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A large electronic-health-record-based genome-wide study of serum lipids

Nature genetics, 2018-03, Vol.50 (3), p.401-413 [Peer Reviewed Journal]

COPYRIGHT 2018 Nature Publishing Group ;COPYRIGHT 2018 Nature Publishing Group ;ISSN: 1061-4036 ;EISSN: 1546-1718 ;DOI: 10.1038/s41588-018-0064-5 ;PMID: 29507422

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Title:
A large electronic-health-record-based genome-wide study of serum lipids
Author: Hoffmann, Thomas J ; Theusch, Elizabeth ; Haldar, Tanushree ; Ranatunga, Dilrini K ; Jorgenson, Eric ; Medina, Marisa W ; Kvale, Mark N ; Kwok, Pui-Yan ; Schaefer, Catherine ; Krauss, Ronald M ; Iribarren, Carlos ; Risch, Neil
Subjects: African Americans ; Analysis and chemistry ; Anticholesteremic agents ; Asians ; Blood ; Blood lipids ; Cholesterol ; Cholesterol tests ; Coronary heart disease ; Drugstores ; Electronic records ; Genes ; Genetic research ; Genomes ; Genomics ; Health ; Health maintenance organizations ; Heart diseases ; Lipids ; Liver ; Low density lipoproteins ; Medical records ; Pharmacy ; Triglycerides
Is Part Of: Nature genetics, 2018-03, Vol.50 (3), p.401-413
Description: A genome-wide association study (GWAS) of 94,674 ancestrally diverse Kaiser Permanente members using 478,866 longitudinal electronic health record (EHR)-derived measurements for untreated serum lipid levels empowered multiple new findings: 121 new SNP associations (46 primary, 15 conditional, and 60 in meta-analysis with Global Lipids Genetic Consortium data); an increase of 33-42% in variance explained with multiple measurements; sex differences in genetic impact (greater impact in females for LDL, HDL, and total cholesterol and the opposite for triglycerides); differences in variance explained among non-Hispanic whites, Latinos, African Americans, and East Asians; genetic dominance and epistatic interaction, with strong evidence for both at the ABO and FUT2 genes for LDL; and tissue-specific enrichment of GWAS-associated SNPs among liver, adipose, and pancreas eQTLs. Using EHR pharmacy data, both LDL and triglyceride genetic risk scores (477 SNPs) were strongly predictive of age at initiation of lipid-lowering treatment. These findings highlight the value of longitudinal EHRs for identifying new genetic features of cholesterol and lipoprotein metabolism with implications for lipid treatment and risk of coronary heart disease.
Publisher: United States: Nature Publishing Group
Language: English
Identifier: ISSN: 1061-4036
EISSN: 1546-1718
DOI: 10.1038/s41588-018-0064-5
PMID: 29507422
Source: GFMER Free Medical Journals
ProQuest Central

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A large electronic-health-record-based genome-wide study of serum lipids

COPYRIGHT 2018 Nature Publishing Group ;COPYRIGHT 2018 Nature Publishing Group ;ISSN: 1061-4036 ;EISSN: 1546-1718 ;DOI: 10.1038/s41588-018-0064-5 ;PMID: 29507422

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