Ancestry deconvolution and partial polygenic score can improve susceptibility predictions in recently admixed individuals

被引:64
作者
Marnetto, Davide [1 ]
Parna, Katri [1 ,2 ,3 ]
Lall, Kristi [1 ]
Molinaro, Ludovica [1 ,2 ]
Montinaro, Francesco [1 ]
Haller, Toomas [1 ]
Metspalu, Mait [1 ]
Magi, Reedik [1 ]
Fischer, Krista [1 ,4 ]
Pagani, Luca [1 ,5 ]
机构
[1] Univ Tartu, Inst Genom, Riia 23b, EE-51010 Tartu, Estonia
[2] Univ Tartu, Inst Mol & Cell Biol, Riia 23, EE-51010 Tartu, Estonia
[3] Univ Med Ctr Groningen, Dept Epidemiol, Hanzepl 1, NL-9713 GZ Groningen, Netherlands
[4] Univ Tartu, Inst Math & Stat, Narva Mnt 18, EE-51009 Tartu, Estonia
[5] Univ Padua, Dept Biol, Via Ugo Bassi 58-B, I-35131 Padua, Italy
基金
欧盟地平线“2020”;
关键词
RISK PREDICTION; GENETIC RISK; ASSOCIATION;
D O I
10.1038/s41467-020-15464-w
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Polygenic Scores (PSs) describe the genetic component of an individual's quantitative phenotype or their susceptibility to diseases with a genetic basis. Currently, PSs rely on population-dependent contributions of many associated alleles, with limited applicability to understudied populations and recently admixed individuals. Here we introduce a combination of local ancestry deconvolution and partial PS computation to account for the population-specific nature of the association signals in individuals with admixed ancestry. We demonstrate partial PS to be a proxy for the total PS and that a portion of the genome is enough to improve susceptibility predictions for the traits we test. By combining partial PSs from different populations, we are able to improve trait predictability in admixed individuals with some European ancestry. These results may extend the applicability of PSs to subjects with a complex history of admixture, where current methods cannot be applied. Polygenic scores are believed to hold future promise for trait prediction and personalized medicine, but are sensitive to demographic history. Here, Marnetto et al. develop partial polygenic scores supplemented with local ancestry deconvolution which improves prediction accuracy into recently admixed European populations.
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页数:9
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