@article{9a5b6c6a6bd34223938757b55fd0ca4a,
title = "A unified framework identifies new links between plasma lipids and diseases from electronic medical records across large-scale cohorts",
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.",
author = "Yogasudha Veturi and Anastasia Lucas and Yuki Bradford and Daniel Hui and Scott Dudek and Elizabeth Theusch and Anurag Verma and Miller, {Jason E.} and Iftikhar Kullo and Hakon Hakonarson and Patrick Sleiman and Daniel Schaid and Stein, {Charles M.} and Edwards, {Digna R.Velez} and Feng, {Qi Ping} and Wei, {Wei Qi} and Medina, {Marisa W.} and Krauss, {Ronald M.} and Hoffmann, {Thomas J.} and Neil Risch and Voight, {Benjamin F.} and Rader, {Daniel J.} and Ritchie, {Marylyn D.}",
note = "Funding Information: Phase III of the eMERGE Network was initiated and funded by the NHGRI through the following grants: U01HG8657 (Group Health Cooperative/University of Washington); U01HG8685 (Brigham and Women{\textquoteright}s Hospital); U01HG8672 (Vanderbilt University Medical Center); U01HG8666 (Cincinnati Children{\textquoteright}s Hospital Medical Center); U01HG6379 (Mayo Clinic); U01HG8679 (Geisinger Clinic); U01HG8680 (Columbia University Health Sciences); U01HG8684 (Children{\textquoteright}s Hospital of Philadelphia); U01HG8673 (Northwestern University); U01HG8701 (Vanderbilt University Medical Center serving as the Coordinating Center); U01HG8676 (Partners Healthcare/Broad Institute); and U01HG8664 (Baylor College of Medicine). For the UKB, all data for this cohort pertained to project 32133: {\textquoteleft}Integration of multi-organ imaging phenotypes, clinical phenotypes and genomic data{\textquoteright}. Y.V., R.M.K., T.J.H., N.R., M.W.M., E.T. and M.D.R. acknowledge funding from the National Institutes of Health (NIH GM115318: Pharmacogenomics of Statin Therapy (POST)). Y.V. and M.D.R. also acknowledge NIH AI077505 (Pharmacogenomics of HIV Therapy). J.E.M. acknowledges NHGRI T32HG009495–01; C.M.S. acknowledges R35GM131770 (Pharmacogenetics to improve Drug Therapy). B.F.V. acknowledges NIH DK101478, NIH HG010067 and a Linda Pechenik Montague Investigator Award for their time on this project. Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2021",
month = jul,
doi = "10.1038/s41588-021-00879-y",
language = "English (US)",
volume = "53",
pages = "972--981",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "7",
}