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Predictive Utility of Polygenic Risk Scores for Coronary Heart Disease in Three Major Racial and Ethnic Groups.
American Journal of Human Genetics ( IF 8.1 ) Pub Date : 2020-05-07 , DOI: 10.1016/j.ajhg.2020.04.002
Ozan Dikilitas 1 , Daniel J Schaid 2 , Matthew L Kosel 2 , Robert J Carroll 3 , Christopher G Chute 4 , Joshua A Denny 3 , Alex Fedotov 5 , QiPing Feng 6 , Hakon Hakonarson 7 , Gail P Jarvik 8 , Ming Ta Michael Lee 9 , Jennifer A Pacheco 10 , Robb Rowley 11 , Patrick M Sleiman 7 , C Michael Stein 6 , Amy C Sturm 9 , Wei-Qi Wei 3 , Georgia L Wiesner 12 , Marc S Williams 9 , Yanfei Zhang 9 , Teri A Manolio 11 , Iftikhar J Kullo 1
Affiliation  

Because polygenic risk scores (PRSs) for coronary heart disease (CHD) are derived from mainly European ancestry (EA) cohorts, their validity in African ancestry (AA) and Hispanic ethnicity (HE) individuals is unclear. We investigated associations of "restricted" and genome-wide PRSs with CHD in three major racial and ethnic groups in the U.S. The eMERGE cohort (mean age 48 ± 14 years, 58% female) included 45,645 EA, 7,597 AA, and 2,493 HE individuals. We assessed two restricted PRSs (PRSTikkanen and PRSTada; 28 and 50 variants, respectively) and two genome-wide PRSs (PRSmetaGRS and PRSLDPred; 1.7 M and 6.6 M variants, respectively) derived from EA cohorts. Over a median follow-up of 11.1 years, 2,652 incident CHD events occurred. Hazard and odds ratios for the association of PRSs with CHD were similar in EA and HE cohorts but lower in AA cohorts. Genome-wide PRSs were more strongly associated with CHD than restricted PRSs were. PRSmetaGRS, the best performing PRS, was associated with CHD in all three cohorts; hazard ratios (95% CI) per 1 SD increase were 1.53 (1.46-1.60), 1.53 (1.23-1.90), and 1.27 (1.13-1.43) for incident CHD in EA, HE, and AA individuals, respectively. The hazard ratios were comparable in the EA and HE cohorts (pinteraction = 0.77) but were significantly attenuated in AA individuals (pinteraction= 2.9 × 10-3). These results highlight the potential clinical utility of PRSs for CHD as well as the need to assemble diverse cohorts to generate ancestry- and ethnicity PRSs.

中文翻译:

在三个主要种族和族裔群体中对冠心病使用多基因风险评分的预测效用。

由于冠心病(CHD)的多基因风险评分(PRS)主要来自欧洲血统(EA)队列,因此在非洲血统(AA)和西班牙裔(HE)个人中的有效性尚不清楚。我们调查了美国三个主要种族和族裔群体中“受限”和全基因组PRS与冠心病的关联。eMERGE队列(平均年龄48±14岁,女性占58%)包括45,645 EA,7,597 AA和2,493 HE个个体。我们评估了两个来自EA队列的限制性PRS(分别为PRSTikkanen和PRSTada;分别为28和50个变体)和两个全基因组PRS(分别为PRSmetaGRS和PRSLDPred;分别为1.7 M和6.6 M)。在11.1年的中位随访中,发生了2,652起冠心病事件。在EA和HE队列中,PRS与CHD关联的危险和优势比相似,但在AA队列中较低。全基因组PRS与冠心病的相关性比限制性PRS高。PRSmetaGRS是表现最好的PRS,在所有三个队列中均与CHD相关。EA,HE和AA个体发生CHD的风险每增加1 SD,危险比(95%CI)分别为1.53(1.46-1.60),1.53(1.23-1.90)和1.27(1.13-1.43)。在EA和HE队列中,危险比是可比的(交互作用= 0.77),而在AA个人中则明显降低(交互作用= 2.9×10-3)。这些结果凸显了PRS对CHD的潜在临床实用性,以及需要聚集不同的人群来产生祖先和种族PRS。全基因组PRS与冠心病的相关性比限制性PRS高。PRSmetaGRS是表现最好的PRS,在所有三个队列中均与CHD相关。EA,HE和AA个体发生CHD的风险每增加1 SD,危险比(95%CI)分别为1.53(1.46-1.60),1.53(1.23-1.90)和1.27(1.13-1.43)。在EA和HE队列中,危险比是可比的(交互作用= 0.77),而在AA个人中则明显降低(交互作用= 2.9×10-3)。这些结果凸显了PRS对CHD的潜在临床实用性,以及需要聚集不同的人群来产生祖先和种族PRS。全基因组PRS与冠心病的相关性比限制性PRS高。PRSmetaGRS是表现最好的PRS,在所有三个队列中均与CHD相关。EA,HE和AA个体发生CHD的风险每增加1 SD,危险比(95%CI)分别为1.53(1.46-1.60),1.53(1.23-1.90)和1.27(1.13-1.43)。在EA和HE队列中,危险比是可比的(交互作用= 0.77),而在AA个人中则明显降低(交互作用= 2.9×10-3)。这些结果凸显了PRS对CHD的潜在临床实用性,以及需要聚集不同的人群来产生祖先和种族PRS。43)分别针对EA,HE和AA个人的CHD事件。在EA和HE队列中,危险比是可比的(交互作用= 0.77),而在AA个人中则明显降低(交互作用= 2.9×10-3)。这些结果凸显了PRS对CHD的潜在临床实用性,以及需要聚集不同的人群来产生祖先和种族PRS。43)分别针对EA,HE和AA个人的CHD事件。在EA和HE队列中,危险比是可比的(交互作用= 0.77),而在AA个人中则明显降低(交互作用= 2.9×10-3)。这些结果凸显了PRS对CHD的潜在临床实用性,以及需要聚集不同的人群来产生祖先和种族PRS。
更新日期:2020-05-07
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