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

作者：Anney Richard; Klei Lambertus; Pinto Dalila; Regan Regina; Conroy Judith; Magalhaes Tiago R; Correia Catarina; Abrahams Brett S; Sykes Nuala; Pagnamenta Alistair T; Almeida Joana; Bacchelli Elena; Bailey Anthony J; Baird Gillian; Battaglia Agatino; Berney Tom; Bolshakova Nadia; Boelte Sven; Bolton Patrick F; Bourgeron Thomas; Brennan Sean; Brian Jessica; Carson Andrew R; Casallo Guillermo; Casey Jillian; Chu Su H; Cochrane Lynne; Corsello Christina

来源：Human Molecular Genetics, 2010, 19(20): 4072-4082.

DOI：10.1093/hmg/ddq307

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 x 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 x 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.

• 出版日期2010-10-15