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

PLoS Genetics
James P DavisKaren L Mohlke

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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Citations

Jul 22, 2018·Cold Spring Harbor Molecular Case Studies·Julia WattacherilDavid B Goldstein
Oct 28, 2019·Critical Care Medicine·Tadanaga ShimadaKeith R Walley
Dec 6, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Rona J StrawbridgeDaniel J Smith
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Aug 18, 2021·Pharmacological Reports : PR·Carolina Dagli-HernandezRosario Dominguez Crespo Hirata

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Methods Mentioned

BETA
nuclear magnetic resonance
genotyping
NMR
exome sequencing
ChIP-seq
FAIRE-seq
exome-sequencing

Software Mentioned

R
PolyPhen
SIFT
Mutation Taster
Variant Effect Predictor ( VEP )
EPACTS
PolyPhen2
VEP
METSIM
HumDiv

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