Increased blood lipid levels are heritable risk factors of
cardiovascular disease with varied prevalence worldwide owing to
different dietary patterns and medication use(1). Despite advances in
prevention and treatment, in particular through reducing low-density
lipoprotein cholesterol levels(2), heart disease remains the leading
cause of death worldwide(3). Genome-wideassociation 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(4-23) 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(24). 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(25), we
anticipate that increased diversity of participants will lead to more
accurate and equitable(26) application of polygenic scores in clinical
practice
