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Age at fatherhood: heritability and associations with psychiatric disorders

Published online by Cambridge University Press:  12 August 2016

E. M. Frans ,
P. Lichtenstein ,
C. M. Hultman  and
R. Kuja-Halkola
E. M. Frans*
Affiliation:
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Sweden Department of Psychiatry, University of Oxford, Oxford, UK
P. Lichtenstein
Affiliation:
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Sweden
C. M. Hultman
Affiliation:
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Sweden
R. Kuja-Halkola
Affiliation:
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Sweden
*
*Address for correspondence: Dr E. Frans, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, SE-171 77 Stockholm, Sweden. (Email: [email protected])
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Abstract

Background

Advancing paternal age has been linked to psychiatric disorders. These associations might be caused by the increased number of de novo mutations transmitted to offspring of older men. It has also been suggested that the associations are confounded by a genetic liability for psychiatric disorders in parents. The aim of this study was to indirectly test the confounding hypotheses by examining if there is a genetic component to advancing paternal age and if men with a genetic liability for psychiatric disorders have children at older ages.

Method

We examined the genetic component to advancing paternal age by utilizing the twin model in a cohort of male twins (N = 14 679). We also studied ages at childbirth in men with or without schizophrenia, bipolar disorder and/or autism spectrum disorder. Ages were examined in: (1) healthy men, (2) affected men, (3) healthy men with an affected sibling, (4) men with healthy spouses, (5) men with affected spouses, and (6) men with healthy spouses with an affected sibling.

Results

The twin analyses showed that late fatherhood is under genetic influence (heritability = 0.33). However, affected men or men with affected spouses did not have children at older ages. The same was found for healthy individuals with affected siblings. Instead, these men were generally having children at younger ages.

Conclusion

Although there is a genetic component influencing late fatherhood, our data suggest that the associations are not explained by psychiatric disorders or a genetic liability for psychiatric disorders in the parent.

Keywords

Autismbipolar disorderde novo mutationsfamilial confoundingheritabilitypaternal ageschizophreniasibling comparisontwin model
Type
Original Articles
Information
Psychological Medicine , Volume 46 , Issue 14 , October 2016 , pp. 2981 - 2988
Copyright
Copyright © Cambridge University Press 2016 

