Dron Jacqueline S, Natarajan Pradeep, Peloso Gina M
Center for Genomic Medicine, Massachusetts General Hospital, Boston.
Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge.
Curr Opin Lipidol. 2025 Apr 1;36(2):61-70. doi: 10.1097/MOL.0000000000000966. Epub 2024 Dec 9.
This review highlights contributions of the Global Lipids Genetics Consortium (GLGC) in advancing the understanding of the genetic etiology of blood lipid traits, including total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, and non-HDL cholesterol. We emphasize the consortium's collaborative efforts, discoveries related to lipid and lipoprotein biology, methodological advancements, and utilization in areas extending beyond lipid research.
The GLGC has identified over 923 genomic loci associated with lipid traits through genome-wide association studies (GWASs), involving more than 1.65 million individuals from globally diverse populations. Many loci have been functionally validated by individuals inside and outside the GLGC community. Recent GLGC studies show increased population diversity enhances variant discovery, fine-mapping of causal loci, and polygenic score prediction for blood lipid levels. Moreover, publicly available GWAS summary statistics have facilitated the exploration of lipid-related genetic influences on cardiovascular and noncardiovascular diseases, with implications for therapeutic development and drug repurposing.
The GLGC has significantly advanced the understanding of the genetic basis of lipid levels and serves as the leading resource of GWAS summary statistics for these traits. Continued collaboration will be critical to further understand lipid and lipoprotein biology through large-scale genetic assessments in diverse populations.
本综述重点介绍全球脂质遗传学联盟（GLGC）在推进对血脂性状遗传病因的理解方面所做的贡献，这些血脂性状包括总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、甘油三酯和非高密度脂蛋白胆固醇。我们强调该联盟的合作努力、与脂质和脂蛋白生物学相关的发现、方法学进展以及在脂质研究以外领域的应用。
通过全基因组关联研究（GWAS），GLGC已鉴定出超过923个与血脂性状相关的基因组位点，涉及来自全球不同人群的165万多人。GLGC群体内外的研究人员已对许多位点进行了功能验证。GLGC最近的研究表明，增加群体多样性可提高变异发现、因果位点精细定位以及血脂水平多基因评分预测的能力。此外，公开可用的GWAS汇总统计数据有助于探索脂质相关遗传因素对心血管疾病和非心血管疾病的影响，对治疗开发和药物再利用具有重要意义。
GLGC极大地推进了对血脂水平遗传基础的理解，是这些性状GWAS汇总统计数据的主要来源。通过对不同人群进行大规模遗传评估，持续开展合作对于进一步了解脂质和脂蛋白生物学至关重要。
