Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression.
Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression.
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DOI：
10.1038/s41588-018-0090-3
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发表时间：
2018-05
期刊：
影响因子：
30.8
通讯作者：
Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
中科院分区：
文献类型：
--
作者：
Wray NR;Ripke S;Mattheisen M;Trzaskowski M;Byrne EM;Abdellaoui A;Adams MJ;Agerbo E;Air TM;Andlauer TMF;Bacanu SA;Bækvad-Hansen M;Beekman AFT;Bigdeli TB;Binder EB;Blackwood DRH;Bryois J;Buttenschøn HN;Bybjerg-Grauholm J;Cai N;Castelao E;Christensen JH;Clarke TK;Coleman JIR;Colodro-Conde L;Couvy-Duchesne B;Craddock N;Crawford GE;Crowley CA;Dashti HS;Davies G;Deary IJ;Degenhardt F;Derks EM;Direk N;Dolan CV;Dunn EC;Eley TC;Eriksson N;Escott-Price V;Kiadeh FHF;Finucane HK;Forstner AJ;Frank J;Gaspar HA;Gill M;Giusti-Rodríguez P;Goes FS;Gordon SD;Grove J;Hall LS;Hannon E;Hansen CS;Hansen TF;Herms S;Hickie IB;Hoffmann P;Homuth G;Horn C;Hottenga JJ;Hougaard DM;Hu M;Hyde CL;Ising M;Jansen R;Jin F;Jorgenson E;Knowles JA;Kohane IS;Kraft J;Kretzschmar WW;Krogh J;Kutalik Z;Lane JM;Li Y;Li Y;Lind PA;Liu X;Lu L;MacIntyre DJ;MacKinnon DF;Maier RM;Maier W;Marchini J;Mbarek H;McGrath P;McGuffin P;Medland SE;Mehta D;Middeldorp CM;Mihailov E;Milaneschi Y;Milani L;Mill J;Mondimore FM;Montgomery GW;Mostafavi S;Mullins N;Nauck M;Ng B;Nivard MG;Nyholt DR;O'Reilly PF;Oskarsson H;Owen MJ;Painter JN;Pedersen CB;Pedersen MG;Peterson RE;Pettersson E;Peyrot WJ;Pistis G;Posthuma D;Purcell SM;Quiroz JA;Qvist P;Rice JP;Riley BP;Rivera M;Saeed Mirza S;Saxena R;Schoevers R;Schulte EC;Shen L;Shi J;Shyn SI;Sigurdsson E;Sinnamon GBC;Smit JH;Smith DJ;Stefansson H;Steinberg S;Stockmeier CA;Streit F;Strohmaier J;Tansey KE;Teismann H;Teumer A;Thompson W;Thomson PA;Thorgeirsson TE;Tian C;Traylor M;Treutlein J;Trubetskoy V;Uitterlinden AG;Umbricht D;Van der Auwera S;van Hemert AM;Viktorin A;Visscher PM;Wang Y;Webb BT;Weinsheimer SM;Wellmann J;Willemsen G;Witt SH;Wu Y;Xi HS;Yang J;Zhang F;eQTLGen;23andMe;Arolt V;Baune BT;Berger K;Boomsma DI;Cichon S;Dannlowski U;de Geus ECJ;DePaulo JR;Domenici E;Domschke K;Esko T;Grabe HJ;Hamilton SP;Hayward C;Heath AC;Hinds DA;Kendler KS;Kloiber S;Lewis G;Li QS;Lucae S;Madden PFA;Magnusson PK;Martin NG;McIntosh AM;Metspalu A;Mors O;Mortensen PB;Müller-Myhsok B;Nordentoft M;Nöthen MM;O'Donovan MC;Paciga SA;Pedersen NL;Penninx BWJH;Perlis RH;Porteous DJ;Potash JB;Preisig M;Rietschel M;Schaefer C;Schulze TG;Smoller JW;Stefansson K;Tiemeier H;Uher R;Völzke H;Weissman MM;Werge T;Winslow AR;Lewis CM;Levinson DF;Breen G;Børglum AD;Sullivan PF;Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
重性抑郁症（MDD）是一种常见的疾病，伴随着相当大的发病率，死亡率，成本和自杀的风险增加。我们对135，458例病例和344，901例对照进行了全基因组关联（GWA）荟萃分析，我们确定了44个独立和显著的基因座。遗传学发现与重性抑郁症的临床特征有关，并涉及在病例中表现出解剖学差异的大脑区域。抗抑郁药物的靶点和参与基因剪接的基因富集了较小的关联信号。我们发现抑郁症的遗传风险与教育程度、体重和精神分裂症有重要关系：较低的教育程度和较高的体重是单纯的因果关系，而抑郁症和精神分裂症反映了部分共同的生物学病因。所有人都携带或多或少的重度抑郁症遗传风险因素。这些发现有助于提炼和定义重性抑郁症的基础，并暗示临床表型的风险持续测量。
Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association (GWA) meta-analysis based in 135,458 cases and 344,901 control, We identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression, and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal. We found important relations of genetic risk for major depression with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were putatively causal whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry lesser or greater numbers of genetic risk factors for major depression. These findings help refine and define the basis of major depression and imply a continuous measure of risk underlies the clinical phenotype.