title: Causal Role of Alcohol Consumption in an Improved Lipid Profile: The Atherosclerosis Risk in Communities (ARIC) Study.
abstract: BACKGROUND
  Health benefits of low-to-moderate alcohol consumption may operate through an improved lipid profile. A Mendelian randomization (MR) approach was used to examine whether alcohol consumption causally affects lipid levels.
  
  
  METHODS
  This analysis involved 10,893 European Americans (EA) from the Atherosclerosis Risk in Communities (ARIC) study. Common and rare variants in alcohol dehydrogenase and acetaldehyde dehydrogenase genes were evaluated for MR assumptions. Five variants, residing in the ADH1B, ADH1C, and ADH4 genes, were selected as genetic instruments and were combined into an unweighted genetic score. Triglycerides (TG), total cholesterol, high-density lipoprotein cholesterol (HDL-c) and its subfractions (HDL2-c and HDL3-c), low-density lipoprotein cholesterol (LDL-c), small dense LDL-c (sdLDL-c), apolipoprotein B (apoB), and lipoprotein (a) (Lp(a)) levels were analyzed.
  
  
  RESULTS
  Alcohol consumption significantly increased HDL2-c and reduced TG, total cholesterol, LDL-c, sdLDL-c, and apoB levels. For each of these lipids a non-linear trend was observed. Compared to the first quartile of alcohol consumption, the third quartile had a 12.3% lower level of TG (p < 0.001), a 7.71 mg/dL lower level of total cholesterol (p = 0.007), a 10.3% higher level of HDL2-c (p = 0.007), a 6.87 mg/dL lower level of LDL-c (p = 0.012), a 7.4% lower level of sdLDL-c (p = 0.037), and a 3.5% lower level of apoB (p = 0.058, poverall = 0.022).
  
  
  CONCLUSIONS
  This study supports the causal role of regular low-to-moderate alcohol consumption in increasing HDL2-c, reducing TG, total cholesterol, and LDL-c, and provides evidence for the novel finding that low-to-moderate consumption of alcohol reduces apoB and sdLDL-c levels among EA. However, given the nonlinearity of the effect of alcohol consumption, even within the range of low-to-moderate drinking, increased consumption does not always result in a larger benefit.
authors: School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas, United States of America.
authors: Khanh N
authors: KN
authors: Vu
authors: Section of Cardiovascular Research, Baylor College of Medicine, Houston, Texas, United States of America.|Houston Methodist Debakey Heart and Vascular Center, Houston, Texas, United States of America.
authors: Christie M
authors: CM
authors: Ballantyne
authors: Section of Cardiovascular Research, Baylor College of Medicine, Houston, Texas, United States of America.|Houston Methodist Debakey Heart and Vascular Center, Houston, Texas, United States of America.
authors: Ron C
authors: RC
authors: Hoogeveen
authors: Section of Cardiovascular Research, Baylor College of Medicine, Houston, Texas, United States of America.|Houston Methodist Debakey Heart and Vascular Center, Houston, Texas, United States of America.|Michael E DeBakey Veterans Affairs Hospital, Houston, Texas, United States of America.
authors: Vijay
authors: V
authors: Nambi
authors: Department of Biochemistry and Molecular Biology, University of Texas Medical School at Houston, Houston, Texas, United States of America.
authors: Kelly A
authors: KA
authors: Volcik
authors: School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas, United States of America.|The Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, United States of America.
authors: Eric
authors: E
authors: Boerwinkle
authors: School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas, United States of America.
authors: Alanna C
authors: AC
authors: Morrison
mesh_terms: D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000428:Alcohol Drinking / Q000097:blood / Q000235:genetics; D050197:Atherosclerosis / Q000097:blood / Q000235:genetics; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged
chemical_list: D008055:Lipids; C489332:ADH1B protein, human; C420272:ADH1C protein, human; D000426:Alcohol Dehydrogenase; C105552:alcohol dehydrogenase IV