Maldonado Betzaida L, Piqué Daniel G, Kaplan Robert C, Claw Katrina G, Gignoux Christopher R
Human Medical Genetics & Genomics Graduate Program, University of Colorado-Anschutz Medical Campus, Aurora, CO, USA.
Colorado Center for Personalized Medicine, University of Colorado-Anschutz Medical Campus, Aurora, CO, USA.
J Community Genet. 2023 Dec;14(6):543-553. doi: 10.1007/s12687-023-00686-4. Epub 2023 Nov 14.
Genome-wide association studies (GWAS) have allowed the identification of disease-associated variants, which can be leveraged to build polygenic scores (PGSs). Even though PGSs can be a valuable tool in personalized medicine, their predictive power is limited in populations of non-European ancestry, particularly in admixed populations. Recent efforts have focused on increasing racial and ethnic diversity in GWAS, thus, addressing some of the limitations of genetic risk prediction in these populations. Even with these efforts, few studies focus exclusively on Hispanics/Latinos. Additionally, Hispanic/Latino populations are often considered a single population despite varying admixture proportions between and within ethnic groups, diverse genetic heterogeneity, and demographic history. Combined with highly heterogeneous environmental and socioeconomic exposures, this diversity can reduce the transferability of genetic risk prediction models. Given the recent increase of genomic studies that include Hispanics/Latinos, we review the milestones and efforts that focus on genetic risk prediction, summarize the potential for improving PGS transferability, and highlight the challenges yet to be addressed. Additionally, we summarize social-ethical considerations and provide ideas to promote genetic risk prediction models that can be implemented equitably.
全基因组关联研究(GWAS)已使疾病相关变异得以识别,这些变异可用于构建多基因分数(PGS)。尽管PGS在个性化医疗中可能是一种有价值的工具,但其预测能力在非欧洲血统人群中有限,尤其是在混合人群中。最近的努力集中在增加GWAS中的种族和民族多样性,从而解决这些人群中遗传风险预测的一些局限性。即便有这些努力,很少有研究专门关注西班牙裔/拉丁裔人群。此外,尽管不同种族群体之间以及群体内部的混合比例不同、存在多样的遗传异质性和人口历史,但西班牙裔/拉丁裔人群通常被视为单一群体。这种多样性与高度异质的环境和社会经济暴露相结合,会降低遗传风险预测模型的可转移性。鉴于近期纳入西班牙裔/拉丁裔人群的基因组研究有所增加,我们回顾了专注于遗传风险预测的里程碑和努力,总结了提高PGS可转移性的潜力,并强调了有待解决的挑战。此外,我们总结了社会伦理考量,并提供了促进可公平实施的遗传风险预测模型的思路。