Novel loci for major depression identified by genome-wide association study of Sequenced Treatment Alternatives to Relieve Depression and meta-analysis of three studies

S I Shyn; J Shi; J B Kraft; J B Potash; J A Knowles; M M Weissman; H A Garriock; J S Yokoyama; P J McGrath; E J Peters; W A Scheftner; W Coryell; W B Lawson; D Jancic; P V Gejman; A R Sanders; P Holmans; S L Slager; D F Levinson; S P Hamilton

doi:10.1038/mp.2009.125

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Novel loci for major depression identified by genome-wide association study of Sequenced Treatment Alternatives to Relieve Depression and meta-analysis of three studies

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Novel loci for major depression identified by genome-wide association study of Sequenced Treatment Alternatives to Relieve Depression and meta-analysis of three studies

S I Shyn, J Shi, J B Kraft, J B Potash, J A Knowles, M M Weissman, H A Garriock, J S Yokoyama, P J McGrath, E J Peters, …

Molecular psychiatry, Vol.16(2), pp.202-215

02/2011

DOI: 10.1038/mp.2009.125

PMCID: PMC2888856

PMID: 20038947

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Abstract

We report a genome-wide association study (GWAS) of major depressive disorder (MDD) in 1221 cases from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study and 1636 screened controls. No genome-wide evidence for association was detected. We also carried out a meta-analysis of three European-ancestry MDD GWAS data sets: STAR*D, Genetics of Recurrent Early-onset Depression and the publicly available Genetic Association Information Network-MDD data set. These data sets, totaling 3957 cases and 3428 controls, were genotyped using four different platforms (Affymetrix 6.0, 5.0 and 500 K, and Perlegen). For each of 2.4 million HapMap II single-nucleotide polymorphisms (SNPs), using genotyped data where available and imputed data otherwise, single-SNP association tests were carried out in each sample with correction for ancestry-informative principal components. The strongest evidence for association in the meta-analysis was observed for intronic SNPs in ATP6V1B2 (P=6.78 x 10⁻⁷), SP4 (P=7.68 x 10⁻⁷) and GRM7 (P=1.11 x 10⁻⁶). Additional exploratory analyses were carried out for a narrower phenotype (recurrent MDD with onset before age 31, N=2191 cases), and separately for males and females. Several of the best findings were supported primarily by evidence from narrow cases or from either males or females. On the basis of previous biological evidence, we consider GRM7 a strong MDD candidate gene. Larger samples will be required to determine whether any common SNPs are significantly associated with MDD.

Europe

Vacuolar Proton-Translocating ATPases - genetics

Genome-Wide Association Study

Meta-Analysis as Topic

Oligonucleotide Array Sequence Analysis - methods

Humans

Middle Aged

Gene Expression Profiling - methods

Genotype

Male

Young Adult

Receptors, Metabotropic Glutamate - genetics

Depressive Disorder, Major - genetics

Adolescent

Age of Onset

Polymorphism, Single Nucleotide - genetics

Adult

Female

Aged

Principal Component Analysis

Sp4 Transcription Factor - genetics

Details

Title: Subtitle: Novel loci for major depression identified by genome-wide association study of Sequenced Treatment Alternatives to Relieve Depression and meta-analysis of three studies
Creators: S I Shyn - Department of Psychiatry and Institute for Human Genetics, University of California, San Francisco, CA, USA
J Shi
J B Kraft
J B Potash
J A Knowles
M M Weissman
H A Garriock
J S Yokoyama
P J McGrath
E J Peters
W A Scheftner
W Coryell
W B Lawson
D Jancic
P V Gejman
A R Sanders
P Holmans
S L Slager
D F Levinson
S P Hamilton
Resource Type: Journal article
Publication Details: Molecular psychiatry, Vol.16(2), pp.202-215
DOI: 10.1038/mp.2009.125
PMID: 20038947
PMCID: PMC2888856
NLM abbreviation: Mol Psychiatry
ISSN: 1476-5578
eISSN: 1476-5578
Publisher: England
Grant note: T32 MH19552 / NIMH NIH HHS T32 MH019552 / NIMH NIH HHS R25 MH060482 / NIMH NIH HHS T32 MH019126 / NIMH NIH HHS N01MH90003 / NIMH NIH HHS T32 MH020006 / NIMH NIH HHS U54 RR020278 / NCRR NIH HHS R01 MH072802-04 / NIMH NIH HHS R01 MH072802 / NIMH NIH HHS G0800509 / Medical Research Council T32 MH19126 / NIMH NIH HHS F32 MH082562 / NIMH NIH HHS MH072802 / NIMH NIH HHS
Language: English
Date published: 02/2011
Academic Unit: Psychiatry
Record Identifier: 9984003483302771

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