How rare and common risk variation jointly affect liability for autism spectrum disorder / Lambertus KLEI in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 66 p. Titre : How rare and common risk variation jointly affect liability for autism spectrum disorder Type de document : texte imprimé Auteurs : Lambertus KLEI, Auteur ; Lora Lee MCCLAIN, Auteur ; Behrang MAHJANI, Auteur ; Klea PANAYIDOU, Auteur ; Silvia DE RUBEIS, Auteur ; Anna-Carin Säll GRAHNAT, Auteur ; Gun KARLSSON, Auteur ; Yanchun LU, Auteur ; Nadine MELHEM, Auteur ; Xiu XU, Auteur ; Abraham REICHENBERG, Auteur ; Sven SANDIN, Auteur ; Christina M. HULTMAN, Auteur ; Joseph D. BUXBAUM, Auteur ; Kathryn ROEDER, Auteur ; Bernie DEVLIN, Auteur Article en page(s) : 66 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  De novo mutation  Genomic-Best Linear Unbiased Prediction (G-BLUP)  Liability  Polygenic risk score Index. décimale : PER Périodiques Résumé : BACKGROUND: Genetic studies have implicated rare and common variations in liability for autism spectrum disorder (ASD). Of the discovered risk variants, those rare in the population invariably have large impact on liability, while common variants have small effects. Yet, collectively, common risk variants account for the majority of population-level variability. How these rare and common risk variants jointly affect liability for individuals requires further study. METHODS: To explore how common and rare variants jointly affect liability, we assessed two cohorts of ASD families characterized for rare and common genetic variations (Simons Simplex Collection and Population-Based Autism Genetics and Environment Study). We analyzed data from 3011 affected subjects, as well as two cohorts of unaffected individuals characterized for common genetic variation: 3011 subjects matched for ancestry to ASD subjects and 11,950 subjects for estimating allele frequencies. We used genetic scores, which assessed the relative burden of common genetic variation affecting risk of ASD (henceforth "burden"), and determined how this burden was distributed among three subpopulations: ASD subjects who carry a potentially damaging variant implicated in risk of ASD ("PDV carriers"); ASD subjects who do not ("non-carriers"); and unaffected subjects who are assumed to be non-carriers. RESULTS: Burden harbored by ASD subjects is stochastically greater than that harbored by control subjects. For PDV carriers, their average burden is intermediate between non-carrier ASD and control subjects. Both carrier and non-carrier ASD subjects have greater burden, on average, than control subjects. The effects of common and rare variants likely combine additively to determine individual-level liability. LIMITATIONS: Only 305 ASD subjects were known PDV carriers. This relatively small subpopulation limits this study to characterizing general patterns of burden, as opposed to effects of specific PDVs or genes. Also, a small fraction of subjects that are categorized as non-carriers could be PDV carriers. CONCLUSIONS: Liability arising from common and rare risk variations likely combines additively to determine risk of any individual diagnosed with ASD. On average, ASD subjects carry a substantial burden of common risk variation, even if they also carry a rare PDV affecting risk. En ligne : http://dx.doi.org/10.1186/s13229-021-00466-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] How rare and common risk variation jointly affect liability for autism spectrum disorder [texte imprimé] / Lambertus KLEI, Auteur ; Lora Lee MCCLAIN, Auteur ; Behrang MAHJANI, Auteur ; Klea PANAYIDOU, Auteur ; Silvia DE RUBEIS, Auteur ; Anna-Carin Säll GRAHNAT, Auteur ; Gun KARLSSON, Auteur ; Yanchun LU, Auteur ; Nadine MELHEM, Auteur ; Xiu XU, Auteur ; Abraham REICHENBERG, Auteur ; Sven SANDIN, Auteur ; Christina M. HULTMAN, Auteur ; Joseph D. BUXBAUM, Auteur ; Kathryn ROEDER, Auteur ; Bernie DEVLIN, Auteur . - 66 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 66 p. Mots-clés : Autism spectrum disorder  De novo mutation  Genomic-Best Linear Unbiased Prediction (G-BLUP)  Liability  Polygenic risk score Index. décimale : PER Périodiques Résumé : BACKGROUND: Genetic studies have implicated rare and common variations in liability for autism spectrum disorder (ASD). Of the discovered risk variants, those rare in the population invariably have large impact on liability, while common variants have small effects. Yet, collectively, common risk variants account