Association between genetically determined leptin and blood lipids considering alcohol consumption: a Mendelian randomisation study

Objectives The objective of this study was to evaluate the association of genetically determined leptin with lipids.Design We conducted a Mendelian randomisation study to assess a potential causal relationship between serum leptin and lipid levels. We also evaluated whether alcohol drinking modified...

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Main Authors: Zhiyong Zou, Shengxu Li, Luqi Shen, José F Cordero, Jia-Sheng Wang, Ye Shen, Lirong Liang, Changwei Li
Format: Article
Language:English
Published: BMJ Publishing Group 2019-11-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/9/11/e026860.full
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author Zhiyong Zou
Shengxu Li
Luqi Shen
José F Cordero
Jia-Sheng Wang
Ye Shen
Lirong Liang
Changwei Li
author_facet Zhiyong Zou
Shengxu Li
Luqi Shen
José F Cordero
Jia-Sheng Wang
Ye Shen
Lirong Liang
Changwei Li
author_sort Zhiyong Zou
collection DOAJ
description Objectives The objective of this study was to evaluate the association of genetically determined leptin with lipids.Design We conducted a Mendelian randomisation study to assess a potential causal relationship between serum leptin and lipid levels. We also evaluated whether alcohol drinking modified the associations of genetically determined leptin with blood lipids.Setting and participants 3860 participants of the Framingham Heart Study third generation cohort.Results Both genetic risk scores (GRSs), the GRS generated using leptin loci independent of body mass index (BMI) and GRS generated using leptin loci dependent of BMI, were positively associated with log-transformed leptin (log-leptin). The BMI-independent leptin GRS was associated with log-transformed triglycerides (log-TG, β=−0.66, p=0.01), but not low-density lipoprotein cholesterol (LDL-C, p=0.99), high-density lipoprotein cholesterol (HDL-C, p=0.44) or total cholesterol (TC, p=0.49). Instrumental variable estimation showed that per unit increase in genetically determined log-leptin was associated with 0.55 (95% CI: 0.05 to 1.00) units decrease in log-TG. Besides significant association with log-TG (β=−0.59, p=0.009), the BMI-dependent GRS was nominally associated with HDL-C (β=−10.67, p=0.09) and TC (β=−28.05, p=0.08). When stratified by drinking status, the BMI-dependent GRS was associated with reduced levels of LDL-C (p=0.03), log-TG (p=0.004) and TC (p=0.003) among non-current drinkers only. Significant interactions between the BMI-dependent GRS and alcohol drinking were identified for LDL-C (p=0.03), log-TG (p=0.03) and TC (p=0.02).Conclusion These findings together indicated that genetically determined leptin was negatively associated with lipid levels and the association may be modified by alcohol consumption.
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spelling doaj-art-44b2192145e947fcbeab15d23c74b4932024-11-29T23:00:14ZengBMJ Publishing GroupBMJ Open2044-60552019-11-0191110.1136/bmjopen-2018-026860Association between genetically determined leptin and blood lipids considering alcohol consumption: a Mendelian randomisation studyZhiyong Zou0Shengxu Li1Luqi Shen2José F Cordero3Jia-Sheng Wang4Ye Shen5Lirong Liang6Changwei Li75 Institute of Child and Adolescent Health, Peking University School of Public Health, Beijing, China3 Children`s Minnesota Research Institute, Children`s Hospitals and Clinics of Minnesota, Minneapolis, Minnesota, USA1 Department of Epidemiology and Biostatistics, University of Georgia College of Public Health, Athens, Georgia, USA1 Department of Epidemiology and Biostatistics, University of Georgia College of Public Health, Athens, Georgia, USA2 Department of Environmental Health Science, University of Georgia College of Public Health, Athens, Georgia, USAOncology Research, Amgen Inc, South San Francisco, California, USADepartment of Clinical Epidemiology, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China1 Department of Epidemiology and Biostatistics, University of Georgia College of Public Health, Athens, Georgia, USAObjectives The objective of this study was to evaluate the association of genetically determined leptin with lipids.Design We conducted a Mendelian randomisation study to assess a potential causal relationship between serum leptin and lipid levels. We also evaluated whether alcohol drinking modified the associations of genetically determined leptin with blood lipids.Setting and participants 3860 participants of the Framingham Heart Study third generation cohort.Results Both genetic risk scores (GRSs), the GRS generated using leptin loci independent of body mass index (BMI) and GRS generated using leptin loci dependent of BMI, were positively associated with log-transformed leptin (log-leptin). The BMI-independent leptin GRS was associated with log-transformed triglycerides (log-TG, β=−0.66, p=0.01), but not low-density lipoprotein cholesterol (LDL-C, p=0.99), high-density lipoprotein cholesterol (HDL-C, p=0.44) or total cholesterol (TC, p=0.49). Instrumental variable estimation showed that per unit increase in genetically determined log-leptin was associated with 0.55 (95% CI: 0.05 to 1.00) units decrease in log-TG. Besides significant association with log-TG (β=−0.59, p=0.009), the BMI-dependent GRS was nominally associated with HDL-C (β=−10.67, p=0.09) and TC (β=−28.05, p=0.08). When stratified by drinking status, the BMI-dependent GRS was associated with reduced levels of LDL-C (p=0.03), log-TG (p=0.004) and TC (p=0.003) among non-current drinkers only. Significant interactions between the BMI-dependent GRS and alcohol drinking were identified for LDL-C (p=0.03), log-TG (p=0.03) and TC (p=0.02).Conclusion These findings together indicated that genetically determined leptin was negatively associated with lipid levels and the association may be modified by alcohol consumption.https://bmjopen.bmj.com/content/9/11/e026860.full
spellingShingle Zhiyong Zou
Shengxu Li
Luqi Shen
José F Cordero
Jia-Sheng Wang
Ye Shen
Lirong Liang
Changwei Li
Association between genetically determined leptin and blood lipids considering alcohol consumption: a Mendelian randomisation study
BMJ Open
title Association between genetically determined leptin and blood lipids considering alcohol consumption: a Mendelian randomisation study
title_full Association between genetically determined leptin and blood lipids considering alcohol consumption: a Mendelian randomisation study
title_fullStr Association between genetically determined leptin and blood lipids considering alcohol consumption: a Mendelian randomisation study
title_full_unstemmed Association between genetically determined leptin and blood lipids considering alcohol consumption: a Mendelian randomisation study
title_short Association between genetically determined leptin and blood lipids considering alcohol consumption: a Mendelian randomisation study
title_sort association between genetically determined leptin and blood lipids considering alcohol consumption a mendelian randomisation study
url https://bmjopen.bmj.com/content/9/11/e026860.full
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