Polygenic risk scores for disease risk prediction in Africa: current challenges and future directions.
Polygenic risk scores for disease risk prediction in Africa: current challenges and future directions.
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DOI：
10.1186/s13073-023-01245-9
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发表时间：
2023-10-30
期刊：
影响因子：
12.3
通讯作者：
Fakim, Yasmina Jaufeerally
中科院分区：
文献类型：
--
作者：
Fatumo, Segun;Sathan, Dassen;Samtal, Chaimae;Isewon, Itunuoluwa;Tamuhla, Tsaone;Soremekun, Chisom;Jafali, James;Panji, Sumir;Tiffin, Nicki;Fakim, Yasmina Jaufeerally
及早识别复杂疾病的遗传风险因素可以及时采取干预措施并预防严重后果，包括死亡。虽然许多孟德尔疾病的遗传学已被阐明，但由于许多遗传变异的综合影响而对疾病病因学的个体影响较小，因此预测复杂疾病的风险更加困难。多基因风险评分（PRS）结合了多个起作用的变异来预测疾病风险，有可能影响精准医疗的实施。然而，大多数现有的 PRS 都是根据欧洲数据开发的，对非洲人群的可移植性有限。值得注意的是，非洲人群具有不同的遗传背景，与欧洲基因组相比，其基因组结构具有更小的单倍型块。随后，越来越多的证据表明，使用大规模非洲血统队列作为 PRS 发展的发现可能会产生更普遍的发现。在这里，我们 (1) 讨论导致 PRS 在非洲人群中转移性差的因素，(2) 展示用于 PRS 开发的新型非洲基因组数据集，(3) 探索 PRS 在非洲人群中的潜在临床效用，以及 (4) 深入了解 PRS 在非洲的未来。在线版本包含可在 10.1186/s13073-023-01245-9 获取的补充材料。
Early identification of genetic risk factors for complex diseases can enable timely interventions and prevent serious outcomes, including mortality. While the genetics underlying many Mendelian diseases have been elucidated, it is harder to predict risk for complex diseases arising from the combined effects of many genetic variants with smaller individual effects on disease aetiology. Polygenic risk scores (PRS), which combine multiple contributing variants to predict disease risk, have the potential to influence the implementation for precision medicine. However, the majority of existing PRS were developed from European data with limited transferability to African populations. Notably, African populations have diverse genetic backgrounds, and a genomic architecture with smaller haplotype blocks compared to European genomes. Subsequently, growing evidence shows that using large-scale African ancestry cohorts as discovery for PRS development may generate more generalizable findings. Here, we (1) discuss the factors contributing to the poor transferability of PRS in African populations, (2) showcase the novel Africa genomic datasets for PRS development, (3) explore the potential clinical utility of PRS in African populations, and (4) provide insight into the future of PRS in Africa. The online version contains supplementary material available at 10.1186/s13073-023-01245-9.
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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
DOI：
10.1056/nejmsr1809937
发表时间：
2019-08-15
期刊：
The New England journal of medicine
影响因子：
--
作者：
All of Us Research Program Investigators;Denny JC;Rutter JL;Goldstein DB;Philippakis A;Smoller JW;Jenkins G;Dishman E
通讯作者：
Dishman E
影响因子：
64.5
作者：
Gurdasani, Deepti;Carstensen, Tommy;Sandhu, Manj S.
通讯作者：
Sandhu, Manj S.
影响因子：
16.6
作者：
Graff RE;Cavazos TB;Thai KK;Kachuri L;Rashkin SR;Hoffman JD;Alexeeff SE;Blatchins M;Meyers TJ;Leong L;Tai CG;Emami NC;Corley DA;Kushi LH;Ziv E;Van Den Eeden SK;Jorgenson E;Hoffmann TJ;Habel LA;Witte JS;Sakoda LC
通讯作者：
Sakoda LC
影响因子：
30.8
作者：
Cai N;Revez JA;Adams MJ;Andlauer TFM;Breen G;Byrne EM;Clarke TK;Forstner AJ;Grabe HJ;Hamilton SP;Levinson DF;Lewis CM;Lewis G;Martin NG;Milaneschi Y;Mors O;Müller-Myhsok B;Penninx BWJH;Perlis RH;Pistis G;Potash JB;Preisig M;Shi J;Smoller JW;Streit F;Tiemeier H;Uher R;Van der Auwera S;Viktorin A;Weissman MM;MDD Working Group of the Psychiatric Genomics Consortium;Kendler KS;Flint J
通讯作者：
Flint J