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

2017 ◽  
Author(s):  
Jacob L. Taylor ◽  
Jean-Christophe P.G. Debost ◽  
Sarah U. Morton ◽  
Emilie M. Wigdor ◽  
Henrike O. Heyne ◽  
...  
Keyword(s):  
Developmental Disorders ◽  
De Novo ◽  
Autism Spectrum ◽  
National Registry ◽  
Paternal Age ◽  
De Novo Mutations ◽  
Single Nucleotide Variants ◽  
Advanced Paternal Age ◽  
Age Related ◽  
Rate Ratios

AbstractBackgroundThere are well-established epidemiologic associations between advanced paternal age and increased offspring risk for several psychiatric and developmental disorders. These associations are commonly attributed to age-related de novo mutations. However, the actual magnitude of risk conferred by age-related de novo mutations in the male germline is unknown. Quantifying this risk would clarify the clinical and public health significance of delayed paternity.MethodsUsing results from large, parent-child trio whole-exome-sequencing studies, we estimated the relationship between paternal-age-related de novo single nucleotide variants (dnSNVs) and offspring risk for five disorders: autism spectrum disorders (ASD), congenital heart disease (CHD), neurodevelopmental disorders with epilepsy (EPI), intellectual disability (ID), and schizophrenia (SCZ). Using Danish national registry data, we then investigated the degree to which the epidemiologic association between each disorder and advanced paternal age was consistent with the estimated role of de novo mutations.ResultsIncidence rate ratios comparing dnSNV-based risk to offspring of 45 versus 25-year-old fathers ranged from 1.05 (95% confidence interval 1.01–1.13) for SCZ to 1.29 (95% CI 1.13-1.68) for ID. Epidemiologic estimates of paternal age risk for CHD, ID and EPI were consistent with the dnSNV effect. However, epidemiologic effects for ASDs and SCZ significantly exceeded the risk that could be explained by dnSNVs alone (p<2e-4 for both comparisons).ConclusionIncreasing dnSNVs due to advanced paternal age confer a small amount of offspring risk for psychiatric and developmental disorders. For ASD and SCZ, epidemiologic associations with delayed paternity largely reflect factors that cannot be assumed to increase with age.

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 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.

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 Environmental carcinogens disproportionally mutate genes implicated in neurodevelopmental disorders

2021 ◽  
Author(s):  
Brennan H Baker ◽  
Shaoyi Zhang ◽  
Jeremy M Simon ◽  
Sarah M McLarnan ◽  
Wendy K Chung ◽  
...  
Keyword(s):  
Neurodevelopmental Disorders ◽  
Developmental Disorders ◽  
De Novo ◽  
Autism Spectrum ◽  
Disease Genes ◽  
Environmental Carcinogens ◽  
De Novo Mutations ◽  
New Paradigm ◽  
Disease Etiology ◽  
Neurodevelopmental Disease

De novo mutations contribute to a large proportion of sporadic psychiatric and developmental disorders, yet the potential role of environmental carcinogens as drivers of causal de novo mutations in neurodevelopmental disorders is poorly studied. We demonstrate that several mutagens, including polycyclic aromatic hydrocarbons (PAHs), disproportionately mutate genes related to neurodevelopmental disorders including autism spectrum disorders (ASD), schizophrenia, and attention deficit hyperactivity disorder (ADHD). Other disease genes including amyotrophic lateral sclerosis (ALS), Alzheimers disease, congenital heart disease, orofacial clefts, and coronary artery disease were generally not mutated more than expected. Our findings support a new paradigm of neurodevelopmental disease etiology driven by a contribution of environmentally induced rather than random mutations.

scholarly journals Integrated gene analyses of de novo mutations from 46,612 trios with autism and developmental disorders

2021 ◽  
Author(s):  
Tianyun Wang ◽  
Chang Kim ◽  
Trygve E. Bakken ◽  
Madelyn A. Gillentine ◽  
Barbara Henning ◽  
...  
Keyword(s):  
Developmental Disorders ◽  
De Novo ◽  
Autism Spectrum ◽  
Mutational Bias ◽  
De Novo Mutations ◽  
Cell Nuclei ◽  
Genetic Studies ◽  
Risk Genes ◽  
Functional Studies ◽  
Disease Subtypes

ABSTRACTMost genetic studies consider autism spectrum disorder (ASD) and developmental disorder (DD) separately despite overwhelming comorbidity and shared genetic etiology. Here we analyzed de novo mutations (DNMs) from 15,560 ASD (6,557 are new) and 31,052 DD trios independently and combined as broader neurodevelopmental disorders (NDD) using three models. We identify 615 candidate genes (FDR 5%, 189 potentially novel) by one or more models, including 138 reaching exome-wide significance (p < 3.64e-07) in all models. We find no evidence for ASD-specific genes in contrast to 18 genes significantly enriched for DD. There are 53 genes show particular mutational-bias including enrichments for missense (n=41) or truncating DNM (n=12). We find 22 genes with evidence of sex-bias including five X chromosome genes also with significant female burden (DDX3X, MECP2, SMC1A, WDR45, and HDAC8). NDD risk genes group into five functional networks associating with different brain developmental lineages based on single-cell nuclei transcriptomic data, which provides important insights into disease subtypes and future functional studies.

scholarly journals A Bibliometric Insight of Genetic Factors in ASD: Emerging Trends and New Developments

2020 ◽  
Vol 11 (1) ◽  
pp. 33
Author(s):  
Kang Wang ◽  
Weicheng Duan ◽  
Yijie Duan ◽  
Yuxin Yu ◽  
Xiuyi Chen ◽  
...  
Keyword(s):  
Genetic Factors ◽  
De Novo ◽  
Rapid Development ◽  
The United States ◽  
Research Area ◽  
Scientific Output ◽  
Autism Spectrum ◽  
De Novo Mutations ◽  
Emerging Trends ◽  
Genetic Abnormalities

Autism spectrum disorder (ASD) cases have increased rapidly in recent decades, which is associated with various genetic abnormalities. To provide a better understanding of the genetic factors in ASD, we assessed the global scientific output of the related studies. A total of 2944 studies published between 1997 and 2018 were included by systematic retrieval from the Web of Science (WoS) database, whose scientific landscapes were drawn and the tendencies and research frontiers were explored through bibliometric methods. The United States has been acting as a leading explorer of the field worldwide in recent years. The rapid development of high-throughput technologies and bioinformatics transferred the research method from the traditional classic method to a big data-based pipeline. As a consequence, the focused research area and tendency were also changed, as the contribution of de novo mutations in ASD has been a research hotspot in the past several years and probably will remain one into the near future, which is consistent with the current opinions of the major etiology of ASD. Therefore, more attention and financial support should be paid to the deciphering of the de novo mutations in ASD. Meanwhile, the effective cooperation of multi-research centers and scientists in different fields should be advocated in the next step of scientific research undertaken.

scholarly journals CACNA1D De Novo Mutations in Autism Spectrum Disorders Activate Cav1.3 L-Type Calcium Channels

2015 ◽  
Vol 77 (9) ◽  
pp. 816-822 ◽  
Author(s):  
Alexandra Pinggera ◽  
Andreas Lieb ◽  
Bruno Benedetti ◽  
Michaela Lampert ◽  
Stefania Monteleone ◽  
...  
Keyword(s):  
Autism Spectrum Disorders ◽  
Calcium Channels ◽  
De Novo ◽  
Autism Spectrum ◽  
De Novo Mutations ◽  
Spectrum Disorders
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