. PMID 19593369. 
  99. ^ Blake KD, Prasad C (2006). "CHARGE syndrome". Orphanet J Rare Dis 1: 34. doi:10.1186/1750-1172-1-34. PMC 1586184. PMID 16959034. 
  100. ^ a b c d e f g Savitz DA, Schwingl PJ, Keels MA (1991). "Influence of paternal age, smoking, and alcohol consumption on congenital anomalies". Teratology 44 (4): 429–40. doi:10.1002/tera.1420440409. PMID 1962288. 
  101. ^ a b Green RF, Devine O, Crider KS, Olney RS, Archer N, Olshan AF, Shapira SK (2010). "Association of Paternal Age and Risk for Major Congenital Anomalies from the National Birth Defects Prevention Study, 1997–2004". Annals of Epidemiology 20 (3): 241–9. doi:10.1016/j.annepidem.2009.10.009. PMC 2824069. PMID 20056435. 
  102. ^ Rasmussen SA, Yazdy MM, Frías JL, Honein MA (2008). "Priorities for public health research on craniosynostosis: summary and recommendations from a Centers for Disease Control and Prevention-sponsored meeting". American Journal of Medical Genetics 146A (2): 149–58. doi:10.1002/ajmg.a.32106. PMID 18080327. 
  103. ^ Zhu JL, Madsen KM, Vestergaard M, Olesen AV, Basso O, Olsen J (2005). "Paternal age and congenital malformations". Hum Reprod 20 (11): 3173–7. doi:10.1093/humrep/dei186. PMID 16006461. 
  104. ^ BRS Genetics - Dudek 2009
  105. ^ Miller B, Pihlajamaa J, Haukka J, Cannon M, Henriksson M, Heilä H, Huttunen M, Tanskanen A, Lönnqvist J, Suvisaari J, Kirkpatrick B (16 Feb 2010). "Paternal age and mortality in nonaffective psychosis". Schizophr Res 121 (1–3): 218–26. doi:10.1016/j.schres.2010.01.020. PMID 20163936. 
  106. ^ Kaplan J, Bonneau D, Frézal J, Munnich A, Dufier JL (1990). "Clinical and genetic heterogeneity in retinitis pigmentosa". Hum Genet 85 (6): 635–42. doi:10.1007/BF00193589. PMID 2227956. 
  107. ^ Pearl, Raymond, Man the Animal, Principia Press, Bloomington, IN (1946). (Lectures originally delivered at Indiana University in October, 1938, as the Patten Foundation lectures) archive
  108. ^ Claudia Dreifus, Live Longer With Evolution? Evidence May Lie in Fruit FliesThe New York Times, December 6, 2005. (accessed Nov. 15 2013)
  109. ^ Zhu JL, Vestergaard M, Madsen KM, Olsen J (2008). "Paternal age and mortality in children". Eur J Epidemiol 23 (7): 443–7. doi:10.1007/s10654-008-9253-3. PMID 18437509. 
  110. ^ "In this particular study, no adjustment was made for the health of the mother, and this could have had a large effect on child mortality." National Health Service (UK), "Older Dads and the Death of Children," (accessed 15 November 2013)
  111. ^ Tournaye 2009, p. 102
  112. ^ a b c Schmidt, L.; Sobotka, T.; Bentzen, J. G.; Nyboe Andersen, A.; on behalf of the ESHRE Reproduction Society Task Force (2011). "Demographic and medical consequences of the postponement of parenthood". Human Reproduction Update 18 (1): 29–43. doi:10.1093/humupd/dmr040. PMID 21989171. 
  113. ^ Kong A, Frigge ML, Masson G, Besenbacher S, Sulem P, Magnusson G, Gudjonsson SA, Sigurdsson A, Jonasdottir A, Jonasdottir A, Wong WS, Sigurdsson G, Walters GB, Steinberg S, Helgason H, Thorleifsson G, Gudbjartsson DF, Helgason A, Magnusson OT, Thorsteinsdottir U, Stefansson K (2012). "Rate of de novo mutations and the importance of father's age to disease risk". Nature 488 (7412): 471–5. doi:10.1038/nature11396. PMC 3548427. PMID 22914163. 
  114. ^ Perrin MC, Brown AS, Malaspina D (2007). "Aberrant Epigenetic Regulation Could Explain the Relationship of Paternal Age to Schizophrenia". Schizophr Bull 33 (6): 1270–3. doi:10.1093/schbul/sbm093. PMC 2779878. PMID 17712030. 
  115. ^ a b Toriello HV, Meck JM; Professional Practice and Guidelines Committee, American College of Medical Genetics (2008). "Statement on guidance for genetic counseling in advanced paternal age". Genet Med 10 (6): 457–60. doi:10.1097/GIM.0b013e318176fabb. PMC 3111019. PMID 18496227. 

Further reading

  • Fisch H, Braun S (2005). The male biological clock: the startling news about aging, sexuality, and fertility in men. New York: Free Press. ISBN 0-7432-5991-2. 
  • Gavrilov, L.A., Gavrilova, N.S. Human longevity and parental age at conception. In: J.-M.Robine, T.B.L. Kirkwood, M. Allard (eds.) Sex and Longevity: Sexuality, Gender, Reproduction, Parenthood, Berlin, Heidelberg: Springer-Verlag, 2000, 7-31.
  • Gavrilov, L.A., Gavrilova, N.S. Parental age at conception and offspring longevity. Reviews in Clinical Gerontology, 1997, 7: 5-12.
  • Gavrilov, L.A., Gavrilova, N.S. When Fatherhood Should Stop? Letter. Science, 1997, 277(5322): 17-18.

External links


Content from Wikipedia, the Free Encyclopedia

What Is This Site? The Ultimate Study Guide is a mirror of English Wikipedia. It exists in order to provide Wikipedia content to those who are unable to access the main Wikipedia site due to draconian government, employer, or school restrictions. The site displays all the text content from Wikipedia. Our sponsors generously cover part of the cost of hosting this site, and their ads are shown as part of this agreement. We regret that we are unable to display certain controversial images on some pages the site at the request of the sponsors. If you need to see images which we are unable to show, we encourage you to view Wikipedia directly if possible, and apologize for this inconvenience.

A product of XPR Content Systems. 47 Union St #9K, Grand Falls-Windsor NL A2A 2C9 CANADA