Naslov
The power of genetic diversity in genome-wide association studies of lipids

Autori
Graham, Sarah E. ; … ; Kolcic, Ivana ; Polasek, Ozren ; … Chasman, Daniel, I

Kolaboracija
VA Million Veteran Program ; Global Lipids Genetics Consortium

Izvornik
Nature (0028-0836) 600 (2021), 7890; 675-679

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Cardiovascular Diseases ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Linkage Disequilibrium ; Multifactorial Inheritance ; Polymorphism, Single Nucleotide

Sažetak
Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use. Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels, heart disease remains the leading cause of death worldwide. Genome-wide association studies (GWAS) of blood lipid levels have led to important biological and clinical insights, as well as new drug targets, for cardiovascular disease. However, most previous GWAS have been conducted in European ancestry populations and may have missed genetic variants that contribute to lipid-level variation in other ancestry groups. These include differences in allele frequencies, effect sizes and linkage-disequilibrium patterns. Here we conduct a multi-ancestry, genome-wide genetic discovery meta-analysis of lipid levels in approximately 1.65 million individuals, including 350, 000 of non-European ancestries. We quantify the gain in studying non-European ancestries and provide evidence to support the expansion of recruitment of additional ancestries, even with relatively small sample sizes. We find that increasing diversity rather than studying additional individuals of European ancestry results in substantial improvements in fine- mapping functional variants and portability of polygenic prediction (evaluated in approximately 295, 000 individuals from 7 ancestry groupings). Modest gains in the number of discovered loci and ancestry-specific variants were also achieved. As GWAS expand emphasis beyond the identification of genes and fundamental biology towards the use of genetic variants for preventive and precision medicine, we anticipate that increased diversity of participants will lead to more accurate and equitable application of polygenic scores in clinical practice.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA