Skip to main content Accessibility help
  • Get access
    Check if you have access via personal or institutional login
  • Cited by 1
  • Print publication year: 2013
  • Online publication date: April 2013

Chapter 10 - Paternal aging and increased risk of congenital disease, psychiatric disorders, and cancer


1. KiddSA, EskenaziB, WyrobekAJ. Effects of male age on semen quality and fertility: a review of the literature. Fertil Steril. 2001;75(2):237–48.
2. ZhuJL, VestergaardM, MadsenKMet al. Paternal age and mortality in children. Eur J Epidemiol. 2008;23(7):443–7.
3. WeinbergW. Zur vererbung des zwergwuches. Arch Rassen-u, Gesel Biology. 1912;9:710–18.
4. PenroseLS. Parental age and mutation. Lancet. 1955;269(6885):312–13.
5. VogelF, MotulskyAG. Human Genetics. Berlin: Springer; 1977.
6. YoonPW, FreemanSB, ShermanSLet al. Advanced maternal age and the risk of Down syndrome characterized by the meiotic stage of chromosomal error: a population-based study. Am J Hum Genet. 1996;58(3):628–33.
7. KurahashiH, TsutsumiM, NishiyamaSet al. Molecular basis of maternal age-related increase in oocyte aneuploidy. Congenit Anom (Kyoto). 2012;52(1):8–15.
8. JonesKT, LaneSI. Chromosomal, metabolic, environmental, and hormonal origins of aneuploidy in mammalian oocytes. Exp Cell Res. 2012;318(12):1394–9.
9. KhodjakovA, PinesJ. Centromere tension: a divisive issue. Nat Cell Biol. 2010;12(10):919–23.
10. SartorelliEM, MazzucattoLF, de Pina-NetoJM. Effect of paternal age on human sperm chromosomes. Fertil Steril. 2001;76(6):1119–23.
11. ZhuJL, MadsenKM, VestergaardMet al. Paternal age and congenital malformations. Hum Reprod. 2005;20(11):3173–7.
12. WyrobekAJ, EskenaziB, YoungSet al. Advancing age has differential effects on DNA damage, chromatin integrity, gene mutations, and aneuploidies in sperm. Proc Natl Acad Sci USA. 2006;103(25):9601–6.
13. HassoldT, AbruzzoM, AdkinsKet al. Human aneuploidy: incidence, origin, and etiology. Environ Mol Mutagen. 1996;28(3):167–75.
14. TarinJJ, BrinesJ, CanoA. Long-term effects of delayed parenthood. Hum Reprod. 1998;13(9):2371–6.
15. WilkinDJ, SzaboJK, CameronRet al. Mutations in fibroblast growth-factor receptor 3 in sporadic cases of achondroplasia occur exclusively on the paternally derived chromosome. Am J Hum Genet. 1998;63(3):711–16.
16. Tiemann-BoegeI, NavidiW, GrewalRet al. The observed human sperm mutation frequency cannot explain the achondroplasia paternal age effect. Proc Natl Acad Sci USA. 2002;99(23):14,952–7.
17. RischN, ReichEW, WishnickMMet al. Spontaneous mutation and parental age in humans. Am J Hum Genet. 1987;41(2):218–48.
18. GlaserRL, BromanKW, SchulmanRLet al. The paternal-age effect in Apert syndrome is due, in part, to the increased frequency of mutations in sperm. Am J Hum Genet. 2003;73(4):939–47.
19. GorielyA, McVeanGA, RojmyrMet al. Evidence for selective advantage of pathogenic FGFR2 mutations in the male germ line. Science. 2003;301(5633):643–6.
20. MoloneyDM, SlaneySF, OldridgeMet al. Exclusive paternal origin of new mutations in Apert syndrome. Nat Genet. 1996;13(1):48–53.
21. GlaserRL, JiangW, BoyadjievSAet al. Paternal origin of FGFR2 mutations in sporadic cases of Crouzon syndrome and Pfeiffer syndrome. Am J Hum Genet. 2000;66(3):768–77.
22. SchuffeneckerI, GinetN, GoldgarDet al. 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. Am J Hum Genet. 1997;60(1):233–7.
23. CrowJF. The origins, patterns and implications of human spontaneous mutation. Nat Rev Genet. 2000;1(1):40–7.
24. SnajderovaM, RiccardiVM, PetrakBet al. The importance of advanced parental age in the origin of neurofibromatosis type 1. Am J Med Genet A. 2012;158A(3):519–23.
