Genome-wide association study of recurrent early-onset major depressive disorder

J. Shi, J. B. Potash, J. A. Knowles, M. M. Weissman, W. Coryell, W. A. Scheftner, W. B. Lawson, J. R. Depaulo, P. V. Gejman, A. R. Sanders, J. K. Johnson, P. Adams, S. Chaudhury, D. Jancic, O. Evgrafov, A. Zvinyatskovskiy, N. Ertman, M. Gladis, K. Neimanas, M. GoodellN. Hale, N. Ney, R. Verma, D. Mirel, P. Holmans, D. F. Levinson

Research output: Contribution to journalArticlepeer-review

Abstract

A genome-wide association study was carried out in 1020 case subjects with recurrent early-onset major depressive disorder (MDD) (onset before age 31) and 1636 control subjects screened to exclude lifetime MDD. 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. No genome-wide significant evidence for association was observed, assuming that nominal P5 × 10 -8 approximates a 5% genome-wide significance threshold. The strongest evidence for association was observed on chromosome 18q22.1 (rs17077540, P1.83 × 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. Larger samples will be required to confirm the hypothesis of association between MDD (and particularly the recurrent early-onset subtype) and common SNPs.

Original languageEnglish (US)
Pages (from-to)193-201
Number of pages9
JournalMolecular psychiatry
Volume16
Issue number2
DOIs
StatePublished - Feb 2011

Keywords

  • GWAS
  • genetics
  • genotype
  • major depressive disorder
  • neuroscience

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health

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