Meta-analysis of sub-Saharan African studies provides insights into genetic architecture of lipid traits.
Meta-analysis of sub-Saharan African studies provides insights into genetic architecture of lipid traits.
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DOI：
10.1038/s41467-022-30098-w
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发表时间：
2022-05-11
影响因子：
16.6
通讯作者：
Ramsay M
中科院分区：
文献类型：
--
作者：
Choudhury A;Brandenburg JT;Chikowore T;Sengupta D;Boua PR;Crowther NJ;Agongo G;Asiki G;Gómez-Olivé FX;Kisiangani I;Maimela E;Masemola-Maphutha M;Micklesfield LK;Nonterah EA;Norris SA;Sorgho H;Tinto H;Tollman S;Graham SE;Willer CJ;AWI-Gen study;H3Africa Consortium;Hazelhurst S;Ramsay M
在欧洲、亚洲和非洲的研究中，与血脂特征有关的遗传关联已经确定了数百种具有明显差异的变异。基于撒哈拉以南非洲地区人群中的脂类性状的GWA(N = 10,603)，我们报告了在GATB地区的一个新的低密度脂蛋白-C关联(P值=1.56 × 10−8)。与其他四个非洲队列(N = 23,718)的Meta分析为低密度脂蛋白与GATB/FHIP1A区的关联提供了支持证据，并发现了接近FHIT基因的新的甘油三酯关联信号(P值=2.66 × 10−8)。我们的数据使得包括LDLR、PMFBP1和LPA在内的几个众所周知的脂质性状基因座的精细定位成为可能。在两项大型全球研究(GLGC和PAGE)中检测到的信号的可转移性随着非洲复制队列规模的增加而不断提高。多基因风险评分分析显示，随着发现数据集和我们队列之间的遗传距离缩小，对低密度脂蛋白水平的预测准确性提高。新的发现随着非洲数据的加入而得到加强。脂肪性状的遗传关联和多基因得分对非洲人的可转移性很低。在这里，作者进行了一个大型的亚Sarahan非洲脂质GWAs，并发现更大的数据集和更好的发现GWAs的全球代表性有助于弥合这一差距。
Genetic associations for lipid traits have identified hundreds of variants with clear differences across European, Asian and African studies. Based on a sub-Saharan-African GWAS for lipid traits in the population cross-sectional AWI-Gen cohort (N = 10,603) we report a novel LDL-C association in the GATB region (P-value=1.56 × 10−8). Meta-analysis with four other African cohorts (N = 23,718) provides supporting evidence for the LDL-C association with the GATB/FHIP1A region and identifies a novel triglyceride association signal close to the FHIT gene (P-value =2.66 × 10−8). Our data enable fine-mapping of several well-known lipid-trait loci including LDLR, PMFBP1 and LPA. The transferability of signals detected in two large global studies (GLGC and PAGE) consistently improves with an increase in the size of the African replication cohort. Polygenic risk score analysis shows increased predictive accuracy for LDL-C levels with the narrowing of genetic distance between the discovery dataset and our cohort. Novel discovery is enhanced with the inclusion of African data. Genetic associations and polygenic scores for lipid traits have low transferability to African individuals. Here, the authors perform a large sub-Sarahan African lipid GWAS and find that larger datasets and better global representation in discovery GWAS help to bridge this gap.
