Imputation Performance in Latin American Populations: Improving Rare Variants Representation With the Inclusion of Native American Genomes.
Imputation Performance in Latin American Populations: Improving Rare Variants Representation With the Inclusion of Native American Genomes.
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DOI：
10.3389/fgene.2021.719791
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发表时间：
2021
影响因子：
3.7
通讯作者：
Moreno-Estrada A
中科院分区：
文献类型：
--
作者：
Jiménez-Kaufmann A;Chong AY;Cortés A;Quinto-Cortés CD;Fernandez-Valverde SL;Ferreyra-Reyes L;Cruz-Hervert LP;Medina-Muñoz SG;Sohail M;Palma-Martinez MJ;Delgado-Sánchez G;Mongua-Rodríguez N;Mentzer AJ;Hill AVS;Moreno-Macías H;Huerta-Chagoya A;Aguilar-Salinas CA;Torres M;Kim HL;Kalsi N;Schuster SC;Tusié-Luna T;Del-Vecchyo DO;García-García L;Moreno-Estrada A
目前的全基因组关联研究（GWAS）依赖于基因型插补来增加统计功效，改善关联信号的精细映射，并促进荟萃分析。由于拉丁美洲复杂的人口统计学历史，以及在目前的插补小组中缺乏美洲原住民基因组的平衡代表性，可能会错过当地相关疾病变异的发现，从而限制了这些人群生物医学研究的范围和影响。因此，在基因组数据库中更好地表示多样性的必要性是科学的当务之急。在这里，我们扩展了1,000个基因组参考面板（1 KGP），其中包含134个美洲原住民基因组（1 KGP + NAT），以评估拉丁美洲混合血统个体的插补性能。我们的小组增加了超过GWAS质量阈值的SNP数量，从而提高了该地区关联研究的统计能力。它还提高了插补的准确性，特别是在美洲原住民祖先区域中分离的低频变异中。这种改善是微妙的，但在各国之间是一致的，并且与从当地来源人群添加的基因组数量成比例。为了用更多的参考基因组来预测潜在的改进，我们进行了模拟，发现至少需要3,000个美洲原住民基因组才能等同于欧洲祖先区域中变异的插补性能。这反映了当前参考文献中令人担忧的多样性不平衡，并突出了我们的工作对减少多样性的贡献，同时补充了改善基因组研究全球公平性的努力。
Current Genome-Wide Association Studies (GWAS) rely on genotype imputation to increase statistical power, improve fine-mapping of association signals, and facilitate meta-analyses. Due to the complex demographic history of Latin America and the lack of balanced representation of Native American genomes in current imputation panels, the discovery of locally relevant disease variants is likely to be missed, limiting the scope and impact of biomedical research in these populations. Therefore, the necessity of better diversity representation in genomic databases is a scientific imperative. Here, we expand the 1,000 Genomes reference panel (1KGP) with 134 Native American genomes (1KGP + NAT) to assess imputation performance in Latin American individuals of mixed ancestry. Our panel increased the number of SNPs above the GWAS quality threshold, thus improving statistical power for association studies in the region. It also increased imputation accuracy, particularly in low-frequency variants segregating in Native American ancestry tracts. The improvement is subtle but consistent across countries and proportional to the number of genomes added from local source populations. To project the potential improvement with a higher number of reference genomes, we performed simulations and found that at least 3,000 Native American genomes are needed to equal the imputation performance of variants in European ancestry tracts. This reflects the concerning imbalance of diversity in current references and highlights the contribution of our work to reducing it while complementing efforts to improve global equity in genomic research.
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影响因子：
64.8
作者：
Gurdasani, Deepti;Carstensen, Tommy;Tekola-Ayele, Fasil;Pagani, Luca;Tachmazidou, Ioanna;Hatzikotoulas, Konstantinos;Karthikeyan, Savita;Iles, Louise;Pollard, Martin O.;Choudhury, Ananyo;Ritchie, GrahamR. S.;Xue, Yali;Asimit, Jennifer;Nsubuga, Rebecca N.;Young, Elizabeth H.;Pomilla, Cristina;Kivinen, Katja;Rockett, Kirk;Kamali, Anatoli;Doumatey, Ayo P.;Asiki, Gershim;Seeley, Janet;Sisay-Joof, Fatoumatta;Jallow, Muminatou;Tollman, Stephen;Mekonnen, Ephrem;Ekong, Rosemary;Oljira, Tamiru;Bradman, Neil;Bojang, Kalifa;Ramsay, Michele;Adeyemo, Adebowale;Bekele, Endashaw;Motala, Ayesha;Norris, Shane A.;Pirie, Fraser;Kaleebu, Pontiano;Kwiatkowski, Dominic;Tyler-Smith, Chris;Rotimi, Charles;Zeggini, Eleftheria;Sandhu, Manjinder S.
通讯作者：
Sandhu, Manjinder S.
影响因子：
30.8
作者：
Flannick, Jason;Thorleifsson, Gudmar;Beer, Nicola L.;Jacobs, Suzanne B. R.;Grarup, Niels;Burtt, Noel P.;Mahajan, Anubha;Fuchsberger, Christian;Atzmon, Gil;Benediktsson, Rafn;Blangero, John;Bowden, Don W.;Brandslund, Ivan;Brosnan, Julia;Burslem, Frank;Chambers, John;Cho, Yoon Shin;Christensen, Cramer;Douglas, Desiree A.;Duggirala, Ravindranath;Dymek, Zachary;Farjoun, Yossi;Fennell, Timothy;Fontanillas, Pierre;Forsen, Tom;Gabriel, Stacey;Glaser, Benjamin;Gudbjartsson, Daniel F.;Hanis, Craig;Hansen, Torben;Hreidarsson, Astradur B.;Hveem, Kristian;Ingelsson, Erik;Isomaa, Bo;Johansson, Stefan;Jorgensen, Torben;Jorgensen, Marit Eika;Kathiresan, Sekar;Kong, Augustine;Kooner, Jaspal;Kravic, Jasmina;Laakso, Markku;Lee, Jong-Young;Lind, Lars;Lindgren, Cecilia M.;Linneberg, Allan;Masson, Gisli;Meitinger, Thomas;Mohlke, Karen L.;Molven, Anders;Morris, Andrew P.;Potluri, Shobha;Rauramaa, Rainer;Ribel-Madsen, Rasmus;Richard, Ann-Marie;Rolph, Tim;Salomaa, Veikko;Segre, Ayellet V.;Skaerstrand, Hanna;Steinthorsdottir, Valgerdur;Stringham, Heather M.;Sulem, Patrick;Tai, E. Shyong;Teo, Yik Ying;Teslovich, Tanya;Thorsteinsdottir, Unnur;Trimmer, Jeff K.;Tuomi, Tiinamaija;Tuomilehto, Jaakko;Vaziri-Sani, Fariba;Voight, Benjamin F.;Wilson, James G.;Boehnke, Michael;McCarthy, Mark I.;Njolstad, Pal R.;Pedersen, Oluf;Groop, Leif;Cox, David R.;Stefansson, Kari;Altshuler, David
通讯作者：
Altshuler, David
影响因子：
4.3
作者：
Kelleher J;Etheridge AM;McVean G
通讯作者：
McVean G
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：
16.6
作者：
Duncan, L.;Shen, H.;Domingue, B.
通讯作者：
Domingue, B.