Genome-wide copy number variation study associates metabotropic glutamate receptor gene networks with attention deficit hyperactivity disorder

摘要

ADHD is a common neuropsychiatric disorder with heritability estimates as high as 90% (refs. 1-3). Most neurodevelopmental disorders have been difficult to study by GWAS, apart from some progress that has been made in autism4"6. A GWAS was performed on 958 ADHD trios through the International Multicentre ADHD Genetics (IMAGE) study, but no locus reaching genome-wide significance was found7'8. However, a PBAT (see URLs) analysis of the quantitative measures showed nominal significance of SNPs tagging CDH13 (rs6565113) and GFOD1 (rs552655)9. A SNP in linkage disequilibrium affecting CDH13 has previously been reported in two independent ADHD GWAS10. Duplications of 16pl3.11 have also been shown to be associated with ADHD11. We previously reported CNV loci that we observed in the first 335 cases with ADHD that we recruited12. Although in that previous study, no CNV loci met the criteria for significance (P < 5 x 10~(-4)), one family in the study had a GRM5 deletion that affected all three children with ADHD and was inherited from the mother, who also had ADHD.