Original Article

Molecular Psychiatry (2011) 16, 202–215; doi:10.1038/mp.2009.125; published online 29 December 2009

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 Shyn1,12, J Shi2,12, J B Kraft1, J B Potash3, J A Knowles4, M M Weissman5, H A Garriock1, J S Yokoyama1, P J McGrath5, E J Peters1, W A Scheftner6, W Coryell7, W B Lawson8, D Jancic3, P V Gejman9, A R Sanders9, P Holmans10, S L Slager11, D F Levinson2 and S P Hamilton1

  1. 1Department of Psychiatry and Institute for Human Genetics, University of California, San Francisco, CA, USA
  2. 2Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, CA, USA
  3. 3Department of Psychiatry, Johns Hopkins University, Baltimore, MD, USA
  4. 4Department of Psychiatry, University of Southern California, Los Angeles, CA, USA
  5. 5Department of Psychiatry, Columbia University College of Physicians and Surgeons and New York State Psychiatric Institute, New York, NY, USA
  6. 6Department of Psychiatry, Rush University Hospital, Chicago, IL, USA
  7. 7Department of Psychiatry, University of Iowa, Iowa City, IA, USA
  8. 8Department of Psychiatry, Howard University, Washington, DC, USA
  9. 9NorthShore University HealthCare, Evanston, IL, USA
  10. 10Department of Psychological Medicine, Cardiff University, Cardiff, UK
  11. 11Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA

Correspondence: Dr S Hamilton, Department of Psychiatry, UCSF, 401 Parnassus Ave., Box 0984-NGL, Rm.G-70, San Francisco, CA 94143-0984, USA. E-mail: SteveH@lppi.ucsf.edu; Dr D Levinson, Department of Psychiatry, Stanford University, 701 Welch Rd., Suite A-3325, Palo Alto, CA 94304, USA. E-mail: dflev@stanford.edu

12These two authors contributed equally to this work.

Received 23 March 2009; Revised 20 August 2009; Accepted 27 August 2009; Published online 29 December 2009.

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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 500K, 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 × 10−7), SP4 (P=7.68 × 10−7) and GRM7 (P=1.11 × 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.

Keywords:

major depressive disorder; genetics; GWAS; meta-analysis; neuroscience