Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes.
Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes.
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欧洲血统个体的遗传分析确定了517个与肝酶相关的基因座。
DOI：
10.1038/s41467-021-22338-2
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发表时间：
2021-05-10
影响因子：
16.6
通讯作者：
VA Million Veteran Program
中科院分区：
文献类型：
--
作者：
Pazoki R;Vujkovic M;Elliott J;Evangelou E;Gill D;Ghanbari M;van der Most PJ;Pinto RC;Wielscher M;Farlik M;Zuber V;de Knegt RJ;Snieder H;Uitterlinden AG;Lifelines Cohort Study;Lynch JA;Jiang X;Said S;Kaplan DE;Lee KM;Serper M;Carr RM;Tsao PS;Atkinson SR;Dehghan A;Tzoulaki I;Ikram MA;Herzig KH;Järvelin MR;Alizadeh BZ;O'Donnell CJ;Saleheen D;Voight BF;Chang KM;Thursz MR;Elliott P;VA Million Veteran Program
血清肝酶浓度与肝功能障碍、代谢和心血管疾病有关。我们使用437，438名英国生物银行参与者的数据对丙氨酸转氨酶（ALT），碱性磷酸酶（ALP）和γ-谷氨酰转移酶（GGT）的血清水平进行遗传分析。来自百万退伍军人计划、鹿特丹研究和生命线研究的315，572名欧洲血统个体的复制确认了517个肝酶SNP。在两项独立的欧洲血统研究中（Airwave健康监测研究和1966年北方芬兰出生队列研究），使用确定的SNP进行的遗传风险评分分析与肝酶的血清活性密切相关。使用所鉴定的SNP的基因集富集分析突出了参与肝脏发育和功能、脂质代谢、胰岛素抵抗和血管形成。孟德尔随机化分析显示肝酶变异与冠心病和缺血性卒中相关。血清肝酶活性升高的遗传风险评分与身体、躯干和肝脏的脂肪百分比以及体重指数较高相关。我们的研究强调了肝脏调节的分子途径在代谢紊乱和心血管疾病中的作用。肝酶的血浆水平提供了对肝功能和相关疾病的见解。在这里，作者对三种肝酶进行了全基因组关联研究，确定了与其血浆浓度相关的遗传变异以及与代谢和心血管疾病的联系。
Serum concentration of hepatic enzymes are linked to liver dysfunction, metabolic and cardiovascular diseases. We perform genetic analysis on serum levels of alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) using data on 437,438 UK Biobank participants. Replication in 315,572 individuals from European descent from the Million Veteran Program, Rotterdam Study and Lifeline study confirms 517 liver enzyme SNPs. Genetic risk score analysis using the identified SNPs is strongly associated with serum activity of liver enzymes in two independent European descent studies (The Airwave Health Monitoring study and the Northern Finland Birth Cohort 1966). Gene-set enrichment analysis using the identified SNPs highlights involvement in liver development and function, lipid metabolism, insulin resistance, and vascular formation. Mendelian randomization analysis shows association of liver enzyme variants with coronary heart disease and ischemic stroke. Genetic risk score for elevated serum activity of liver enzymes is associated with higher fat percentage of body, trunk, and liver and body mass index. Our study highlights the role of molecular pathways regulated by the liver in metabolic disorders and cardiovascular disease. Plasma levels of liver enzymes provide insights into hepatic function and related diseases. Here, the authors perform a genome-wide association study on three liver enzymes, identifying genetic variants associated with their plasma concentration as well as links to metabolic and cardiovascular diseases.
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影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
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.
DOI：
10.1097/ede.0000000000000559
发表时间：
2017-01
期刊：
Epidemiology (Cambridge, Mass.)
影响因子：
--
作者：
Burgess S;Bowden J;Fall T;Ingelsson E;Thompson SG
通讯作者：
Thompson SG
影响因子：
30.8
作者：
Malik R;Chauhan G;Traylor M;Sargurupremraj M;Okada Y;Mishra A;Rutten-Jacobs L;Giese AK;van der Laan SW;Gretarsdottir S;Anderson CD;Chong M;Adams HHH;Ago T;Almgren P;Amouyel P;Ay H;Bartz TM;Benavente OR;Bevan S;Boncoraglio GB;Brown RD Jr;Butterworth AS;Carrera C;Carty CL;Chasman DI;Chen WM;Cole JW;Correa A;Cotlarciuc I;Cruchaga C;Danesh J;de Bakker PIW;DeStefano AL;den Hoed M;Duan Q;Engelter ST;Falcone GJ;Gottesman RF;Grewal RP;Gudnason V;Gustafsson S;Haessler J;Harris TB;Hassan A;Havulinna AS;Heckbert SR;Holliday EG;Howard G;Hsu FC;Hyacinth HI;Ikram MA;Ingelsson E;Irvin MR;Jian X;Jiménez-Conde J;Johnson JA;Jukema JW;Kanai M;Keene KL;Kissela BM;Kleindorfer DO;Kooperberg C;Kubo M;Lange LA;Langefeld CD;Langenberg C;Launer LJ;Lee JM;Lemmens R;Leys D;Lewis CM;Lin WY;Lindgren AG;Lorentzen E;Magnusson PK;Maguire J;Manichaikul A;McArdle PF;Meschia JF;Mitchell BD;Mosley TH;Nalls MA;Ninomiya T;O'Donnell MJ;Psaty BM;Pulit SL;Rannikmäe K;Reiner AP;Rexrode KM;Rice K;Rich SS;Ridker PM;Rost NS;Rothwell PM;Rotter JI;Rundek T;Sacco RL;Sakaue S;Sale MM;Salomaa V;Sapkota BR;Schmidt R;Schmidt CO;Schminke U;Sharma P;Slowik A;Sudlow CLM;Tanislav C;Tatlisumak T;Taylor KD;Thijs VNS;Thorleifsson G;Thorsteinsdottir U;Tiedt S;Trompet S;Tzourio C;van Duijn CM;Walters M;Wareham NJ;Wassertheil-Smoller S;Wilson JG;Wiggins KL;Yang Q;Yusuf S;AFGen Consortium;Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium;International Genomics of Blood Pressure (iGEN-BP) Consortium;INVENT Consortium;STARNET;Bis JC;Pastinen T;Ruusalepp A;Schadt EE;Koplev S;Björkegren JLM;Codoni V;Civelek M;Smith NL;Trégouët DA;Christophersen IE;Roselli C;Lubitz SA;Ellinor PT;Tai ES;Kooner JS;Kato N;He J;van der Harst P;Elliott P;Chambers JC;Takeuchi F;Johnson AD;BioBank Japan Cooperative Hospital Group;COMPASS Consortium;EPIC-CVD Consortium;EPIC-InterAct Consortium;International Stroke Genetics Consortium (ISGC);METASTROKE Consortium;Neurology Working Group of the CHARGE Consortium;NINDS Stroke Genetics Network (SiGN);UK Young Lacunar DNA Study;MEGASTROKE Consortium;Sanghera DK;Melander O;Jern C;Strbian D;Fernandez-Cadenas I;Longstreth WT Jr;Rolfs A;Hata J;Woo D;Rosand J;Pare G;Hopewell JC;Saleheen D;Stefansson K;Worrall BB;Kittner SJ;Seshadri S;Fornage M;Markus HS;Howson JMM;Kamatani Y;Debette S;Dichgans M
通讯作者：
Dichgans 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