Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors.
Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors.
复制标题
DOI：
10.1016/j.biopsych.2021.05.029
复制
发表时间：
2022-02-01
影响因子：
10.6
通讯作者：
Ruderfer DM
中科院分区：
文献类型：
--
作者：
Mullins N;Kang J;Campos AI;Coleman JRI;Edwards AC;Galfalvy H;Levey DF;Lori A;Shabalin A;Starnawska A;Su MH;Watson HJ;Adams M;Awasthi S;Gandal M;Hafferty JD;Hishimoto A;Kim M;Okazaki S;Otsuka I;Ripke S;Ware EB;Bergen AW;Berrettini WH;Bohus M;Brandt H;Chang X;Chen WJ;Chen HC;Crawford S;Crow S;DiBlasi E;Duriez P;Fernández-Aranda F;Fichter MM;Gallinger S;Glatt SJ;Gorwood P;Guo Y;Hakonarson H;Halmi KA;Hwu HG;Jain S;Jamain S;Jiménez-Murcia S;Johnson C;Kaplan AS;Kaye WH;Keel PK;Kennedy JL;Klump KL;Li D;Liao SC;Lieb K;Lilenfeld L;Liu CM;Magistretti PJ;Marshall CR;Mitchell JE;Monson ET;Myers RM;Pinto D;Powers A;Ramoz N;Roepke S;Rozanov V;Scherer SW;Schmahl C;Sokolowski M;Strober M;Thornton LM;Treasure J;Tsuang MT;Witt SH;Woodside DB;Yilmaz Z;Zillich L;Adolfsson R;Agartz I;Air TM;Alda M;Alfredsson L;Andreassen OA;Anjorin A;Appadurai V;Soler Artigas M;Van der Auwera S;Azevedo MH;Bass N;Bau CHD;Baune BT;Bellivier F;Berger K;Biernacka JM;Bigdeli TB;Binder EB;Boehnke M;Boks MP;Bosch R;Braff DL;Bryant R;Budde M;Byrne EM;Cahn W;Casas M;Castelao E;Cervilla JA;Chaumette B;Cichon S;Corvin A;Craddock N;Craig D;Degenhardt F;Djurovic S;Edenberg HJ;Fanous AH;Foo JC;Forstner AJ;Frye M;Fullerton JM;Gatt JM;Gejman PV;Giegling I;Grabe HJ;Green MJ;Grevet EH;Grigoroiu-Serbanescu M;Gutierrez B;Guzman-Parra J;Hamilton SP;Hamshere ML;Hartmann A;Hauser J;Heilmann-Heimbach S;Hoffmann P;Ising M;Jones I;Jones LA;Jonsson L;Kahn RS;Kelsoe JR;Kendler KS;Kloiber S;Koenen KC;Kogevinas M;Konte B;Krebs MO;Landén M;Lawrence J;Leboyer M;Lee PH;Levinson DF;Liao C;Lissowska J;Lucae S;Mayoral F;McElroy SL;McGrath P;McGuffin P;McQuillin A;Medland SE;Mehta D;Melle I;Milaneschi Y;Mitchell PB;Molina E;Morken G;Mortensen PB;Müller-Myhsok B;Nievergelt C;Nimgaonkar V;Nöthen MM;O'Donovan MC;Ophoff RA;Owen MJ;Pato C;Pato MT;Penninx BWJH;Pimm J;Pistis G;Potash JB;Power RA;Preisig M;Quested D;Ramos-Quiroga JA;Reif A;Ribasés M;Richarte V;Rietschel M;Rivera M;Roberts A;Roberts G;Rouleau GA;Rovaris DL;Rujescu D;Sánchez-Mora C;Sanders AR;Schofield PR;Schulze TG;Scott LJ;Serretti A;Shi J;Shyn SI;Sirignano L;Sklar P;Smeland OB;Smoller JW;Sonuga-Barke