Variable prediction accuracy of polygenic scores within an ancestry group

被引:245
作者
Mostafavi, Hakhamanesh [1 ,4 ]
Harpak, Arbel [1 ]
Agarwal, Ipsita [1 ]
Conley, Dalton [2 ,3 ]
Pritchard, Jonathan K. [4 ,5 ,6 ]
Przeworski, Molly [1 ,7 ]
机构
[1] Columbia Univ, Dept Biol Sci, New York, NY 10027 USA
[2] Princeton Univ, Dept Sociol, Princeton, NJ 08544 USA
[3] Princeton Univ, Off Populat Res, Princeton, NJ 08544 USA
[4] Stanford Univ, Dept Genet, Stanford, CA 94305 USA
[5] Stanford Univ, Dept Biol, Stanford, CA 94305 USA
[6] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA
[7] Columbia Univ, Dept Syst Biol, New York, NY 10027 USA
基金
英国医学研究理事会;
关键词
GENOME-WIDE ASSOCIATION; FAST-LMM-SELECT; RISK PREDICTION; LINKAGE DISEQUILIBRIUM; SPATIAL STRUCTURE; HERITABILITY; LOCI; ARCHITECTURE; METAANALYSIS; ADAPTATION;
D O I
10.7554/eLife.48376
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Fields as diverse as human genetics and sociology are increasingly using polygenic scores based on genome-wide association studies (GWAS) for phenotypic prediction. However, recent work has shown that polygenic scores have limited portability across groups of different genetic ancestries, restricting the contexts in which they can be used reliably and potentially creating serious inequities in future clinical applications. Using the UK Biobank data, we demonstrate that even within a single ancestry group (i.e., when there are negligible differences in linkage disequilibrium or in causal alleles frequencies), the prediction accuracy of polygenic scores can depend on characteristics such as the socio-economic status, age or sex of the individuals in which the GWAS and the prediction were conducted, as well as on the GWAS design. Our findings highlight both the complexities of interpreting polygenic scores and underappreciated obstacles to their broad use.
引用
收藏
页数:52
相关论文
共 91 条
[1]   A GWAS in Latin Americans highlights the convergent evolution of lighter skin pigmentation in Eurasia [J].
Adhikari, Kaustubh ;
Mendoza-Revilla, Javier ;
Sohail, Anood ;
Fuentes-Guajardo, Macarena ;
Lampert, Jodie ;
Chacon-Duque, Juan Camilo ;
Hurtado, Malena ;
Villegas, Valeria ;
Granja, Vanessa ;
Acuna-Alonzo, Victor ;
Jaramillo, Claudia ;
Arias, William ;
Barquera Lozano, Rodrigo ;
Everardo, Paola ;
Gomez-Valdes, Jorge ;
Villamil-Ramirez, Hugo ;
Silva de Cerqueira, Caio C. ;
Hunemeier, Tabita ;
Ramallo, Virginia ;
Schuler-Faccini, Lavinia ;
Salzano, Francisco M. ;
Gonzalez-Jose, Rolando ;
Bortolini, Maria-Catira ;
Canizales-Quinteros, Samuel ;
Gallo, Carla ;
Poletti, Giovanni ;
Bedoya, Gabriel ;
Rothhammer, Francisco ;
Tobin, Desmond J. ;
Fumagalli, Matteo ;
Balding, David ;
Ruiz-Linares, Andres .
NATURE COMMUNICATIONS, 2019, 10 (1)
[2]  
[Anonymous], 2018, BIORXIV, DOI DOI 10.1101/398396
[3]  
[Anonymous], 1984, APPL LINEAR MODELS A
[4]  
[Anonymous], 2018, BIORXIV, DOI [10.1101/260463, DOI 10.1101/260463]
[5]  
[Anonymous], BIORXIV, DOI [10.1101/485441, DOI 10.1101/485441]
[6]   Genetic analysis of social-class mobility in five longitudinal studies [J].
Belsky, Daniel W. ;
Domingue, Benjamin W. ;
Wedow, Robbee ;
Arseneault, Louise ;
Boardman, Jason D. ;
Caspi, Avshalom ;
Conley, Dalton ;
Fletcher, Jason M. ;
Freese, Jeremy ;
Herd, Pamela ;
Moffitt, Terrie E. ;
Poulton, Richie ;
Sicinski, Kamil ;
Wertz, Jasmin ;
Harris, Kathleen Mullan .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2018, 115 (31) :E7275-E7284
[7]   Multi-ancestry genome-wide gene-smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids [J].
Bentley, Amy R. ;
Sung, Yun J. ;
Brown, Michael R. ;
Winkler, Thomas W. ;
Kraja, Aldi T. ;
Ntalla, Ioanna ;
Schwander, Karen ;
Chasman, Daniel, I ;
Lim, Elise ;
Deng, Xuan ;
Guo, Xiuqing ;
Liu, Jingmin ;
Lu, Yingchang ;
Cheng, Ching-Yu ;
Sim, Xueling ;
Vojinovic, Dina ;
Huffman, Jennifer E. ;
Musani, Solomon K. ;
Li, Changwei ;
Feitosa, Mary F. ;
Richard, Melissa A. ;
Noordam, Raymond ;
Baker, Jenna ;
Chen, Guanjie ;
Aschard, Hugues ;
Bartz, Traci M. ;
Ding, Jingzhong ;
Dorajoo, Rajkumar ;
Manning, Alisa K. ;
Rankinen, Tuomo ;
Smith, Albert, V ;
Tajuddin, Salman M. ;
Zhao, Wei ;
Graff, Mariaelisa ;
Alver, Maris ;
Boissel, Mathilde ;
Chai, Jin Fang ;
Chen, Xu ;
Divers, Jasmin ;
Evangelou, Evangelos ;
Gao, Chuan ;
Goel, Anuj ;
Hagemeijer, Yanick ;
Harris, Sarah E. ;
Hartwig, Fernando P. ;
He, Meian ;
Horimoto, Andrea R. V. R. ;
Hsu, Fang-Chi ;
Hung, Yi-Jen ;
Jackson, Anne U. .
NATURE GENETICS, 2019, 51 (04) :636-+
[8]   A Population Genetic Signal of Polygenic Adaptation [J].
Berg, Jeremy J. ;
Coop, Graham .
PLOS GENETICS, 2014, 10 (08)
[9]   The Future of Genomic Studies Must Be Globally Representative: Perspectives from PAGE [J].
Bien, Stephanie A. ;
Wojcik, Genevieve L. ;
Hodonsky, Chani J. ;
Gignoux, Christopher R. ;
Cheng, Iona ;
Matise, Tara C. ;
Peters, Ulrike ;
Kenny, Eimear E. ;
North, Kari E. .
ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS, VOL 20, 2019, 2019, 20 :181-200
[10]   An Expanded View of Complex Traits: From Polygenic to Omnigenic [J].
Boyle, Evan A. ;
Li, Yang I. ;
Pritchard, Jonathan K. .
CELL, 2017, 169 (07) :1177-1186