University of Oulu

Davis JP, Huyghe JR, Locke AE, Jackson AU, Sim X, Stringham HM, et al. (2017) Common, low-frequency, and rare genetic variants associated with lipoprotein subclasses and triglyceride measures in Finnish men from the METSIM study. PLoS Genet 13(10): e1007079. https://doi.org/10.1371/journal.pgen.1007079

Common, low-frequency, and rare genetic variants associated with lipoprotein subclasses and triglyceride measures in Finnish men from the METSIM study

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Author: Davis, James P.1; Huyghe, Jeroen R.2; Locke, Adam E.2;
Organizations: 1Department of Genetics, University of North Carolina at Chapel Hill
2Department of Biostatistics and Center for Statistical Genetics, University of Michigan
3National Human Genome Research Institute, National Institutes of Health, Bethesda, MD
4Computational Medicine, Faculty of Medicine, University of Oulu
5Biocenter Oulu
6NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland
7Population Health Science, Bristol Medical School, University of Bristol
8Medical Research Council Integrative Epidemiology Unit at the University of Bristol
9Systems Epidemiology, Baker Heart and Diabetes Institute
10Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University
11Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland
12Kuopio University Hospital
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 5.2 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2017120555338
Language: English
Published: Public Library of Science, 2017
Publish Date: 2017-12-05
Description:

Abstract

Lipid and lipoprotein subclasses are associated with metabolic and cardiovascular diseases, yet the genetic contributions to variability in subclass traits are not fully understood. We conducted single-variant and gene-based association tests between 15.1M variants from genome-wide and exome array and imputed genotypes and 72 lipid and lipoprotein traits in 8,372 Finns. After accounting for 885 variants at 157 previously identified lipid loci, we identified five novel signals near established loci at HIF3A, ADAMTS3, PLTP, LCAT, and LIPG. Four of the signals were identified with a low-frequency (0.005<minor allele frequency [MAF]<0.05) or rare (MAF<0.005) variant, including Arg123His in LCAT. Gene-based associations (P<10−10) support a role for coding variants in LIPC and LIPG with lipoprotein subclass traits. 30 established lipid-associated loci had a stronger association for a subclass trait than any conventional trait. These novel association signals provide further insight into the molecular basis of dyslipidemia and the etiology of metabolic disorders

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Series: PLoS one
ISSN: 1932-6203
ISSN-E: 1932-6203
ISSN-L: 1932-6203
Volume: 13
Issue: 10
Article number: e1007079
DOI: 10.1371/journal.pgen.1007079
OADOI: https://oadoi.org/10.1371/journal.pgen.1007079
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
3142 Public health care science, environmental and occupational health
Subjects:
Funding: This study was supported by Academy of Finland (www.aka.fi) grants 77299 and 124243 (ML); the Finnish Heart Foundation (www.sydantutkimussaatio.fi/en/grants) (ML); the Finnish Diabetes Foundation (www.diabetestutkimus.fi/) (ML); and National Institutes of Health (https://grants.nih.gov/) grants R01DK093757 (KLM), R01DK072193 (KLM), U01DK105561 (KLM), U01DK062370 (MB), T32 HL129982 (JPD) and National Human Genome Research Institute Division of Intramural Research (www.genome.gov/10000004/grant-information/) project number Z01HG000024 (FSC). The serum NMR metabolomics platform has been supported by the Sigrid Juselius Foundation (sigridjuselius.fi) and the Strategic Research Funding from the University of Oulu (www.oulu.fi/university/node/35275). MAK works in a unit that is supported by the University of Bristol and UK Medical Research Council (www.mrc.ac.uk/) (MC_UU_1201/1). MAK has also been supported by Research Funding from the British Heart Foundation (www.bhf.org.uk/) and Wellcome Trust (wellcome.ac.uk/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Academy of Finland Grant Number: 77299
124243
Detailed Information: 77299 (Academy of Finland Funding decision)
124243 (Academy of Finland Funding decision)
Copyright information: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
  https://creativecommons.org/publicdomain/zero/1.0/