The power of genetic diversity in genome-wide association studies of lipids
Graham, Sarah E. ; Poveda, Alaitz LU
; Kurbasic, Azra
LU
; Lyssenko, Valeriya
LU
; Franks, Paul
LU
and Willer, Cristen J.
(2021)
In Nature
600(7890).
p.675-679
- Abstract
- Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use1. Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels2, heart disease remains the leading cause of death worldwide3. 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 GWAS4–23 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... (More)
- Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use1. Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels2, heart disease remains the leading cause of death worldwide3. 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 GWAS4–23 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 patterns24. 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 medicine25, we anticipate that increased diversity of participants will lead to more accurate and equitable26 application of polygenic scores in clinical practice. © 2021, The Author(s), under exclusive licence to Springer Nature Limited. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/c735215c-2b87-4e5c-b138-c41944a1b9c9
- author
- Graham, Sarah E.
; Poveda, Alaitz
LU
; Kurbasic, Azra
LU
; Lyssenko, Valeriya
LU
; Franks, Paul
LU
and Willer, Cristen J.
- author collaboration
- organization
- publishing date
- 2021
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- allele, cardiovascular disease, cause of death, drug, genome, lipid, meta-analysis, risk factor
- in
- Nature
- volume
- 600
- issue
- 7890
- pages
- 5 pages
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85121605114
- pmid:34887591
- ISSN
- 0028-0836
- DOI
- 10.1038/s41586-021-04064-3
- language
- English
- LU publication?
- yes
- id
- c735215c-2b87-4e5c-b138-c41944a1b9c9
- date added to LUP
- 2022-02-04 09:05:26
- date last changed
- 2024-04-10 08:18:41
@article{c735215c-2b87-4e5c-b138-c41944a1b9c9,
abstract = {{Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use1. Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels2, heart disease remains the leading cause of death worldwide3. 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 GWAS4–23 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 patterns24. 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 medicine25, we anticipate that increased diversity of participants will lead to more accurate and equitable26 application of polygenic scores in clinical practice. © 2021, The Author(s), under exclusive licence to Springer Nature Limited.}},
author = {{Graham, Sarah E. and Poveda, Alaitz and Kurbasic, Azra and Lyssenko, Valeriya and Franks, Paul and Willer, Cristen J.}},
issn = {{0028-0836}},
keywords = {{allele; cardiovascular disease; cause of death; drug; genome; lipid; meta-analysis; risk factor}},
language = {{eng}},
number = {{7890}},
pages = {{675--679}},
publisher = {{Nature Publishing Group}},
series = {{Nature}},
title = {{The power of genetic diversity in genome-wide association studies of lipids}},
url = {{http://dx.doi.org/10.1038/s41586-021-04064-3}},
doi = {{10.1038/s41586-021-04064-3}},
volume = {{600}},
year = {{2021}},
}