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A large electronic-health-record-based genome-wide study of serum lipids
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Journal Article
A large electronic-health-record-based genome-wide study of serum lipids
2018
Overview
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.
Genome-wide association analysis using electronic health record data from >94,000 individuals identifies loci associated with plasma lipid concentrations. Longitudinal measurements allow for the calculation of genetic risk scores and increase the variance explained.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ 45/43
/ Adult
/ Aged
/ Animal Genetics and Genomics
/ Asians
/ Biomedical and Life Sciences
/ Electronic Health Records - statistics & numerical data
/ Ethnic Groups - statistics & numerical data
/ Female
/ Genes
/ Genome-Wide Association Study - methods
/ Genomes
/ Genomics
/ Health
/ Health maintenance organizations
/ Humans
/ Lipids
/ Liver
/ Male
/ Pharmacy
