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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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نویسنده
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davis j.p. ,huyghe j.r. ,locke a.e. ,jackson a.u. ,sim x. ,stringham h.m. ,teslovich t.m. ,welch r.p. ,fuchsberger c. ,narisu n. ,chines p.s. ,kangas a.j. ,soininen p. ,ala-korpela m. ,kuusisto j. ,collins f.s. ,laakso m. ,boehnke m. ,mohlke k.l.
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منبع
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plos genetics - 2017 - دوره : 13 - شماره : 10
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چکیده
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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. © 2017 public library of science. all rights reserved.
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آدرس
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department of genetics,university of north carolina at chapel hill,chapel hill,nc, United States, department of biostatistics and center for statistical genetics,university of michigan,ann arbor,mi, United States, department of biostatistics and center for statistical genetics,university of michigan,ann arbor,mi, United States, department of biostatistics and center for statistical genetics,university of michigan,ann arbor,mi, United States, department of biostatistics and center for statistical genetics,university of michigan,ann arbor,mi, United States, department of biostatistics and center for statistical genetics,university of michigan,ann arbor,mi, United States, department of biostatistics and center for statistical genetics,university of michigan,ann arbor,mi, United States, department of biostatistics and center for statistical genetics,university of michigan,ann arbor,mi, United States, department of biostatistics and center for statistical genetics,university of michigan,ann arbor,mi, United States, national human genome research institute,national institutes of health,bethesda,md, United States, national human genome research institute,national institutes of health,bethesda,md, United States, computational medicine,faculty of medicine,university of oulu and biocenter oulu,oulu, Finland, computational medicine,faculty of medicine,university of oulu and biocenter oulu,oulu,finland,nmr metabolomics laboratory,school of pharmacy,university of eastern finland,kuopio, Finland, computational medicine,faculty of medicine,university of oulu and biocenter oulu,oulu,finland,nmr metabolomics laboratory,school of pharmacy,university of eastern finland,kuopio,finland,population health science,bristol medical school,university of bristol and medical research council integrative epidemiology unit at the university of bristol,bristol,united kingdom,systems epidemiology,baker heart and diabetes institute,melbourne,vic,australia,department of epidemiology and preventive medicine,school of public health and preventive medicine,faculty of medicine nursing and health sciences,the alfred hospital,monash university,melbourne,vic, Australia, institute of clinical medicine,internal medicine,university of eastern finland and kuopio university hospital,kuopio, Finland, national human genome research institute,national institutes of health,bethesda,md, United States, institute of clinical medicine,internal medicine,university of eastern finland and kuopio university hospital,kuopio, Finland, department of biostatistics and center for statistical genetics,university of michigan,ann arbor,mi, United States, department of genetics,university of north carolina at chapel hill,chapel hill,nc, United States
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Authors
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