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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：
64.8
作者：
Graham SE;Clarke SL;Wu KH;Kanoni S;Zajac GJM;Ramdas S;Surakka I;Ntalla I;Vedantam S;Winkler TW;Locke AE;Marouli E;Hwang MY;Han S;Narita A;Choudhury A;Bentley AR;Ekoru K;Verma A;Trivedi B;Martin HC;Hunt KA;Hui Q;Klarin D;Zhu X;Thorleifsson G;Helgadottir A;Gudbjartsson DF;Holm H;Olafsson I;Akiyama M;Sakaue S;Terao C;Kanai M;Zhou W;Brumpton BM;Rasheed H;Ruotsalainen SE;Havulinna AS;Veturi Y;Feng Q;Rosenthal EA;Lingren T;Pacheco JA;Pendergrass SA;Haessler J;Giulianini F;Bradford Y;Miller JE;Campbell A;Lin K;Millwood IY;Hindy G;Rasheed A;Faul JD;Zhao W;Weir DR;Turman C;Huang H;Graff M;Mahajan A;Brown MR;Zhang W;Yu K;Schmidt EM;Pandit A;Gustafsson S;Yin X;Luan J;Zhao JH;Matsuda F;Jang HM;Yoon K;Medina-Gomez C;Pitsillides A;Hottenga JJ;Willemsen G;Wood AR;Ji Y;Gao Z;Haworth S;Mitchell RE;Chai JF;Aadahl M;Yao J;Manichaikul A;Warren HR;Ramirez J;Bork-Jensen J;Kårhus LL;Goel A;Sabater-Lleal M;Noordam R;Sidore C;Fiorillo E;McDaid AF;Marques-Vidal P;Wielscher M;Trompet S;Sattar N;Møllehave LT;Thuesen BH;Munz M;Zeng L;Huang J;Yang B;Poveda A;Kurbasic A;Lamina C;Forer L;Scholz M;Galesloot TE;Bradfield JP;Daw EW;Zmuda JM;Mitchell JS;Fuchsberger C;Christensen H;Brody JA;Feitosa MF;Wojczynski MK;Preuss M;Mangino M;Christofidou P;Verweij N;Benjamins JW;Engmann J;Kember RL;Slieker RC;Lo KS;Zilhao NR;Le P;Kleber ME;Delgado GE;Huo S;Ikeda DD;Iha H;Yang J;Liu J;Leonard HL;Marten J;Schmidt B;Arendt M;Smyth LJ;Cañadas-Garre M;Wang C;Nakatochi M;Wong A;Hutri-Kähönen N;Sim X;Xia R;Huerta-Chagoya A;Fernandez-Lopez JC;Lyssenko V;Ahmed M;Jackson AU;Yousri NA;Irvin MR;Oldmeadow C;Kim HN;Ryu S;Timmers PRHJ;Arbeeva L;Dorajoo R;Lange LA;Chai X;Prasad G;Lorés-Motta L;Pauper M;Long J;Li X;Theusch E;Takeuchi F;Spracklen CN;Loukola A;Bollepalli S;Warner SC;Wang YX;Wei WB;Nutile T;Ruggiero D;Sung YJ;Hung YJ;Chen S;Liu F;Yang J;Kentistou KA;Gorski M;Brumat M;Meidtner K;Bielak LF;Smith JA;Hebbar P;Farmaki AE;Hofer E;Lin M;Xue C;Zhang J;Concas MP;Vaccargiu S;van der Most PJ;Pitkänen N;Cade BE;Lee J;van der Laan SW;Chitrala KN;Weiss S;Zimmermann ME;Lee JY;Choi HS;Nethander M;Freitag-Wolf S;Southam L;Rayner NW;Wang CA;Lin SY;Wang JS;Couture C;Lyytikäinen LP;Nikus K;Cuellar-Partida G;Vestergaard H;Hildalgo B;Giannakopoulou O;Cai Q;Obura MO;van Setten J;Li X;Schwander K;Terzikhan N;Shin JH;Jackson RD;Reiner AP;Martin LW;Chen Z;Li L;Highland HM;Young KL;Kawaguchi T;Thiery J;Bis JC;Nadkarni GN;Launer LJ;Li H;Nalls MA;Raitakari OT;Ichihara S;Wild SH;Nelson CP;Campbell H;Jäger S;Nabika T;Al-Mulla F;Niinikoski H;Braund PS;Kolcic I;Kovacs P;Giardoglou T;Katsuya T;Bhatti KF;de Kleijn D;de Borst GJ;Kim EK;Adams HHH;Ikram MA;Zhu X;Asselbergs FW;Kraaijeveld AO;Beulens JWJ;Shu XO;Rallidis LS;Pedersen O;Hansen T;Mitchell P;Hewitt AW;Kähönen