Novel loci for major depression identified by genome-wide association study of Sequenced Treatment Alternatives to Relieve Depression and meta-analysis of three studies.
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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DOI：
10.1038/mp.2009.125
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发表时间：
2011-02
影响因子：
11
通讯作者：
中科院分区：
文献类型：
--
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我们报告了一项重性抑郁障碍（MDD）的全基因组关联研究（GWAS），研究对象为来自缓解抑郁症序贯治疗替代方案（星星 *D）研究的1,221例患者和1,636例筛选对照。没有检测到全基因组关联的证据。我们还对三个欧洲血统MDD GWAS数据集进行了荟萃分析：星星 *D，复发性早发性抑郁症遗传学（GenRED）和公开可用的遗传关联信息网络MDD数据集（GAIN-MDD）。这些数据集，共计3，957例病例和3，428例对照，使用四种不同的平台（Affytron 6.0，5.0和500 K以及Perlegen）进行基因分型。对于240万个HapMap II SNP中的每一个，使用可用的基因型数据和插补数据，在每个样本中进行单SNP关联检验，并校正祖先信息主成分。在荟萃分析中，观察到ATP 6V 1B 2（P = 6.78 × 10−7），SP 4（P = 7.68 × 10 −7）和GRM 7（P = 1.11 × 10−6）中内含子SNP的关联性最强。对较窄的表型（31岁之前发作的复发性MDD，N = 2，191例病例）进行了额外的探索性分析，并分别对男性和女性进行了分析。一些最好的发现主要是由来自狭义病例或男性或女性的证据支持的。基于先前的生物学证据，我们认为GRM 7是一个强有力的MDD候选基因。需要更大的样本来确定是否有任何常见的SNP与MDD显著相关。
We report a genome-wide association study (GWAS) of major depressive disorder (MDD) in 1,221 cases from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study and 1,636 screened controls. No genome-wide evidence for association was detected. We also carried out a meta-analysis of three European-ancestry MDD GWAS datasets: STAR*D, Genetics of Recurrent Early-Onset Depression (GenRED) and the publicly-available Genetic Association Information Network MDD dataset (GAIN-MDD). These datasets, totaling 3,957 cases and 3,428 controls, were genotyped using four different platforms (Affymetrix 6.0, 5.0 and 500K, and Perlegen). For each of 2.4 million HapMap II 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 = 2,191 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. Based on 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.
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影响因子：
30.8
作者：
Marchini, Jonathan;Howie, Bryan;Donnelly, Peter
通讯作者：
Donnelly, Peter
影响因子：
6.9
作者：
Kendler, KS;Gardner, CO;Prescott, CA
通讯作者：
Prescott, CA
影响因子：
4.7
作者：
Mao, Xianrong;Yang, Shao-Hua;Barger, Steven W.
通讯作者：
Barger, Steven W.
影响因子：
30.8
作者：
Kathiresan S;Willer CJ;Peloso GM;Demissie S;Musunuru K;Schadt EE;Kaplan L;Bennett D;Li Y;Tanaka T;Voight BF;Bonnycastle LL;Jackson AU;Crawford G;Surti A;Guiducci C;Burtt NP;Parish S;Clarke R;Zelenika D;Kubalanza KA;Morken MA;Scott LJ;Stringham HM;Galan P;Swift AJ;Kuusisto J;Bergman RN;Sundvall J;Laakso M;Ferrucci L;Scheet P;Sanna S;Uda M;Yang Q;Lunetta KL;Dupuis J;de Bakker PI;O'Donnell CJ;Chambers JC;Kooner JS;Hercberg S;Meneton P;Lakatta EG;Scuteri A;Schlessinger D;Tuomilehto J;Collins FS;Groop L;Altshuler D;Collins R;Lathrop GM;Melander O;Salomaa V;Peltonen L;Orho-Melander M;Ordovas JM;Boehnke M;Abecasis GR;Mohlke KL;Cupples LA
通讯作者：
Cupples LA
影响因子：
30.8
作者：
Ferreira, Manuel A. R.;O'Donovan, Michael C.;Meng, Yan A.;Jones, Ian R.;Ruderfer, Douglas M.;Jones, Lisa;Fan, Jinbo;Kirov, George;Perlis, Roy H.;Green, Elaine K.;Smoller, Jordan W.;Grozeva, Detelina;Stone, Jennifer;Nikolov, Ivan;Chambert, Kimberly;Hamshere, Marian L.;Nimgaonkar, Vishwajit L.;Moskvina, Valentina;Thase, Michael E.;Caesar, Sian;Sachs, Gary S.;Franklin, Jennifer;Gordon-Smith, Katherine;Ardlie, Kristin G.;Gabriel, Stacey B.;Fraser, Christine;Blumenstiel, Brendan;Defelice, Matthew;Breen, Gerome;Gill, Michael;Morris, Derek W.;Elkin, Amanda;Muir, Walter J.;McGhee, Kevin A.;Williamson, Richard;MacIntyre, Donald J.;MacLean, Alan W.;Clair, David St;Robinson, Michelle;Van Beck, Margaret;Pereira, Ana C. P.;Kandaswamy, Radhika;McQuillin, Andrew;Collier, David A.;Bass, Nicholas J.;Young, Allan H.;Lawrence, Jacob;Ferrier, I. Nicol;Anjorin, Adebayo;Farmer, Anne;Curtis, David;Scolnick, Edward M.;McGuffin, Peter;Daly, Mark J.;Corvin, Aiden P.;Holmans, Peter A.;Blackwood, Douglas H.;Gurling, Hugh M.;Owen, Michael J.;Purcell, Shaun M.;Sklar, Pamela;Craddock, Nick
通讯作者：
Craddock, Nick