for the majority of population-level variability. How these rare and common risk variants jointly affect liability for individuals requires further study. METHODS: To explore how common and rare variants jointly affect liability, we assessed two cohorts of ASD families characterized for rare and common genetic variations (Simons Simplex Collection and Population-Based Autism Genetics and Environment Study). We analyzed data from 3011 affected subjects, as well as two cohorts of unaffected individuals characterized for common genetic variation: 3011 subjects matched for ancestry to ASD subjects and 11,950 subjects for estimating allele frequencies. We used genetic scores, which assessed the relative burden of common genetic variation affecting risk of ASD (henceforth "burden"), and determined how this burden was distributed among three subpopulations: ASD subjects who carry a potentially damaging variant implicated in risk of ASD ("PDV carriers"); ASD subjects who do not ("non-carriers"); and unaffected subjects who are assumed to be non-carriers. RESULTS: Burden harbored by ASD subjects is stochastically greater than that harbored by control subjects. For PDV carriers, their average burden is intermediate between non-carrier ASD and control subjects. Both carrier and non-carrier ASD subjects have greater burden, on average, than control subjects. The effects of common and rare variants likely combine additively to determine individual-level liability. LIMITATIONS: Only 305 ASD subjects were known PDV carriers. This relatively small subpopulation limits this study to characterizing general patterns of burden, as opposed to effects of specific PDVs or genes. Also, a small fraction of subjects that are categorized as non-carriers could be PDV carriers. CONCLUSIONS: Liability arising from common and rare risk variations likely combines additively to determine risk of any individual diagnosed with ASD. On average, ASD subjects carry a substantial burden of common risk variation, even if they also carry a rare PDV affecting risk. En ligne : http://dx.doi.org/10.1186/s13229-021-00466-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Parental and Perinatal Risk Factors for Autism: Epidemiological Findings and Potential Mechanisms / Sven SANDIN

Public ISBD in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM Titre : Parental and Perinatal Risk Factors for Autism: Epidemiological Findings and Potential Mechanisms Type de document : texte imprimé Auteurs : Sven SANDIN, Auteur ; Alexander KOLEVZON, Auteur ; Stephen Z. LEVINE, Auteur ; Christina M. HULTMAN, Auteur ; Abraham REICHENBERG, Auteur Année de publication : 2013 Importance : p.195-202 Langues : Anglais (eng) Index. décimale : SCI-D SCI-D - Neurosciences Résumé : There is evidence that non-heritable familial pre- or perinatal factors play a role in the etiology of autism and autism spectrum disorders (ASD). According to current evidence from epidemiological studies, two groups of factors show a consistent relationship with ASD: advancing parental age and preterm birth and intrauterine growth restriction. Using a systematic review and meta-analysis of epidemiological studies incorporating a comprehensive assessment of risk factors, we have examined the evidence for an association between advancing parental age, low birth weight, preterm birth and being born small for gestational age, and risk for ASD in the offspring. Advancing maternal age (35 or older), and paternal age (40 or older), show a consistent relationship with ASD. Current evidence also supports a relationship between low birth weight (lt; 2,500 grams), preterm birth (lt; 37 weeks) and being born small for gestational age, and ASD. Future research should continue to examine these variables using large, population-based cohorts in order to offer a more refined modeling of risk and potential confounders, and to attempt to distinguish between autism and spectrum disorders. Identifying common and unique risk factors may be important to understand shared and non-shared etiologies. Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=189 in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM Parental and Perinatal Risk Factors for Autism: Epidemiological Findings and Potential Mechanisms [texte imprimé] / Sven SANDIN, Auteur ; Alexander KOLEVZON, Auteur ; Stephen Z. LEVINE, Auteur ; Christina M. HULTMAN, Auteur ; Abraham REICHENBERG, Auteur . - 2013 . - p.195-202. Langues : Anglais (eng) Index. décimale : SCI-D SCI-D - Neurosciences Résumé : There is evidence that non-heritable familial pre- or perinatal factors play a role in the etiology of autism and autism spectrum disorders (ASD). According to current evidence from epidemiological studies, two groups of factors show a consistent relationship with ASD: advancing parental age and preterm birth and intrauterine growth restriction. Using a systematic review and meta-analysis of epidemiological studies incorporating a comprehensive assessment of risk factors, we have examined the evidence for an association between advancing parental age, low birth weight, preterm birth and being born small for gestational age, and risk for ASD in the offspring. Advancing maternal age (35 or older), and paternal age (40 or older), show a consistent relationship with ASD. Current evidence also supports a relationship between low birth weight (lt; 2,500 grams), preterm birth (lt; 37 weeks) and being born small for gestational age, and ASD. Future research should continue to examine these variables using large, population-based cohorts in order to offer a more refined modeling of risk and potential confounders, and to attempt to distinguish between autism and spectrum disorders. Identifying common and unique risk factors may be important to understand shared and non-shared etiologies. Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=189

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Prevalence and phenotypic impact of rare potentially damaging variants in autism spectrum disorder / Behrang MAHJANI in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 65 p. Titre : Prevalence and phenotypic impact of rare potentially damaging variants in autism spectrum disorder Type de document : texte imprimé Auteurs : Behrang MAHJANI, Auteur ; Silvia DE RUBEIS, Auteur ; Christina GUSTAVSSON MAHJANI, Auteur ; Maureen MULHERN, Auteur ; Xiu XU, Auteur ; Lambertus KLEI, Auteur ; F. Kyle SATTERSTROM, Auteur ; Jack FU, Auteur ; Michael E. TALKOWSKI, Auteur ; Abraham REICHENBERG, Auteur ; Sven SANDIN, Auteur ; Christina M. HULTMAN, Auteur ; Dorothy E. GRICE, Auteur ; Kathryn ROEDER, Auteur ; Bernie DEVLIN, Auteur ; Joseph D. BUXBAUM, Auteur Article en page(s) : 65 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Copy number variant  Intellectual disability  Pages  Single nucleotide variant  Whole exome sequencing  that they have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: The Autism Sequencing Consortium identified 102 high-confidence autism spectrum disorder (ASD) genes, showing that individuals with ASD and with potentially damaging single nucleotide variation (pdSNV) in these genes had lower cognitive levels and delayed age at walking, when compared to ASD participants without pdSNV. Here, we made use of a Swedish sample of individuals with ASD (called PAGES, for Population-Based Autism Genetics & Environment Study) to evaluate the frequency of pdSNV and their impact on medical and psychiatric phenotypes, using an epidemiological frame and universal health reporting. We then combine findings with those for potentially damaging copy number variation (pdCNV). METHODS: SNV and CNV calls were generated from whole-exome sequencing and chromosome microarray data, respectively. Birth and medical register data were used to collect phenotypes. RESULTS: Of 808 individuals assessed by sequencing, 69 (9%) had pdSNV in the 102 ASC genes, and 144 (18%) had pdSNV in the 102 ASC genes or in a larger set of curated neurodevelopmental genes (from the Deciphering Developmental Disorders study, the gene2phenotype database, and the Radboud University gene lists). Three or more individuals had pdSNV in GRIN2B, POGZ, SATB1, DYNC1H1, SCN8A, or CREBBP. In comparison, out of the 996 individuals from whom CNV were called, 105 (11%) carried one or more pdCNV, including four or more individuals with CNV in the recurrent 15q11q13, 22q11.2, and 16p11.2 loci. Carriers of pdSNV were more likely to have intellectual disability (ID) and epilepsy, while carriers of pdCNV showed increased rates of congenital anomalies and scholastic skill disorders. Carriers of either pdSNV or pdCNV were more likely to have ID, scholastic skill disorders, and epilepsy. LIMITATIONS: The cohort only included individuals with autistic disorder, the more severe form of ASD, and phenotypes are defined from medical registers. Not all genes studied are definitively ASD genes, and we did not have de novo information to aid in classification. CONCLUSIONS: