Assessing the impact of a combined analysis of four common low-risk genetic variants on autism risk / Jerome CARAYOL in Molecular Autism, (February 2010)  

Public ISBD [article]  inMolecular Autism > (February 2010) . - 11 p. Titre : Assessing the impact of a combined analysis of four common low-risk genetic variants on autism risk Type de document : Texte imprimé et/ou numérique Auteurs : Jerome CARAYOL, Auteur ; Geraldine DAWSON, Auteur ; Gerard SCHELLENBERG, Auteur ; Frederic TORES, Auteur ; Jörg HAGER, Auteur ; Andreas ZIEGLER, Auteur Année de publication : 2010 Article en page(s) : 11 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Background Autism is a complex disorder characterized by deficits involving communication, social interaction, and repetitive and restrictive patterns of behavior. Twin studies have shown that autism is strongly heritable, suggesting a strong genetic component. In other disease states with a complex etiology, such as type 2 diabetes, cancer and cardiovascular disease, combined analysis of multiple genetic variants in a genetic score has helped to identify individuals at high risk of disease. Genetic scores are designed to test for association of genetic markers with disease. Method The accumulation of multiple risk alleles markedly increases the risk of being affected, and compared with studying polymorphisms individually, it improves the identification of subgroups of individuals at greater risk. In the present study, we show that this approach can be applied to autism by specifically looking at a high-risk population of children who have siblings with autism. A two-sample study design and the generation of a genetic score using multiple independent genes were used to assess the risk of autism in a high-risk population. Results In both samples, odds ratios (ORs) increased significantly as a function of the number of risk alleles, with a genetic score of 8 being associated with an OR of 5.54 (95% confidence interval [CI] 2.45 to 12.49). The sensitivities and specificities for each genetic score were similar in both analyses, and the resultant area under the receiver operating characteristic curves were identical (0.59). Conclusions These results suggest that the accumulation of multiple risk alleles in a genetic score is a useful strategy for assessing the risk of autism in siblings of affected individuals, and may be better than studying single polymorphisms for identifying subgroups of individuals with significantly greater risk. En ligne : http://dx.doi.org/10.1186/2040-2392-1-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=102 [article] Assessing the impact of a combined analysis of four common low-risk genetic variants on autism risk [Texte imprimé et/ou numérique] / Jerome CARAYOL, Auteur ; Geraldine DAWSON, Auteur ; Gerard SCHELLENBERG, Auteur ; Frederic TORES, Auteur ; Jörg HAGER, Auteur ; Andreas ZIEGLER, Auteur . - 2010 . - 11 p. Langues : Anglais (eng) in Molecular Autism > (February 2010) . - 11 p. Index. décimale : PER Périodiques Résumé : Background Autism is a complex disorder characterized by deficits involving communication, social interaction, and repetitive and restrictive patterns of behavior. Twin studies have shown that autism is strongly heritable, suggesting a strong genetic component. In other disease states with a complex etiology, such as type 2 diabetes, cancer and cardiovascular disease, combined analysis of multiple genetic variants in a genetic score has helped to identify individuals at high risk of disease. Genetic scores are designed to test for association of genetic markers with disease. Method The accumulation of multiple risk alleles markedly increases the risk of being affected, and compared with studying polymorphisms individually, it improves the identification of subgroups of individuals at greater risk. In the present study, we show that this approach can be applied to autism by specifically looking at a high-risk population of children who have siblings with autism. A two-sample study design and the generation of a genetic score using multiple independent genes were used to assess the risk of autism in a high-risk population. Results In both samples, odds ratios (ORs) increased significantly as a function of the number of risk alleles, with a genetic score of 8 being associated with an OR of 5.54 (95% confidence interval [CI] 2.45 to 12.49). The sensitivities and specificities for each genetic score were similar in both analyses, and the resultant area under the receiver operating characteristic curves were identical (0.59). Conclusions These results suggest that the accumulation of multiple risk alleles in a genetic score is a useful strategy for assessing the risk of autism in siblings of affected individuals, and may be better than studying single polymorphisms for identifying subgroups of individuals with significantly greater risk. En ligne : http://dx.doi.org/10.1186/2040-2392-1-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=102

Autism risk assessment in siblings of affected children using sex-specific genetic scores / Jerome CARAYOL in Molecular Autism, (October 2011)  