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References

Boker, S, Neale, M, Maes, H, Wilde, M, Spiegel, M, Brick, T, Spies, J, Estabrook, R, Kenny, S, Bates, T, Mehta, P, Fox, J (2011). OpenMx: an open source extended structural equation modeling framework. Psychometrika 76, 306–317.CrossRefGoogle ScholarPubMed
Byrne, M, Agerbo, E, Ewald, H, Eaton, WW, Mortensen, PB (2003). Parental age and risk of schizophrenia: a case-control study. Archives of General Psychiatry 60, 673–678.Google Scholar
Croen, LA, Najjar, DV, Fireman, B, Grether, JK (2007). Maternal and paternal age and risk of autism spectrum disorders. Archives of Pediatrics and Adolescent Medicine 161, 334–340.CrossRefGoogle ScholarPubMed
Crow, JF (2000). The origins, patterns and implications of human spontaneous mutation. Nature Reviews Genetics 1, 40–47.Google Scholar
Curley, JP, Mashoodh, R, Champagne, FA (2011). Epigenetics and the origins of paternal effects. Hormones and Behavior 59, 306–314.CrossRefGoogle ScholarPubMed
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. American Journal of Epidemiology 168, 1268–1276.CrossRefGoogle ScholarPubMed
Ek, M, Wicks, S, Svensson, AC, Idring, S, Dalman, C (2014). Advancing paternal age and schizophrenia: the impact of delayed fatherhood. Schizophrenia Bulletin 41, 708–714.Google Scholar
El-Saadi, O, Pedersen, CB, McNeil, TF, Saha, S, Welham, J, O'Callaghan, E, Cantor-Graae, E, Chant, D, Mortensen, PB, McGrath, J (2004). Paternal and maternal age as risk factors for psychosis: findings from Denmark, Sweden and Australia. Schizophrenia Research 67, 227–236.Google Scholar
Frans, EM, McGrath, JJ, Sandin, S, Lichtenstein, P, Reichenberg, A, Langstrom, N, Hultman, CM (2011). Advanced paternal and grandpaternal age and schizophrenia: a three-generation perspective. Schizophrenia Research 133, 120–124.Google Scholar
Frans, EM, Sandin, S, Reichenberg, A, Langstrom, N, Lichtenstein, P, McGrath, JJ, Hultman, CM (2013). Autism risk across generations: a population-based study of advancing grandpaternal and paternal age. JAMA Psychiatry 70, 516–521.CrossRefGoogle ScholarPubMed
Frans, EM, Sandin, S, Reichenberg, A, Lichtenstein, P, Langstrom, N, Hultman, CM (2008). Advancing paternal age and bipolar disorder. Archives of General Psychiatry 65, 1034–1040.Google Scholar
Granville-Grossman, KL (1966). Parental age and schizophrenia. British Journal of Psychiatry 112, 899–905.Google Scholar
Hultman, CM, Sandin, S, Levine, SZ, Lichtenstein, P, Reichenberg, A (2011). Advancing paternal age and risk of autism: new evidence from a population-based study and a meta-analysis of epidemiological studies. Molecular Psychiatry 16, 1203–1212.Google Scholar
Idring, S, Magnusson, C, Lundberg, M, Ek, M, Rai, D, Svensson, AC, Dalman, C, Karlsson, H, Lee, BK (2014). Parental age and the risk of autism spectrum disorders: findings from a Swedish population-based cohort. International Journal of Epidemiology 43, 107–115.Google Scholar
Lopez-Castroman, J (2014). Young maternal age and old paternal age induce similar risk of mental disorders in offspring. Evidence Based Mental Health 17, 100–100.Google Scholar
Lopez-Castroman, J, Gomez, 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. Schizophrenia Research 116, 184–190.Google Scholar
Ludvigsson, JF, Andersson, E, Ekbom, A, Feychting, M, Kim, JL, Reuterwall, C, Heurgren, M, Olausson, PO (2011). External review and validation of the Swedish national inpatient register. BMC Public Health 11, 1.Google Scholar
Magnusson, PK, Almqvist, C, Rahman, I, Ganna, A, Viktorin, A, Walum, H, Halldner, L, Lundstrom, S, Ullen, F, Langstrom, N, Larsson, H, Nyman, A, Gumpert, CH, Rastam, M, Anckarsater, H, Cnattingius, S, Johannesson, M, Ingelsson, E, Klareskog, L, de Faire, U, Pedersen, NL, Lichtenstein, P (2013). The Swedish Twin Registry: establishment of a biobank and other recent developments. Twin Research and Human Genetics 16, 317–329.Google Scholar
Malaspina, D, Harlap, S, Fennig, S, Heiman, D, Nahon, D, Feldman, D, Susser, ES (2001). Advancing paternal age and the risk of schizophrenia. Archives of General Psychiatry 58, 361–367.CrossRefGoogle ScholarPubMed
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. Psychological Medicine 40, 477–485.CrossRefGoogle ScholarPubMed
Neale, MC, Cardon, LR (1992). Methodology for Genetic Studies of Twins and Families. Dordrecht, The Netherlands: Kluwer Academic.Google Scholar
Petersen, L, Mortensen, PB, Pedersen, CB (2011). Paternal age at birth of first child and risk of schizophrenia. American Journal of Psychiatry 168, 82–88.CrossRefGoogle ScholarPubMed
Power, RA, Kyaga, S, Uher, R, MacCabe, JH, Langstrom, N, Landen, M, McGuffin, P, Lewis, CM, Lichtenstein, P, Svensson, AC (2013). Fecundity of patients with schizophrenia, autism, bipolar disorder, depression, anorexia nervosa, or substance abuse vs their unaffected siblings. JAMA Psychiatry 70, 22–30.CrossRefGoogle ScholarPubMed
Purcell, S (2002). Variance components models for gene-environment interaction in twin analysis. Twin Research: the Official Journal of the International Society for Twin Studies 5, 554–571.CrossRefGoogle ScholarPubMed
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. Archives of General Psychiatry 63, 1026–1032.Google Scholar
Sandin, S, Schendel, D, Magnusson, P, Hultman, C, Suren, P, Susser, E, Grønborg, T, Gissler, M, Gunnes, N, Gross, R (2015). Autism risk associated with parental age and with increasing difference in age between the parents. Molecular Psychiatry 21, 693–670.Google ScholarPubMed
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, 1070.Google Scholar
Statistics Sweden (2011). Multi-generation register 2010 – A description of contents and quality. In Population and Welfare Statistics. Statistics Sweden: Örebro.Google Scholar
Svensson, AC, Lichtenstein, P, Sandin, S, Hultman, CM (2007). Fertility of first-degree relatives of patients with schizophrenia: a three generation perspective. Schizophrenia Research 91, 238–245.Google Scholar
Thornberry, TP, Smith, CA, Howard, GJ (1997). Risk factors for teenage fatherhood. Journal of Marriage and Family 59, 505–522.Google Scholar
Toriello, HV, Meck, JM (2008). Statement on guidance for genetic counseling in advanced paternal age. Genetics in Medicine 10, 457–460.Google Scholar
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