|Citation||Shi, 2011 PubMed
|Full Info||Shi, J., Potash, J.B., Knowles, J.A., Weissman, M.M., Coryell, W., Scheftner, W.A., Lawson, W.B., DePaulo, J.R., Jr., Gejman, P.V., Sanders, A.R. et al. (2011) Genome-wide association study of recurrent early-onset major depressive disorder. Mol Psychiatry, 16, 193-201.
|Hypothesis or Background
|Sample Information||1020 case subjects with recurrent early-onset major depressive disorder (MDD) (onset before age 31) and 1636 control subjects screened to exclude lifetime MDD|
|Method Detail||Subjects were genotyped with the Affymetrix 6.0 platform. After extensive quality control procedures, 671 424 autosomal single nucleotide polymorphisms (SNPs) and 25 068 X chromosome SNPs with minor allele frequency greater than 1% were available for analysis. An additional 1 892 186 HapMap II SNPs were analyzed based on imputed genotypic data. Single-SNP logistic regression trend tests were computed, with correction for ancestry-informative principal component scores.
|Result||No genome-wide significant evidence for association was observed, assuming that nominal P<5 x 10(-8) approximates a 5% genome-wide significance threshold. The strongest evidence for association was observed on chromosome 18q22.1 (rs17077540, P=1.83 x 10(-7)) in a region that has produced some evidence for linkage to bipolar-I or -II disorder in several studies, within an mRNA detected in human brain tissue (BC053410) and approximately 75 kb upstream of DSEL. Comparing these results with those of a meta-analysis of three MDD GWAS data sets reported in a companion article, we note that among the strongest signals observed in the GenRED sample, the meta-analysis provided the greatest support (although not at a genome-wide significant level) for association of MDD to SNPs within SP4, a brain-specific transcription factor
|Conclusions||Larger samples will be required to confirm the hypothesis of association between MDD (and particularly the recurrent early-onset subtype) and common SNPs.
Relationships reported by Shi, 2011