scholarly journals Older fathers' children have lower evolutionary fitness across four centuries and in four populations

2016 ◽  
Author(s):  
Ruben C. Arslan ◽  
Kai P. Willführ ◽  
Emma Frans ◽  
Karin J. H. Verweij ◽  
Mikko Myrskylä ◽  
...  
Keyword(s):  
De Novo ◽  
Child Survival ◽  
Genetic Load ◽  
Age Effects ◽  
Paternal Age ◽  
De Novo Mutations ◽  
Delayed Reproduction ◽  
Large Populations ◽  
Sibling Control ◽  
Control Study

Higher paternal age at offspring conception increases de novo genetic mutations (Kong et al., 2012). Based on evolutionary genetic theory we predicted that the offspring of older fathers would be less likely to survive and reproduce, i.e. have lower fitness. In a sibling control study, we find clear support for negative paternal age effects on offspring survival, mating and reproductive success across four large populations with an aggregate N > 1.3 million in main analyses. Compared to a sibling born when the father was 10 years younger, individuals had 4-13% fewer surviving children in the four populations. Three populations were pre-industrial (1670-1850) Western populations and showed a pattern of paternal age effects across the offspring's lifespan. In 20th-century Sweden, we found no negative paternal age effects on child survival or marriage odds. Effects survived tests for competing explanations, including maternal age and parental loss. To the extent that we succeeded in isolating a mutation-driven effect of paternal age, our results can be understood to show that de novo mutations reduce offspring fitness across populations and time. We can use this understanding to predict the effect of increasingly delayed reproduction on offspring genetic load, mortality and fertility.

scholarly journals Older fathers' children have lower evolutionary fitness across four centuries and in four populations

2017 ◽  
Vol 284 (1862) ◽  
pp. 20171562 ◽  
Author(s):  
Ruben C. Arslan ◽  
Kai P. Willführ ◽  
Emma M. Frans ◽  
Karin J. H. Verweij ◽  
Paul-Christian Bürkner ◽  
...  
Keyword(s):  
Reproductive Success ◽  
De Novo ◽  
Age Effects ◽  
Paternal Age ◽  
De Novo Mutations ◽  
Negative Effects ◽  
Older Parents ◽  
Plausible Model ◽  
Large Populations ◽  
Sibling Control

Higher paternal age at offspring conception increases de novo genetic mutations. Based on evolutionary genetic theory we predicted older fathers' children, all else equal, would be less likely to survive and reproduce, i.e. have lower fitness. In sibling control studies, we find support for negative paternal age effects on offspring survival and reproductive success across four large populations with an aggregate N > 1.4 million. Three populations were pre-industrial (1670–1850) Western populations and showed negative paternal age effects on infant survival and offspring reproductive success. In twentieth-century Sweden, we found minuscule paternal age effects on survival, but found negative effects on reproductive success. Effects survived tests for key competing explanations, including maternal age and parental loss, but effects varied widely over different plausible model specifications and some competing explanations such as diminishing paternal investment and epigenetic mutations could not be tested. We can use our findings to aid in predicting the effect increasingly older parents in today's society will have on their children's survival and reproductive success. To the extent that we succeeded in isolating a mutation-driven effect of paternal age, our results can be understood to show that de novo mutations reduce offspring fitness across populations and time periods.

scholarly journals Impact of Paternal Age at Conception on Human Health

2019 ◽  
Vol 65 (1) ◽  
pp. 146-152 ◽  
Author(s):  
Mathieu Simard ◽  
Catherine Laprise ◽  
Simon L Girard
Keyword(s):  
Maternal Age ◽  
De Novo ◽  
Autism Spectrum ◽  
Age Effect ◽  
Age Effects ◽  
Paternal Age ◽  
De Novo Mutations ◽  
Brain Functions ◽  
Offspring Health ◽  
Paternal Age Effect

