A genome-wide scan for common alleles affecting risk for autism

By R. Anney, L. Klei, D. Pinto, R. Regan, J. Conroy, Tiago R. Magalhães, Catarina T. Correia, B. Abrahams, N. Sykes, A. Pagnamenta and 156 more. Human Molecular Genetics, 2010

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Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10−8. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10−8 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.

Subfields: Cognitive Neuroscience, Genetics

View Paper: https://www.semanticscholar.org/paper/3a96d1b538a3cddfcc7c17e0b67b0a504b8bdbfe

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Citations in the corpus

Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism. (2011, methodology): “, 2009),MACROD2 (Anney et al., 2010),CDH9 andCDH10 (Wang et al.”
Altered Structural Brain Connectivity in Healthy Carriers of the Autism Risk Gene, CNTNAP2 (2011, neutral): “Studies using this method have already been conducted on another autism risk gene (Kohannim et al., in review) that was a top hit in a genome-wide scan for risk alleles (Anney et al., 2010).”
The human splicing code reveals new insights into the genetic determinants of disease (2014, background): “Common genetic variants may also have an effect in ASD, but few studies replicate the same loci (39).”
Convergence of Genes and Cellular Pathways Dysregulated in Autism Spectrum Disorders (2014, background): “The second phase was divided in two stages; the results of stage 1, involving the first half of the families, were published in 2010.(6,20) In stage 2, we genotyped the remaining families (n 1⁄4 1,604) for a total of over 2,845 families and performed genomewide CNV (this study) and association studi”
Research review: Polygenic methods and their application to psychiatric traits. (2014, background): “…bipolar disorder, major depressive disorder (MDD), autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD; e.g. Anney et al., 2010; The International Schizophrenia Consortium (ISC), 2009; Neale et al., 2010; Sklar et al., 2008; Sullivan et al., 2009); showed a…”