25. LoweX, EskenaziB, NelsonDOet al. Frequency of XY sperm increases with age in fathers of boys with Klinefelter syndrome. Am J Hum Genet. 2001;69(5):1046–54.
26. GoldbergYP, KremerB, AndrewSEet al. Molecular analysis of new mutations for Huntington’s disease: intermediate alleles and sex of origin effects. Nat Genet. 1993;5(2):174–9.
27. FarrerLA, CupplesLA, KielyDKet al. Inverse relationship between age at onset of Huntington disease and paternal age suggests involvement of genetic imprinting. Am J Hum Genet. 1992;50(3):528–35.
28. SinghNP, MullerCH, BergerRE. Effects of age on DNA double-strand breaks and apoptosis in human sperm. Fertil Steril. 2003;80(6):1420–30.
29. CrowJF. Development. There’s something curious about paternal-age effects. Science. 2003;301(5633):606–7.
30. Bennett-BakerPE, WilkowskiJ, BurkeDT. Age-associated activation of epigenetically repressed genes in the mouse. Genetics. 2003;165(4):2055–62.
31. AdkinsRM, ThomasF, TylavskyFAet al. Parental ages and levels of DNA methylation in the newborn are correlated. BMC Med Genet. 2011;12:47.
32. HemminkiK, KyyronenP, VaittinenP. Parental age as a risk factor of childhood leukemia and brain cancer in offspring. Epidemiology. 1999;10(3):271–5.
33. MurrayL, McCarronP, BailieKet al. Association of early life factors and acute lymphoblastic leukaemia in childhood: historical cohort study. Br J Cancer. 2002;86(3):356–61.
34. LuY, MaH, Sullivan-HalleyJet al. Parents’ ages at birth and risk of adult-onset hematologic malignancies among female teachers in California. Am J Epidemiol. 2010;171(12):1262–9.
35. YipBH, PawitanY, CzeneK. Parental age and risk of childhood cancers: a population-based cohort study from Sweden. Int J Epidemiol. 2006;35(6):1495–503.
36. ZhangY, KregerBE, DorganJFet al. Parental age at child’s birth and son’s risk of prostate cancer. The Framingham study. Am J Epidemiol. 1999;150(11):1208–12.
37. ChoiJY, LeeKM, ParkSKet al. Association of paternal age at birth and the risk of breast cancer in offspring: a case control study. BMC Cancer. 2005;5:143.
38. MillsMB, HudginsL, BaliseRRet al. Mutation risk associated with paternal and maternal age in a cohort of retinoblastoma survivors. Hum Genet. 2012;131(7):1115–22.
39. PuleoCM, ReichenbergA, SmithCJet al. Do autism-related personality traits explain higher paternal age in autism?Mol Psychiatry. 2008;13(3):243–4.
40. FombonneE. The prevalence of autism. J Am Med Assoc 2003;289(1):87–9.
41. FombonneE. The epidemiology of autism: a review. Psychol Med. 1999;29(4):769–86.
42. ReichenbergA, GrossR, WeiserMet al. Advancing paternal age and autism. Arch Gen Psychiatry. 2006;63(9):1026–32.
43. PuleoCM, SchmeidlerJ, ReichenbergAet al. Advancing paternal age and simplex autism. Autism. 2012;16(4):367–80.
44. SebatJ, LakshmiB, MalhotraDet al. Strong association of de novo copy number mutations with autism. Science. 2007;316(5823):445–9.
45. GeschwindDH. Advances in autism. Annu Rev Med. 2009;60:367–80.
46. BrownAS, SchaeferCA, WyattRJet al. Paternal age and risk of schizophrenia in adult offspring. Am J Psychiatry. 2002;159(9):1528–33.
47. MalaspinaD, HarlapS, FennigSet al. Advancing paternal age and the risk of schizophrenia. Arch Gen Psychiatry. 2001;58(4):361–7.
48. SiposA, RasmussenF, HarrisonGet al. Paternal age and schizophrenia: a population based cohort study. Br Med J. 2004;329(7474):1070.
49. FransEM, SandinS, ReichenbergAet al. Advancing paternal age and bipolar disorder. Arch Gen Psychiatry. 2008;65(9):1034–40.
50. SahaS, BarnettAG, FoldiCet al. Advanced paternal age is associated with impaired neurocognitive outcomes during infancy and childhood. PLoS Med. 2009;6(3):e40.
