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Bispebjerg Hospital - en del af Københavns Universitetshospital
Udgivet

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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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  • Sarah E Graham
  • Shoa L Clarke
  • Kuan-Han H Wu
  • Stavroula Kanoni
  • Greg J M Zajac
  • Shweta Ramdas
  • Ida Surakka
  • Ioanna Ntalla
  • Sailaja Vedantam
  • Thomas W Winkler
  • Adam E Locke
  • Eirini Marouli
  • Mi Yeong Hwang
  • Sohee Han
  • Akira Narita
  • Ananyo Choudhury
  • Amy R Bentley
  • Kenneth Ekoru
  • Anurag Verma
  • Bhavi Trivedi
  • Hilary C Martin
  • Karen A Hunt
  • Qin Hui
  • Derek Klarin
  • Xiang Zhu
  • Gudmar Thorleifsson
  • Anna Helgadottir
  • Daniel F Gudbjartsson
  • Hilma Holm
  • Isleifur Olafsson
  • Masato Akiyama
  • Saori Sakaue
  • Chikashi Terao
  • Masahiro Kanai
  • Wei Zhou
  • Ben M Brumpton
  • Humaira Rasheed
  • Sanni E Ruotsalainen
  • Aki S Havulinna
  • Yogasudha Veturi
  • QiPing Feng
  • Mette Aadahl
  • Jette Bork-Jensen
  • Line L Kårhus
  • Line T Møllehave
  • Betina H Thuesen
  • Henrik Vestergaard
  • Torben Hansen
  • Allan Linneberg
  • Thomas M Dantoft
  • VA Million Veteran Program
Vis graf over relationer

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.

OriginalsprogEngelsk
TidsskriftNature
Vol/bind600
Udgave nummer7890
Sider (fra-til)675-679
Antal sider5
ISSN0028-0836
DOI
StatusUdgivet - 23 dec. 2021

Bibliografisk note

© 2021. The Author(s), under exclusive licence to Springer Nature Limited.

ID: 69934963