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

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 a...

Celý popis

Uloženo v:

Podrobná bibliografie
Vydáno v:	PLoS genetics Ročník 13; číslo 10; s. e1007079
Hlavní autoři:	Davis, James P., Huyghe, Jeroen R., Locke, Adam E., Jackson, Anne U., Sim, Xueling, Stringham, Heather M., Teslovich, Tanya M., Welch, Ryan P., Fuchsberger, Christian, Narisu, Narisu, Chines, Peter S., Kangas, Antti J., Soininen, Pasi, Ala-Korpela, Mika, Kuusisto, Johanna, Collins, Francis S., Laakso, Markku, Boehnke, Michael, Mohlke, Karen L.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Public Library of Science 30.10.2017 Public Library of Science (PLoS)
Témata:	Biology and Life Sciences Cardiovascular disease Cardiovascular diseases Cholesterol, HDL - genetics Clinical medicine Consortia Diabetes Dyslipidemia Epidemiology Etiology Exome - genetics Finland Funding Gene frequency Gene Frequency - genetics Genetic aspects Genetic diversity Genetics Genome-Wide Association Study - methods Genomes Genotype Genotypes Health care Hospitals Humans Internal medicine Kinases Laboratories Lipid Metabolism - genetics Lipids Lipids - genetics Lipoproteins Lipoproteins - genetics Male Mens health Metabolic disorders Metabolism Middle Aged NMR Nuclear magnetic resonance Pharmacy Physiological aspects Polymorphism, Single Nucleotide - genetics Preventive medicine Principal Component Analysis - methods Software Studies Supervision Triglycerides Triglycerides - genetics White People - genetics Finland Ann Arbor Michigan United States > US
ISSN:	1553-7404, 1553-7390, 1553-7404
On-line přístup:	Získat plný text
Tagy:	Přidat tag Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!

Popis
Shrnutí:	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.
Bibliografie:	new_version ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 ML, MB, and KLM also contributed equally to this work. I have read the journal's policy and the authors of this manuscript have the following competing interests: AJK and PS are shareholders of Brainshake Ltd., a company offering NMR‑based metabolite profiling. AJK and PS report employment relation for Brainshake Ltd.
ISSN:	1553-7404 1553-7390 1553-7404
DOI:	10.1371/journal.pgen.1007079