EJS;Spalletta G;Strauss JS;Świątkowska B;Trzaskowski M;Turecki G;Vilar-Ribó L;Vincent JB;Völzke H;Walters JTR;Shannon Weickert C;Weickert TW;Weissman MM;Williams LM;Wray NR;Zai CC;Ashley-Koch AE;Beckham JC;Hauser ER;Hauser MA;Kimbrel NA;Lindquist JH;McMahon B;Oslin DW;Qin X;Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium;Bipolar Disorder Working Group of the Psychiatric Genomics Consortium;Eating Disorders Working Group of the Psychiatric Genomics Consortium;German Borderline Genomics Consortium;MVP Suicide Exemplar Workgroup;VA Million Veteran Program;Agerbo E;Børglum AD;Breen G;Erlangsen A;Esko T;Gelernter J;Hougaard DM;Kessler RC;Kranzler HR;Li QS;Martin NG;McIntosh AM;Mors O;Nordentoft M;Olsen CM;Porteous D;Ursano RJ;Wasserman D;Werge T;Whiteman DC;Bulik CM;Coon H;Demontis D;Docherty AR;Kuo PH;Lewis CM;Mann JJ;Rentería ME;Smith DJ;Stahl EA;Stein MB;Streit F;Willour V;Ruderfer DM
自杀是世界范围内的主要死因，非致命性自杀企图发生得更为频繁，是残疾和社会经济负担的主要来源。两者都有实质性的遗传病因，这与相关精神疾病的病因部分相同，部分不同。我们在国际自杀遗传学联盟（ISGC）中对29，782例自杀未遂（SA）病例和519，961例对照进行了全基因组关联研究（GWAS）。SA的GWAS以精神疾病为条件，通过基于多性状的条件分析和联合分析，使用GWAS汇总统计量，以消除精神疾病介导的SA的遗传效应。我们调查了SA、精神疾病和其他已知风险因素的共享和不同遗传结构。两个位点达到SA的全基因组意义：主要组织相容性复合体和7号染色体上的一个基因间位点，后者在精神疾病调理后仍与SA相关，并在百万退伍军人计划的一个独立队列中复制。这个位点与冒险行为、吸烟和失眠有关。SA与精神疾病，特别是重性抑郁症，以及吸烟，疼痛，冒险行为，睡眠障碍，教育程度低，生殖特征，社会经济地位低和一般健康状况较差具有很强的遗传相关性。在对精神疾病进行调节后，SA和精神疾病之间的遗传相关性降低，而那些具有非精神病特征的人基本保持不变。我们的研究结果确定了一个风险位点，有助于更强烈的SA比其他表型，并建议SA和已知的风险因素，不介导的精神疾病之间的共享的潜在生物学。
Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
登录
查看更多内容
遗传对人体组织基因表达的影响。
影响因子：
64.8
作者：
GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Lead analysts:;Laboratory, Data Analysis &Coordinating Center (LDACC):;NIH program management:;Biospecimen collection:;Pathology:;eQTL manuscript working group:;Battle A;Brown CD;Engelhardt BE;Montgomery SB
通讯作者：
Montgomery SB
DOI：
10.1176/appi.ajp.2020.19101025
发表时间：
2020-10-01
期刊：
The American journal of psychiatry
影响因子：
--
作者：
Docherty AR;Shabalin AA;DiBlasi E;Monson E;Mullins N;Adkins DE;Bacanu SA;Bakian AV;Crowell S;Chen D;Darlington TM;Callor WB;Christensen ED;Gray D;Keeshin B;Klein M;Anderson JS;Jerominski L;Hayward C;Porteous DJ;McIntosh A;Li Q;Coon H
通讯作者：
Coon H
影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
DOI：
10.1002/ajmg.b.32709
发表时间：
2019-09-01
影响因子：
2.8
作者：
Hubel, Christopher;Gaspar, Helena A.;Breen, Gerome
通讯作者：
Breen, Gerome