AFA: Ancestry-specific allele frequency estimation in admixed populations: The Hispanic Community Health Study/Study of Latinos.
AFA: Ancestry-specific allele frequency estimation in admixed populations: The Hispanic Community Health Study/Study of Latinos.
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DOI：
10.1016/j.xhgg.2022.100096
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发表时间：
2022-04-14
期刊：
影响因子：
--
通讯作者：
Sofer T
中科院分区：
文献类型：
--
作者：
Granot-Hershkovitz E;Sun Q;Argos M;Zhou H;Lin X;Browning SR;Sofer T
混合人群中等位基因频率的估计，如西班牙裔和拉丁裔，依赖于样本的特定混合物组成，因此可能会在两个看似相似的人群之间存在差异。然而，祖先特异性等位基因频率，即，与混合群体的祖先群体有关的基因组序列，可能特别适用于对遗传变异进行优先排序，以用于遗传发现和个性化基因组健康。我们开发了一种混合群体中祖先特异性等位基因频率估计（AFA）方法，用于估计具有无限祖先的混合群体中双等位基因变异的频率。AFA使用最大似然估计，通过对具有给定遗传祖先比例的等位基因的条件概率进行建模。它可以使用包含变体的局部祖先间隔比例（混合人群中局部祖先特异性等位基因频率估计[LAFA]）或遗传祖先的全局比例（混合人群中全局祖先特异性等位基因频率估计[GAFA]），这更容易计算并且更广泛可用。仿真和与现有软件的比较证明了该方法的高精度。我们对来自西班牙裔社区健康研究/拉丁美洲人研究（HCHS/SOL）的19，000名西班牙裔和拉丁美洲人的高质量估算数据实施了AFA，这是一个未充分研究的混合人群，具有三个主要的大陆血统：美洲印第安人，欧洲人和非洲人。将欧洲和非洲的估计频率与各自的gnomAD频率进行比较，显示出高度相关性（Pearson R2 = 0.97-0.99）。我们提供了一个全基因组数据集的估计祖先特异性等位基因频率的可用变体与等位基因频率在5%和95%之间的至少一个三个祖先的人口。美洲印第安人丰富的变异与心脏代谢性状的关联分析确定了5个与拉美裔和西班牙裔的脂质性状相关的基因座，证明了混合人群中祖先特异性等位基因频率的实用性。我们开发了一种方法，祖先特异性等位基因频率估计在混合人群（AFA），估计频率的双等位基因变异的混合人群与无限数量的祖先，使用本地或全球比例的祖先。遗传学特异性等位基因频率有助于混合人群的研究和个性化健康。
Allele frequency estimates in admixed populations, such as Hispanics and Latinos, rely on the sample’s specific admixture composition and thus may differ between two seemingly similar populations. However, ancestry-specific allele frequencies, i.e., pertaining to the ancestral populations of an admixed group, may be particularly useful for prioritizing genetic variants for genetic discovery and personalized genomic health. We developed a method, ancestry-specific allele frequency estimation in admixed populations (AFA), to estimate the frequencies of biallelic variants in admixed populations with an unlimited number of ancestries. AFA uses maximum-likelihood estimation by modeling the conditional probability of having an allele given proportions of genetic ancestries. It can be applied using either local ancestry interval proportions encompassing the variant (local-ancestry-specific allele frequency estimations in admixed populations [LAFAs]) or global proportions of genetic ancestries (global-ancestry-specific allele frequency estimations in admixed populations [GAFAs]), which are easier to compute and are more widely available. Simulations and comparisons to existing software demonstrated the high accuracy of the method. We implemented AFA on high-quality imputed data of ∼9,000 Hispanics and Latinos from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), an understudied, admixed population with three predominant continental ancestries: Amerindian, European, and African. Comparison of the European and African estimated frequencies to the respective gnomAD frequencies demonstrated high correlations (Pearson R2 = 0.97–0.99). We provide a genome-wide dataset of the estimated ancestry-specific allele frequencies for available variants with allele frequency between 5% and 95% in at least one of the three ancestral populations. Association analysis of Amerindian-enriched variants with cardiometabolic traits identified five loci associated with lipid traits in Hispanics and Latinos, demonstrating the utility of ancestry-specific allele frequencies in admixed populations. We developed a method, ancestry-specific allele frequency estimation in admixed populations (AFA), to estimate the frequencies of biallelic variants in admixed populations with an unlimited number of ancestries, using either local or global proportion ancestries. Ancestry-specific allele frequencies can contribute to both research and personalized health of admixed populations.
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影响因子：
30.8
作者：
Atkinson EG;Maihofer AX;Kanai M;Martin AR;Karczewski KJ;Santoro ML;Ulirsch JC;Kamatani Y;Okada Y;Finucane HK;Koenen KC;Nievergelt CM;Daly MJ;Neale BM
通讯作者：
Neale BM
影响因子：
5.6
作者：
Lavange, Lisa M.;Kalsbeek, William D.;Sorlie, Paul D.;Aviles-Santa, Larissa M.;Kaplan, Robert C.;Barnhart, Janice;Liu, Kiang;Giachello, Aida;Lee, David J.;Ryan, John;Criqui, Michael H.;Elder, John P.
通讯作者：
Elder, John P.
影响因子：
3.7
作者：
Sofer T;Baier LJ;Browning SR;Thornton TA;Talavera GA;Wassertheil-Smoller S;Daviglus ML;Hanson R;Kobes S;Cooper RS;Cai J;Levy D;Reiner AP;Franceschini N
通讯作者：
Franceschini N
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 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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 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通讯作者：
Willer CJ
影响因子：
16.6
作者：
Ko A;Cantor RM;Weissglas-Volkov D;Nikkola E;Reddy PM;Sinsheimer JS;Pasaniuc B;Brown R;Alvarez M;Rodriguez A;Rodriguez-Guillen R;Bautista IC;Arellano-Campos O;Muñoz-Hernández LL;Salomaa V;Kaprio J;Jula A;Jauhiainen M;Heliövaara M;Raitakari O;Lehtimäki T;Eriksson JG;Perola M;Lohmueller KE;Matikainen N;Taskinen MR;Rodriguez-Torres M;Riba L;Tusie-Luna T;Aguilar-Salinas CA;Pajukanta P
通讯作者：
Pajukanta P