M;Pérusse L;Bouchard C;Tönjes A;Chen YI;Pennell CE;Mori TA;Lieb W;Franke A;Ohlsson C;Mellström D;Cho YS;Lee H;Yuan JM;Koh WP;Rhee SY;Woo JT;Heid IM;Stark KJ;Völzke H;Homuth G;Evans MK;Zonderman AB;Polasek O;Pasterkamp G;Hoefer IE;Redline S;Pahkala K;Oldehinkel AJ;Snieder H;Biino G;Schmidt R;Schmidt H;Chen YE;Bandinelli S;Dedoussis G;Thanaraj TA;Kardia SLR;Kato N;Schulze MB;Girotto G;Jung B;Böger CA;Joshi PK;Bennett DA;De Jager PL;Lu X;Mamakou V;Brown M;Caulfield MJ;Munroe PB;Guo X;Ciullo M;Jonas JB;Samani NJ;Kaprio J;Pajukanta P;Adair LS;Bechayda SA;de Silva HJ;Wickremasinghe AR;Krauss RM;Wu JY;Zheng W;den Hollander AI;Bharadwaj D;Correa A;Wilson JG;Lind L;Heng CK;Nelson AE;Golightly YM;Wilson JF;Penninx B;Kim HL;Attia J;Scott RJ;Rao DC;Arnett DK;Hunt SC;Walker M;Koistinen HA;Chandak GR;Yajnik CS;Mercader JM;Tusié-Luna T;Aguilar-Salinas CA;Villalpando CG;Orozco L;Fornage M;Tai ES;van Dam RM;Lehtimäki T;Chaturvedi N;Yokota M;Liu J;Reilly DF;McKnight AJ;Kee F;Jöckel KH;McCarthy MI;Palmer CNA;Vitart V;Hayward C;Simonsick E;van Duijn CM;Lu F;Qu J;Hishigaki H;Lin X;März W;Parra EJ;Cruz M;Gudnason V;Tardif JC;Lettre G;'t Hart LM;Elders PJM;Damrauer SM;Kumari M;Kivimaki M;van der Harst P;Spector TD;Loos RJF;Province MA;Psaty BM;Brandslund I;Pramstaller PP;Christensen K;Ripatti S;Widén E;Hakonarson H;Grant SFA;Kiemeney LALM;de Graaf J;Loeffler M;Kronenberg F;Gu D;Erdmann J;Schunkert H;Franks PW;Linneberg A;Jukema JW;Khera AV;Männikkö M;Jarvelin MR;Kutalik Z;Cucca F;Mook-Kanamori DO;van Dijk KW;Watkins H;Strachan DP;Grarup N;Sever P;Poulter N;Rotter JI;Dantoft TM;Karpe F;Neville MJ;Timpson NJ;Cheng CY;Wong TY;Khor CC;Sabanayagam C;Peters A;Gieger C;Hattersley AT;Pedersen NL;Magnusson PKE;Boomsma DI;de Geus EJC;Cupples LA;van Meurs JBJ;Ghanbari M;Gordon-Larsen P;Huang W;Kim YJ;Tabara Y;Wareham NJ;Langenberg C;Zeggini E;Kuusisto J;Laakso M;Ingelsson E;Abecasis G;Chambers JC;Kooner JS;de Vries PS;Morrison AC;North KE;Daviglus M;Kraft P;Martin NG;Whitfield JB;Abbas S;Saleheen D;Walters RG;Holmes MV;Black C;Smith BH;Justice AE;Baras A;Buring JE;Ridker PM;Chasman DI;Kooperberg C;Wei WQ;Jarvik GP;Namjou B;Hayes MG;Ritchie MD;Jousilahti P;Salomaa V;Hveem K;Åsvold BO;Kubo M;Kamatani Y;Okada Y;Murakami Y;Thorsteinsdottir U;Stefansson K;Ho YL;Lynch JA;Rader DJ;Tsao PS;Chang KM;Cho K;O'Donnell CJ;Gaziano JM;Wilson P;Rotimi CN;Hazelhurst S;Ramsay M;Trembath RC;van Heel DA;Tamiya G;Yamamoto M;Kim BJ;Mohlke KL;Frayling TM;Hirschhorn JN;Kathiresan S;VA Million Veteran Program;Global Lipids Genetics Consortium*;Boehnke M;Natarajan P;Peloso GM;Brown CD;Morris AP;Assimes TL;Deloukas P;Sun YV;Willer CJ
通讯作者：
Willer CJ
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
影响因子：
14.9
作者：
Buniello, Annalisa;MacArthur, Jacqueline A. L.;Parkinson, Helen
通讯作者：
Parkinson, Helen
影响因子：
16.6
作者：
Duncan, L.;Shen, H.;Domingue, B.
通讯作者：
Domingue, B.