Combined Association of Body Mass Index and Alcohol Consumption With Biomarkers for Liver Injury and Incidence of Liver Disease

Key Points Question Is there a joint association of body mass index and alcohol consumption with liver disease and liver injury biomarkers? Findings In this mendelian randomization study of a population-based cohort of 91 552 European adults, compared with individuals categorized as having both a high body mass index and weekly units of alcohol consumption, those in the low category for both of these risk factors were associated with lower circulating liver injury biomarkers compared with being high for either one or both of the risk factors. However, this association was less clear when considering cases of liver disease as the outcome. Meaning Interventions to reduce both body mass index and alcohol consumption may result in the greatest reduction in circulating liver injury biomarkers, but these results do not appear to be able to demonstrate whether these interventions will result in a reduction in cases of liver disease.

[1]  N. Sheehan,et al.  Correcting the Standard Errors of 2-Stage Residual Inclusion Estimators for Mendelian Randomization Studies , 2017, American journal of epidemiology.

[2]  Debbie A Lawlor,et al.  Triangulation in aetiological epidemiology , 2016, International journal of epidemiology.

[3]  G. Davey Smith,et al.  Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator , 2016, Genetic epidemiology.

[4]  R. Brook,et al.  Effect of naturally random allocation to lower low-density lipoprotein cholesterol on the risk of coronary heart disease mediated by polymorphisms in NPC1L1, HMGCR, or both: a 2 × 2 factorial Mendelian randomization study. , 2015, Journal of the American College of Cardiology.

[5]  G. Davey Smith,et al.  Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression , 2015, International journal of epidemiology.

[6]  Ross M. Fraser,et al.  Genetic studies of body mass index yield new insights for obesity biology , 2015, Nature.

[7]  D. Lawlor,et al.  ADH1B and ADH1C Genotype, Alcohol Consumption and Biomarkers of Liver Function: Findings from a Mendelian Randomization Study in 58,313 European Origin Danes , 2014, PloS one.

[8]  G. Davey Smith,et al.  Mendelian randomization: genetic anchors for causal inference in epidemiological studies , 2014, Human molecular genetics.

[9]  L. Kaplan,et al.  Obesity and liver disease: the epidemic of the twenty-first century. , 2014, Clinics in liver disease.

[10]  D. Lawlor,et al.  Exploring causal associations between alcohol and coronary heart disease risk factors: findings from a Mendelian randomization study in the Copenhagen General Population Study. , 2013, European heart journal.

[11]  S. Thompson,et al.  Avoiding bias from weak instruments in Mendelian randomization studies. , 2011, International journal of epidemiology.

[12]  V. Beral,et al.  Body mass index and risk of liver cirrhosis in middle aged UK women: prospective study , 2010, BMJ : British Medical Journal.

[13]  G. Davey Smith,et al.  Supplementary Tables , 2009 .

[14]  B. Nordestgaard,et al.  Alcohol Intake, Alcohol Dehydrogenase Genotypes, and Liver Damage and Disease in the Danish General Population , 2009, The American Journal of Gastroenterology.

[15]  S. Bellentani,et al.  Epidemiology and natural history of non-alcoholic fatty liver disease (NAFLD). , 2009, Annals of hepatology.

[16]  R. Bloigu,et al.  Effect of moderate alcohol consumption on liver enzymes increases with increasing body mass index. , 2008, The American journal of clinical nutrition.

[17]  George Davey Smith,et al.  Mendelian randomization: Using genes as instruments for making causal inferences in epidemiology , 2008, Statistics in medicine.

[18]  D. Lawlor,et al.  Clustered Environments and Randomized Genes: A Fundamental Distinction between Conventional and Genetic Epidemiology , 2007, PLoS medicine.

[19]  Eva Negri,et al.  Worldwide mortality from cirrhosis: an update to 2002. , 2007, Journal of hepatology.

[20]  R. Bloigu,et al.  Additive effects of moderate drinking and obesity on serum γ-glutamyl transferase activity , 2006 .

[21]  A. Diehl.  Obesity and alcoholic liver disease. , 2004, Alcohol.

[22]  S. Ebrahim,et al.  'Mendelian randomization': can genetic epidemiology contribute to understanding environmental determinants of disease? , 2003, International journal of epidemiology.

[23]  Mario Cleves,et al.  Hardy-Weinberg equilibrium test and allele frequency estimation , 1999 .