51. SahaS, BarnettAG, BukaSLet al. Maternal age and paternal age are associated with distinct childhood behavioural outcomes in a general population birth cohort. Schizophr Res. 2009;115(2–3):130–5.
52. AurouxM. Decrease of learning capacity in offspring with increasing paternal age in the rat. Teratology. 1983;27(2):141–8.
53. FransEM, McGrathJJ, SandinSet al. Advanced paternal and grandpaternal age and schizophrenia: a three-generation perspective. Schizophr Res. 2011;133(1–3):120–4.
54. TolarovaMM, HarrisJA, OrdwayDEet al. Birth prevalence, mutation rate, sex ratio, parents’ age, and ethnicity in Apert syndrome. Am J Med Genet. 1997;72(4):394–8.
55. JonesKL, SmithDW, HarveyMAet al. Older paternal age and fresh gene mutation: data on additional disorders. J Pediatr. 1975;86(1):84–8.
56. OlshanAF, SchnitzerPG, BairdPA. Paternal age and the risk of congenital heart defects. Teratology. 1994;50(1):80–4.
57. HarvilleEW, WilcoxAJ, LieRTet al. Epidemiology of cleft palate alone and cleft palate with accompanying defects. Eur J Epidemiol. 2007;22(6):389–95.
58. OverhauserJ, McMahonJ, OberlenderSet al. Parental origin of chromosome 5 deletions in the Cri-du-chat syndrome. Am J Med Genet. 1990;37(1):83–6.
59. BucherK, IonasescuV, HansonJ. Frequency of new mutants among boys with Duchenne muscular dystrophy. Am J Med Genet. 1980;7(1):27–34.
60. MurdochJL, WalkerBA, McKusickVA. Parental age effects on the occurrence of new mutations for the Marfan syndrome. Ann Hum Genet. 1972;35(3):331–6.
61. MulliganLM, EngC, HealeyCSet al. A de novo mutation of the RET proto-oncogene in a patient with men 2a. Hum Mol Genet. 1994;3(6):1007–8.
62. CarlsonKM, BracamontesJ, JacksonCEet al. Parent-of-origin effects in multiple endocrine neoplasia type 2b. Am J Hum Genet. 1994;55(6):1076–82.
63. KluweL, MautnerV, ParryDMet al. The parental origin of new mutations in neurofibromatosis 2. Neurogenetics. 2000;3(1):17–24.
64. YoungID, ThompsonEM, HallCMet al. Osteogenesis imperfecta type IIA: evidence for dominant inheritance. J Med Genet. 1987;24(7):386–9.
65. ErikssonM, BrownWT, GordonLBet al. Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature. 2003;423(6937):293–8.
66. KaplanJ, BonneauD, FrezalJet al. Clinical and genetic heterogeneity in retinitis pigmentosa. Hum Genet. 1990;85(6):635–42.
67. WirthB, SchmidtT, HahnenEet al. De novo rearrangements found in 2% of index patients with spinal muscular atrophy: mutational mechanisms, parental origin, mutation rate, and implications for genetic counseling. Am J Hum Genet. 1997;61(5):1102–11.
68. LianZH, ZackMM, EricksonJD. Paternal age and the occurrence of birth defects. Am J Hum Genet. 1986;39(5):648–60.
69. Martinez-FriasML, Ramos-ArroyoMA, SalvadorJ. Thanatophoric dysplasia: an autosomal dominant condition?Am J Med Genet. 1988;31(4):815–20.
70. SplendoreA, JabsEW, FelixTMet al. Parental origin of mutations in sporadic cases of Treacher Collins syndrome. Eur J Hum Genet. 2003;11(9):718–22.
71. LuJH, ChungMY, HwangBet al. Prevalence and parental origin in tetralogy of Fallot associated with chromosome 22q11 microdeletion. Pediatrics. 1999;104(1 Pt 1):87–90.
72. OlsonJM, BreslowNE, BeckwithJB. Wilms’ tumour and parental age: a report from the National Wilms’ Tumour Study. Br J Cancer. 1993;67(4):813–18.
73. BertramL, BuschR, SpieglMet al. Paternal age is a risk factor for Alzheimer disease in the absence of a major gene. Neurogenetics. 1998;1(4):277–80.
74. JayasekaraR, StreetJ. Parental age and parity in dyslexic boys. J Biosoc Sci. 1978;10(3):255–61.
75. AmirRE, ZoghbiHY. Rett syndrome: methyl-CpG-binding protein 2 mutations and phenotype-genotype correlations. Am J Med Genet. 2000;97(2):147–52.