@article{1a17eb20480a4ae5ab0d4e1661832ab1,
title = "Novel loci for major depression identified by genome-wide association study of Sequenced Treatment Alternatives to Relieve Depression and meta-analysis of three studies",
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 (P6.78 × 10-7), SP4 (P7.68 × 10-7) and GRM7 (P1.11 × 10-6). Additional exploratory analyses were carried out for a narrower phenotype (recurrent MDD with onset before age 31, N2191 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 = "GWAS, genetics, major depressive disorder, meta-analysis, neuroscience",
author = "Shyn, {S. I.} and J. Shi and Kraft, {J. B.} and Potash, {J. B.} and Knowles, {J. A.} and Weissman, {M. M.} and Garriock, {H. A.} and Yokoyama, {J. S.} and McGrath, {P. J.} and Peters, {E. J.} and Scheftner, {W. A.} and W. Coryell and Lawson, {W. B.} and D. Jancic and Gejman, {P. V.} and Sanders, {A. R.} and P. Holmans and Slager, {S. L.} and Levinson, {D. F.} and Hamilton, {S. P.}",
note = "Funding Information: The STAR*D GWAS study acknowledges Shaun Purcell (Broad Institute) for technical assistance and Eric Jorgenson (UCSF) for helpful discussion. Geno-typing of STAR*D was supported by an NIMH grant to SPH (MH072802), and made possible by the laboratory of Pui Kwok (UCSF) and the UCSF Institute for Human Genetics. This work was further supported by NIMH training funds to SIS (R25 MH060482 & T32 MH19126) and to HAG (F32 MH082562 & T32 MH19552); a NARSAD Young Investigators Award to HAG (A109584); the State of New York, which provided partial support to PJM for this work. The authors appreciate the efforts of the STAR*D Investigator Team for acquiring, compiling and sharing the STAR*D clinical data set. STAR*D was funded by the National Institute of Mental Health through a contract (N01MH90003) to the University of Texas South-western Medical Center at Dallas (A John Rush, principal investigator). The authors thank Stephen Wisniewski, PhD, Director, STAR*D Data Coordinating Center, University of Pittsburgh, for demographic data. The GenRED project is supported by grants from NIMH (see online Supplementary Acknowledgements). We acknowledge the contributions of Dr George S Zubenko and Dr Wendy N Zubenko, Department of Psychiatry, University of Pittsburgh School of Medicine, to the GenRED I project. The NIMH Cell Repository at Rutgers University and the NIMH Center for Collaborative Genetic Studies on Mental Disorders made essential contributions to this project. Genotyping was carried out by the Broad Institute Center for Genotyping and Analysis with support from grant U54 RR020278 (which partially subsidized the genotyping of the GenRED cases) from the National Center for Research Resources. The meta-analysis was supported by grants from NIMH and the National Cancer Institute, and by support from the State of New York. GWAS data for the GAIN– MDD data set were accessed by DFL through the Genetic Association Information Network (GAIN), through dbGaP accession number phs000020.v1.p1 (http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/ study.cgi?study_id = phs000020.v2.p1); samples and associated phenotype data for Major Depression: Stage 1 Genome-wide Association in Population-Based Samples were provided by P Sullivan. Data for Molecular Genetics of Schizophrenia (MGS) control subjects was used here by permission of the MGS project. Collection and quality control analyses of the control data set were supported by grants from NIMH and the National Alliance for Research on Schizophrenia and Depression. Genotyping of the controls was supported by grants from NIMH and by the Genetic Association Information Network (GAIN) (http://www.fnih.org/index.php?option = com_content &task = view&id = 338&Itemid = 454). Control data are available through dbGAP (http://www.ncbi.nlm.nih. gov/gap). We are grateful to Knowledge Networks, Inc. (Menlo Park, CA, USA) for assistance in collecting the control data set. The authors express their profound appreciation to the individuals who participated in this project, and to the many clinicians who facilitated the referral of participants to the study.",
year = "2011",
month = feb,
doi = "10.1038/mp.2009.125",
language = "English (US)",
volume = "16",
pages = "202--215",
journal = "Molecular psychiatry",
issn = "1359-4184",
publisher = "Nature Publishing Group",
number = "2",
}