Public ISBD [article]  inMolecular Autism > (October 2011) . - 8 p. Titre : Autism risk assessment in siblings of affected children using sex-specific genetic scores Type de document : Texte imprimé et/ou numérique Auteurs : Jerome CARAYOL, Auteur ; Gerard SCHELLENBERG, Auteur ; Beth DOMBROSKI, Auteur ; Emmanuelle GENIN, Auteur ; Francis ROUSSEAU, Auteur ; Geraldine DAWSON, Auteur Année de publication : 2011 Article en page(s) : 8 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND:The inheritance pattern in most cases of autism is complex. The risk of autism is increased in siblings of children with autism and previous studies have indicated that the level of risk can be further identified by the accumulation of multiple susceptibility single nucleotide polymorphisms (SNPs) allowing for the identification of a higher-risk subgroup among siblings. As a result of the sex difference in the prevalence of autism, we explored the potential for identifying sex-specific autism susceptibility SNPs in siblings of children with autism and the ability to develop a sex-specific risk assessment genetic scoring system.METHODS:SNPs were chosen from genes known to be associated with autism. These markers were evaluated using an exploratory sample of 480 families from the Autism Genetic Resource Exchange (AGRE) repository. A reproducibility index (RI) was proposed and calculated in all children with autism and in males and females separately. Differing genetic scoring models were then constructed to develop a sex-specific genetic score model designed to identify individuals with a higher risk of autism. The ability of the genetic scores to identify high-risk children was then evaluated and replicated in an independent sample of 351 affected and 90 unaffected siblings from families with at least 1 child with autism.RESULTS:We identified three risk SNPs that had a high RI in males, two SNPs with a high RI in females, and three SNPs with a high RI in both sexes. Using these results, genetic scoring models for males and females were developed which demonstrated a significant association with autism (P = 2.2 x 10-6 and 1.9 x 10-5, respectively).CONCLUSIONS:Our results demonstrate that individual susceptibility associated SNPs for autism may have important differential sex effects. We also show that a sex-specific risk score based on the presence of multiple susceptibility associated SNPs allow for the identification of subgroups of siblings of children with autism who have a significantly higher risk of autism. En ligne : http://dx.doi.org/10.1186/2040-2392-2-17 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=149 [article] Autism risk assessment in siblings of affected children using sex-specific genetic scores [Texte imprimé et/ou numérique] / Jerome CARAYOL, Auteur ; Gerard SCHELLENBERG, Auteur ; Beth DOMBROSKI, Auteur ; Emmanuelle GENIN, Auteur ; Francis ROUSSEAU, Auteur ; Geraldine DAWSON, Auteur . - 2011 . - 8 p. Langues : Anglais (eng) in Molecular Autism > (October 2011) . - 8 p. Index. décimale : PER Périodiques Résumé : BACKGROUND:The inheritance pattern in most cases of autism is complex. The risk of autism is increased in siblings of children with autism and previous studies have indicated that the level of risk can be further identified by the accumulation of multiple susceptibility single nucleotide polymorphisms (SNPs) allowing for the identification of a higher-risk subgroup among siblings. As a result of the sex difference in the prevalence of autism, we explored the potential for identifying sex-specific autism susceptibility SNPs in siblings of children with autism and the ability to develop a sex-specific risk assessment genetic scoring system.METHODS:SNPs were chosen from genes known to be associated with autism. These markers were evaluated using an exploratory sample of 480 families from the Autism Genetic Resource Exchange (AGRE) repository. A reproducibility index (RI) was proposed and calculated in all children with autism and in males and females separately. Differing genetic scoring models were then constructed to develop a sex-specific genetic score model designed to identify individuals with a higher risk of autism. The ability of the genetic scores to identify high-risk children was then evaluated and replicated in an independent sample of 351 affected and 90 unaffected siblings from families with at least 1 child with autism.RESULTS:We identified three risk SNPs that had a high RI in males, two SNPs with a high RI in females, and three SNPs with a high RI in both sexes. Using these results, genetic scoring models for males and females were developed which demonstrated a significant association with autism (P = 2.2 x 10-6 and 1.9 x 10-5, respectively).CONCLUSIONS:Our results demonstrate that individual susceptibility associated SNPs for autism may have important differential sex effects. We also show that a sex-specific risk score based on the presence of multiple susceptibility associated SNPs allow for the identification of subgroups of siblings of children with autism who have a significantly higher risk of autism. En ligne : http://dx.doi.org/10.1186/2040-2392-2-17 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=149

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