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

A genome-wide association study of 94,674 multi-ethnic Kaiser Permanente members utilizing 478,866 longitudinal untreated serum lipid electronic-health-record-derived measurements (EHRs) empowered multiple novel findings: 121 new SNP associations (46 primary, 15 conditional, 60 in meta-analysis with...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2018
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5942247/
https://www.ncbi.nlm.nih.gov/pubmed/29507422
http://dx.doi.org/10.1038/s41588-018-0064-5
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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
author_facet 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
author_sort Hoffmann, Thomas J
collection PubMed
description A genome-wide association study of 94,674 multi-ethnic Kaiser Permanente members utilizing 478,866 longitudinal untreated serum lipid electronic-health-record-derived measurements (EHRs) empowered multiple novel findings: 121 new SNP associations (46 primary, 15 conditional, 60 in meta-analysis with Global Lipids Genetic Consortium); increase of 33-42% in variance explained with multiple measurements; sex differences in genetic impact (greater in females for LDL, HDL, TC, the opposite for TG); differences in variance explained amongst non-Hispanic whites, Latinos, African Americans, and East Asians; genetic dominance and epistasis, with strong evidence for both at ABOxFUT2 for LDL; and eQTL tissue-enrichment implicating the liver, adipose, and pancreas. Utilizing EHR pharmacy data, both LDL and TG 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 novel genetic features of cholesterol and lipoprotein metabolism with implications for lipid treatment and risk of coronary heart disease.
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spelling pubmed-59422472018-09-05 A large electronic health record-based genome-wide study of serum lipids 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 Nat Genet Article A genome-wide association study of 94,674 multi-ethnic Kaiser Permanente members utilizing 478,866 longitudinal untreated serum lipid electronic-health-record-derived measurements (EHRs) empowered multiple novel findings: 121 new SNP associations (46 primary, 15 conditional, 60 in meta-analysis with Global Lipids Genetic Consortium); increase of 33-42% in variance explained with multiple measurements; sex differences in genetic impact (greater in females for LDL, HDL, TC, the opposite for TG); differences in variance explained amongst non-Hispanic whites, Latinos, African Americans, and East Asians; genetic dominance and epistasis, with strong evidence for both at ABOxFUT2 for LDL; and eQTL tissue-enrichment implicating the liver, adipose, and pancreas. Utilizing EHR pharmacy data, both LDL and TG 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 novel genetic features of cholesterol and lipoprotein metabolism with implications for lipid treatment and risk of coronary heart disease. 2018-03-05 2018-03 /pmc/articles/PMC5942247/ /pubmed/29507422 http://dx.doi.org/10.1038/s41588-018-0064-5 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
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
A large electronic health record-based genome-wide study of serum lipids
title A large electronic health record-based genome-wide study of serum lipids
title_full A large electronic health record-based genome-wide study of serum lipids
title_fullStr A large electronic health record-based genome-wide study of serum lipids
title_full_unstemmed A large electronic health record-based genome-wide study of serum lipids
title_short A large electronic health record-based genome-wide study of serum lipids
title_sort large electronic health record-based genome-wide study of serum lipids
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5942247/
https://www.ncbi.nlm.nih.gov/pubmed/29507422
http://dx.doi.org/10.1038/s41588-018-0064-5
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