A Unified Framework Identifies New Links Between Plasma Lipids and Diseases from Electronic Medical Records Across Large-scale Cohorts

Overview

Journal Nat Genet

Specialty Genetics

Date 2021 Jun 18

PMID 34140684

Citations 10

Authors

Yogasudha Veturi

Anastasia Lucas

Yuki Bradford

Daniel Hui

Scott Dudek

Elizabeth Theusch

Anurag Verma

Jason E Miller

Iftikhar Kullo

Hakon Hakonarson

Patrick Sleiman

Daniel Schaid

Charles M Stein

Digna R Velez Edwards

Qiping Feng

Wei-Qi Wei

Marisa W Medina

Ronald M Krauss

Thomas J Hoffmann

Neil Risch

Benjamin F Voight

Daniel J Rader

Marylyn D Ritchie

Affiliations

Soon will be listed here.

Abstract

Plasma lipids are known heritable risk factors for cardiovascular disease, but increasing evidence also supports shared genetics with diseases of other organ systems. We devised a comprehensive three-phase framework to identify new lipid-associated genes and study the relationships among lipids, genotypes, gene expression and hundreds of complex human diseases from the Electronic Medical Records and Genomics (347 traits) and the UK Biobank (549 traits). Aside from 67 new lipid-associated genes with strong replication, we found evidence for pleiotropic SNPs/genes between lipids and diseases across the phenome. These include discordant pleiotropy in the HLA region between lipids and multiple sclerosis and putative causal paths between triglycerides and gout, among several others. Our findings give insights into the genetic basis of the relationship between plasma lipids and diseases on a phenome-wide scale and can provide context for future prevention and treatment strategies.

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