In this epidemiological sample, rare pdSNV were more common than pdCNV and the combined yield of potentially damaging variation was substantial at 27%. The results provide compelling rationale for the use of high-throughout sequencing as part of routine clinical workup for ASD and support the development of precision medicine in ASD. En ligne : http://dx.doi.org/10.1186/s13229-021-00465-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Prevalence and phenotypic impact of rare potentially damaging variants in autism spectrum disorder [texte imprimé] / Behrang MAHJANI, Auteur ; Silvia DE RUBEIS, Auteur ; Christina GUSTAVSSON MAHJANI, Auteur ; Maureen MULHERN, Auteur ; Xiu XU, Auteur ; Lambertus KLEI, Auteur ; F. Kyle SATTERSTROM, Auteur ; Jack FU, Auteur ; Michael E. TALKOWSKI, Auteur ; Abraham REICHENBERG, Auteur ; Sven SANDIN, Auteur ; Christina M. HULTMAN, Auteur ; Dorothy E. GRICE, Auteur ; Kathryn ROEDER, Auteur ; Bernie DEVLIN, Auteur ; Joseph D. BUXBAUM, Auteur . - 65 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 65 p. Mots-clés : Autism spectrum disorder  Copy number variant  Intellectual disability  Pages  Single nucleotide variant  Whole exome sequencing  that they have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: The Autism Sequencing Consortium identified 102 high-confidence autism spectrum disorder (ASD) genes, showing that individuals with ASD and with potentially damaging single nucleotide variation (pdSNV) in these genes had lower cognitive levels and delayed age at walking, when compared to ASD participants without pdSNV. Here, we made use of a Swedish sample of individuals with ASD (called PAGES, for Population-Based Autism Genetics & Environment Study) to evaluate the frequency of pdSNV and their impact on medical and psychiatric phenotypes, using an epidemiological frame and universal health reporting. We then combine findings with those for potentially damaging copy number variation (pdCNV). METHODS: SNV and CNV calls were generated from whole-exome sequencing and chromosome microarray data, respectively. Birth and medical register data were used to collect phenotypes. RESULTS: Of 808 individuals assessed by sequencing, 69 (9%) had pdSNV in the 102 ASC genes, and 144 (18%) had pdSNV in the 102 ASC genes or in a larger set of curated neurodevelopmental genes (from the Deciphering Developmental Disorders study, the gene2phenotype database, and the Radboud University gene lists). Three or more individuals had pdSNV in GRIN2B, POGZ, SATB1, DYNC1H1, SCN8A, or CREBBP. In comparison, out of the 996 individuals from whom CNV were called, 105 (11%) carried one or more pdCNV, including four or more individuals with CNV in the recurrent 15q11q13, 22q11.2, and 16p11.2 loci. Carriers of pdSNV were more likely to have intellectual disability (ID) and epilepsy, while carriers of pdCNV showed increased rates of congenital anomalies and scholastic skill disorders. Carriers of either pdSNV or pdCNV were more likely to have ID, scholastic skill disorders, and epilepsy. LIMITATIONS: The cohort only included individuals with autistic disorder, the more severe form of ASD, and phenotypes are defined from medical registers. Not all genes studied are definitively ASD genes, and we did not have de novo information to aid in classification. CONCLUSIONS: In this epidemiological sample, rare pdSNV were more common than pdCNV and the combined yield of potentially damaging variation was substantial at 27%. The results provide compelling rationale for the use of high-throughout sequencing as part of routine clinical workup for ASD and support the development of precision medicine in ASD. En ligne : http://dx.doi.org/10.1186/s13229-021-00465-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

The International Collaboration for Autism Registry Epidemiology (iCARE): Multinational Registry-Based Investigations of Autism Risk Factors and Trends / Diana SCHENDEL in Journal of Autism and Developmental Disorders, 43-11 (November 2013)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 43-11 (November 2013) . - p.2650-2663 Titre : The International Collaboration for Autism Registry Epidemiology (iCARE): Multinational Registry-Based Investigations of Autism Risk Factors and Trends Type de document : texte imprimé Auteurs : Diana SCHENDEL, Auteur ; Michaeline BRESNAHAN, Auteur ; Kim W. CARTER, Auteur ; Richard W. FRANCIS, Auteur ; Mika GISSLER, Auteur ; Therese K. GRONBORG, Auteur ; Raz GROSS, Auteur ; Nina GUNNES, Auteur ; Mady HORNIG, Auteur ; Christina M. HULTMAN, Auteur ; Amanda LANGRIDGE, Auteur ; Marlene B. LAURITSEN, Auteur ; Helen LEONARD, Auteur ; Erik T. PARNER, Auteur ; Abraham REICHENBERG, Auteur ; Sven SANDIN, Auteur ; Andre SOURANDER, Auteur ; Camilla STOLTENBERG, Auteur ; Auli SUOMINEN, Auteur ; PÃ¥l SUREN, Auteur ; Ezra SUSSER, Auteur Article en page(s) : p.2650-2663 Langues : Anglais (eng) Mots-clés : Autism  Epidemiology  Study methods  Risk factors  Multinational Index. décimale : PER Périodiques Résumé : The International Collaboration for Autism Registry Epidemiology (iCARE) is the first multinational research consortium (Australia, Denmark, Finland, Israel, Norway, Sweden, USA) to promote research in autism geographical and temporal heterogeneity, phenotype, family and life course patterns, and etiology. iCARE devised solutions to challenges in multinational collaboration concerning data access security, confidentiality and management. Data are obtained by integrating existing national or state-wide, population-based, individual-level data systems and undergo rigorous harmonization and quality control processes. Analyses are performed using database federation via a computational infrastructure with a secure, web-based, interface. iCARE provides a unique, unprecedented resource in autism research that will significantly enhance the ability to detect environmental and genetic contributions to the causes and life course of autism. En ligne : http://dx.doi.org/10.1007/s10803-013-1815-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=217 [article] The International Collaboration for Autism Registry Epidemiology (iCARE): Multinational Registry-Based Investigations of Autism Risk Factors and Trends [texte imprimé] / Diana SCHENDEL, Auteur ; Michaeline BRESNAHAN, Auteur ; Kim W. CARTER, Auteur ; Richard W. FRANCIS, Auteur ; Mika GISSLER, Auteur ; Therese K. GRONBORG, Auteur ; Raz GROSS, Auteur ; Nina GUNNES, Auteur ; Mady HORNIG, Auteur ; Christina M. HULTMAN, Auteur ; Amanda LANGRIDGE, Auteur ; Marlene B. LAURITSEN, Auteur ; Helen LEONARD, Auteur ; Erik T. PARNER, Auteur ; Abraham REICHENBERG, Auteur ; Sven SANDIN, Auteur ; Andre SOURANDER, Auteur ; Camilla STOLTENBERG, Auteur ; Auli SUOMINEN, Auteur ; PÃ¥l SUREN, Auteur ; Ezra SUSSER, Auteur . - p.2650-2663. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 43-11 (November 2013) . - p.2650-2663 Mots-clés : Autism  Epidemiology  Study methods  Risk factors  Multinational Index. décimale : PER Périodiques Résumé : The International Collaboration for Autism Registry Epidemiology (iCARE) is the first multinational research consortium (Australia, Denmark, Finland, Israel, Norway, Sweden, USA) to promote research in autism geographical and temporal heterogeneity, phenotype, family and life course patterns, and etiology. iCARE devised solutions to challenges in multinational collaboration concerning data access security, confidentiality and management. Data are obtained by integrating existing national or state-wide, population-based, individual-level data systems and undergo rigorous harmonization and quality control processes. Analyses are performed using database federation via a computational infrastructure with a secure, web-based, interface. iCARE provides a unique, unprecedented resource in autism research that will significantly enhance the ability to detect environmental and genetic contributions to the causes and life course of autism. En ligne : http://dx.doi.org/10.1007/s10803-013-1815-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=217

Trajectories leading to autism spectrum disorders are affected by paternal age: findings from two nationally representative twin studies / Sebastian LUNDSTROM in Journal of Child Psychology and Psychiatry, 51-7 (July 2010)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 51-7 (July 2010) . - p.850-856 Titre : Trajectories leading to autism spectrum disorders are affected by paternal age: findings from two nationally representative twin studies Type de document : texte imprimé Auteurs : Sebastian LUNDSTROM, Auteur ; Christopher GILLBERG, Auteur ; Henrik ANCKARSATER, Auteur ; Christina M. HULTMAN, Auteur ; Eva CARLSTROM, Auteur ; Abraham REICHENBERG, Auteur ; Jonathan MILL, Auteur ; Angelica RONALD, Auteur ; Robert PLOMIN, Auteur ; Maria RASTAM, Auteur ; Paul LICHTENSTEIN, Auteur ; Claire Margaret Alison HAWORTH, Auteur Année de publication : 2010 Article en page(s) : p.850-856 Langues : Anglais (eng) Mots-clés : Autism-spectrum-disorders paternal-age autistic-traits behavioral-genetics Index. décimale : PER Périodiques Résumé : Background: Despite extensive efforts, the causes of autism remain unknown. Advancing paternal age has been associated with various neurodevelopmental disorders. We aim to investigate three unresolved questions: (a) What is the association between paternal age and autism spectrum disorders (ASD)?; (b) Does paternal age moderate the genetic and environmental etiological factors for ASD? (c) Does paternal age affect normal variation in autistic-like traits? Methods: Two nationally representative twin studies from Sweden (n = 11, 122, assessed at age 9 or 12) and the UK (n = 13, 524, assessed at age 9) were used. Categorical and continuous measures of ASD, autistic-like traits and autistic similarity were calculated and compared over paternal age categories. Results: Both cohorts showed a strong association between paternal age and the risk for ASD. A U-shaped risk association could be discerned since the offspring of both the youngest and oldest fathers showed an elevation in the risk for ASD. Autistic similarity increased with advancing paternal age in both monozygotic and dizygotic twins. Both cohorts showed significantly higher autistic-like traits in the offspring of the youngest and oldest fathers. Conclusions: Phenomena associated with paternal age are clearly involved in the trajectories leading to autistic-like traits and ASD. Mechanisms influencing the trajectories might differ between older and younger fathers. Molecular genetic studies are now needed in order to further understand the association between paternal age and ASD, as well as normal variation in social, language, and repetitive behaviors in the general population. En ligne : http://dx.doi.org/10.1111/j.1469-7610.2010.02223.x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=102 [article] Trajectories leading to autism spectrum disorders are affected by paternal age: findings from two nationally representative twin studies [texte imprimé] / Sebastian LUNDSTROM, Auteur ; Christopher GILLBERG, Auteur ; Henrik ANCKARSATER, Auteur ; Christina M. HULTMAN, Auteur ; Eva CARLSTROM, Auteur ; Abraham REICHENBERG, Auteur ; Jonathan MILL, Auteur ; Angelica RONALD, Auteur ; Robert PLOMIN, Auteur ; Maria RASTAM, Auteur ; Paul LICHTENSTEIN, Auteur ; Claire Margaret Alison HAWORTH, Auteur . - 2010 . - p.850-856. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 51-7 (July 2010) . - p.850-856 Mots-clés : Autism-spectrum-disorders paternal-age autistic-traits behavioral-genetics Index. décimale : PER Périodiques Résumé : Background: Despite extensive efforts, the causes of autism remain unknown. Advancing paternal age has been associated with various neurodevelopmental disorders. We aim to investigate three unresolved questions: (a) What is the association between paternal age and autism spectrum disorders (ASD)?; (b) Does paternal age moderate the genetic and environmental etiological factors for ASD? (c) Does paternal age affect normal variation in autistic-like traits? Methods: Two nationally representative twin studies from Sweden (n = 11, 122, assessed at age 9 or 12) and the UK (n = 13, 524, assessed at age 9) were used. Categorical and continuous measures of ASD, autistic-like traits and autistic similarity were calculated and compared over paternal age categories. Results: Both cohorts showed a strong association between paternal age and the risk for ASD. A U-shaped risk association could be discerned since the offspring of both the youngest and oldest fathers showed an elevation in the risk for ASD. Autistic similarity increased with advancing paternal age in both monozygotic and dizygotic twins. Both cohorts showed significantly higher autistic-like traits in the offspring of the youngest and oldest fathers. Conclusions: Phenomena associated with paternal age are clearly involved in the trajectories leading to autistic-like traits and ASD. Mechanisms influencing the trajectories might differ between older and younger fathers. Molecular genetic studies are now needed in order to further understand the association between paternal age and ASD, as well as normal variation in social, language, and repetitive behaviors in the general population. En ligne : http://dx.doi.org/10.1111/j.1469-7610.2010.02223.x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=102

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