The SNP-set based association study identifies ITGA1 as a susceptibility gene of attention-deficit/hyperactivity disorder in Han Chinese

• DOI: 10.1038/tp.2017.156
• Publication Date: 2017-08-15T13:42:08Z
• Authors: L Liu; L Zhang; H M Li; Z R Wang; X F Xie; J P Mei; J L Jin; J Shi; L Sun; S C Li; Y L Tan; L Yang; J Wang; H M Yang; Q J Qian; Y F Wang
• Keywords: Genome-wide Association Study; SNP; Genetic Association; Candidate gene; SNP genotyping; SNP array

Genome-wide association studies, which detect the between single-nucleotide polymorphisms (SNPs) and disease susceptibility, have been extensively applied to study attention-deficit/hyperactivity disorder (ADHD), but genome-wide significant associations not found yet. Genetic heterogeneity insufficient genomic coverage may account for missing heritability. We performed a two-stage ADHD in Han Chinese population. In discovery stage, 1033 patients 950 healthy controls were genotyped using both Affymetrix Genome-Wide Human SNP Array 6.0 Illumina Infinium HumanExome BeadChip. The SNPs combined generate powerful set with better especially nonsynonymous variants. addition of single SNPs, we collected adjacent as sets, determined by either genes or successive sliding windows, evaluate their synergetic effect. candidate susceptibility further replicated an independent cohort 1441 1447 controls. No gene-based sets be associated ADHD. However, two continuous windows located ITGA1 (P-value=8.33E−7 P-value=8.43E−7) significant. quantitative trait analyses also demonstrated core symptoms executive functions. was validated follow-up replications four selected SNPs: rs1979398 (P-value=2.64E−6), rs16880453 (P-value=3.58E−4), rs1531545 (P-value=7.62E−4) rs4074793 (P-value=2.03E−4). Our results suggest that genetic variants involved etiology SNP-set based analysis is promising strategy detection underlying risk factors.