Abstract BACKGROUND The effect of maternal age at conception on various aspects of offspring health is well documented and often discussed. We seldom hear about the paternal age effect on offspring health, although the link is now almost as solid as with maternal age. The causes behind this, however, are drastically different between males and females. CONTENT In this review article, we will first examine documented physiological changes linked to paternal age effect. We will start with all morphological aspects of the testis that have been shown to be altered with aging. We will then move on to all the parameters of spermatogenesis that are linked with paternal age at conception. The biggest part of this review will focus on genetic changes associated with paternal age effects. Several studies that have established a strong link between paternal age at conception and the rate of de novo mutations will be reviewed. We will next discuss paternal age effects associated with telomere length and try to better understand the seemingly contradictory results. Finally, severe diseases that affect brain functions and normal development have been associated with older paternal age at conception. In this context, we will discuss the cases of autism spectrum disorder and schizophrenia, as well as several childhood cancers. SUMMARY In many Western civilizations, the age at which parents have their first child has increased substantially in recent decades. It is important to summarize major health issues associated with an increased paternal age at conception to better model public health systems.

Schizophrenia Risk and Paternal Age: A Potential Role for De Novo Mutations in Schizophrenia Vulnerability Genes

CNS Spectrums ◽  
2002 ◽  
Vol 7 (1) ◽  
pp. 26-29 ◽  
Author(s):  
Dolores Malaspina ◽  
Alan Brown ◽  
Deborah Goetz ◽  
Nelly Alia-Klein ◽  
Jill Harkavy-Friedman ◽  
...  
Keyword(s):  
Human Population ◽  
Potential Role ◽  
De Novo ◽  
Paternal Age ◽  
Current Evidence ◽  
Parental Age ◽  
De Novo Mutations ◽  
New Mutations

ABSTRACTHow schizophrenia (SZ) is maintained at roughly 1% of the population despite diminished reproduction is one puzzle currently facing researchers. De novo mutations were first proposed over half a century ago as a source for new SZ genes. Current evidence linking advancing paternal age to SZ risk makes revisiting this hypothesis important. Advancing paternal age is the major source of new mutations in the human population. This article will examine potential mechanisms whereby parental age may impact new mutations, as well as review recent data supporting such a hypothesis.

scholarly journals Advancing paternal age and offspring violent offending: A sibling-comparison study

2012 ◽  
Vol 24 (3) ◽  
pp. 739-753 ◽  
Author(s):  
Ralf Kuja-Halkola ◽  
Yudi Pawitan ◽  
Brian M. D'Onofrio ◽  
Niklas Långström ◽  
Paul Lichtenstein
Keyword(s):  
Violent Crime ◽  
De Novo ◽  
Causal Effect ◽  
Paternal Age ◽  
De Novo Mutations ◽  
Criminal Convictions ◽  
Violent Offending ◽  
Genes And Environment ◽  
Life Course Persistent ◽  
Severe Psychopathology

AbstractChildren born to older fathers are at higher risk to develop severe psychopathology (e.g., schizophrenia and bipolar disorder), possibly because of increased de novo mutations during spermatogenesis with older paternal age. Because severe psychopathology is correlated with antisocial behavior, we examined possible associations between advancing paternal age and offspring violent offending. Interlinked Swedish national registers provided information on fathers' age at childbirth and violent criminal convictions in all offspring born from 1958 to 1979 (N= 2,359,921). We used ever committing a violent crime and number of violent crimes as indices of violent offending. The data included information on multiple levels; we compared differentially exposed siblings in within-family analyses to rigorously test causal influences. In the entire population, advancing paternal age predicted offspring violent crime according to both indices. Congruent with a causal effect, this association remained for rates of violent crime in within-family analyses. However, in within-family analyses, we found no association with ever committing a violent crime, suggesting that factors shared by siblings (genes and environment) confounded this association. Life-course persistent criminality has been proposed to have a partly biological etiology; our results agree with a stronger biological effect (i.e., de novo mutations) on persistent violent offending.

