Open AccessA unified framework identifies new links between plasma lipids and diseases from electronic medical records across large-scale cohorts
Author(s) -
Yogasudha Veturi,
Anastasia Lucas,
Yuki Bradford,
Daniel Hui,
Scott M. Dudek,
Elizabeth Theusch,
Anurag Verma,
Jason E. Miller,
Iftikhar J. Kullo,
Hákon Hákonarson,
Patrick Sleiman,
Daniel J. Schaid,
C. Michael Stein,
Digna R. Velez Edwards,
Feng Qi,
Wei Qi Wei,
Marisa W. Medina,
Ronald M. Krauss,
Thomas J. Hoffmann,
Neil Risch,
Benjamin F. Voight,
Daniel J. Rader,
Marylyn D. Ritchie
Publication year - 2021
Publication title -
nature genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 18.861
H-Index - 573
eISSN - 1546-1718
pISSN - 1061-4036
DOI - 10.1038/s41588-021-00879-y
Subject(s) - phenome , biology , pleiotropy , context (archaeology) , biobank , expression quantitative trait loci , genetics , disease , genome wide association study , genomics , single nucleotide polymorphism , computational biology , bioinformatics , gene , genotype , genome , medicine , phenotype , paleontology
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.