Risk of Psychiatric Illness From Advanced Paternal Age Is Not Predominantly From De Novo Mutations

2017 ◽  
Vol 72 (2) ◽  
pp. 96
Author(s):  
Jacob Gratten ◽  
Naomi R. Wray ◽  
Wouter J. Peyrot ◽  
John J. McGrath ◽  
Peter M. Visscher ◽  
...  
Keyword(s):  
Psychiatric Illness ◽  
De Novo ◽  
Paternal Age ◽  
De Novo Mutations ◽  
Advanced Paternal Age

scholarly journals Paternal age and sporadic schizophrenia: Evidence for de novo mutations

2002 ◽  
Vol 114 (3) ◽  
pp. 299-303 ◽  
Author(s):  
Dolores Malaspina ◽  
Cheryl Corcoran ◽  
Cherine Fahim ◽  
Ariela Berman ◽  
Jill Harkavy-Friedman ◽  
...  
Keyword(s):  
De Novo ◽  
Paternal Age ◽  
De Novo Mutations

Risk of psychiatric illness from advanced paternal age is not predominantly from de novo mutations

2016 ◽  
Vol 48 (7) ◽  
pp. 718-724 ◽  
Author(s):  
Jacob Gratten ◽  
Naomi R Wray ◽  
Wouter J Peyrot ◽  
John J McGrath ◽  
Peter M Visscher ◽  
...  
Keyword(s):  
Psychiatric Illness ◽  
De Novo ◽  
Paternal Age ◽  
De Novo Mutations ◽  
Advanced Paternal Age

scholarly journals Paternal-Age-Related de Novo Mutations and Risk for Five Disorders

2020 ◽  
Vol 75 (2) ◽  
pp. 104-105
Author(s):  
Jacob L. Taylor ◽  
Jean-Christophe P. G. Debost ◽  
Sarah U. Morton ◽  
Emilie M. Wigdor ◽  
Henrike O. Heyne ◽  
...  
Keyword(s):  
De Novo ◽  
Paternal Age ◽  
De Novo Mutations ◽  
Age Related

scholarly journals Paternal-age-related de novo mutations and risk for five disorders

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Jacob L. Taylor ◽  
Jean-Christophe P. G. Debost ◽  
Sarah U. Morton ◽  
Emilie M. Wigdor ◽  
Henrike O. Heyne ◽  
...  
Keyword(s):  
De Novo ◽  
Paternal Age ◽  
De Novo Mutations ◽  
Age Related

scholarly journals Mutation rates and the evolution of germline structure

2016 ◽  
Vol 371 (1699) ◽  
pp. 20150137 ◽  
Author(s):  
Aylwyn Scally
Keyword(s):  
Mutation Rate ◽  
De Novo ◽  
Active Role ◽  
Paternal Age ◽  
State Transitions ◽  
De Novo Mutations ◽  
Evolutionary Changes ◽  
Sequencing Studies ◽  
Paternal Age Effect ◽  
Stem Cell State

Genome sequencing studies of de novo mutations in humans have revealed surprising incongruities in our understanding of human germline mutation. In particular, the mutation rate observed in modern humans is substantially lower than that estimated from calibration against the fossil record, and the paternal age effect in mutations transmitted to offspring is much weaker than expected from our long-standing model of spermatogenesis. I consider possible explanations for these discrepancies, including evolutionary changes in life-history parameters such as generation time and the age of puberty, a possible contribution from undetected post-zygotic mutations early in embryo development, and changes in cellular mutation processes at different stages of the germline. I suggest a revised model of stem-cell state transitions during spermatogenesis, in which ‘dark’ gonial stem cells play a more active role than hitherto envisaged, with a long cycle time undetected in experimental observations. More generally, I argue that the mutation rate and its evolution depend intimately on the structure of the germline in humans and other primates. This article is part of the themed issue ‘Dating species divergences using rocks and clocks'.

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