Coffee intake and risk of obesity, metabolic syndrome and type 2 diabetes: a Mendelian randomization study

TY - JOUR

T1 - Coffee intake and risk of obesity, metabolic syndrome and type 2 diabetes

T2 - a Mendelian randomization study

AU - Nordestgaard, Ask Tybjærg

AU - Thomsen, Mette

AU - Nordestgaard, Børge Grønne

N1 - © The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

PY - 2015/5/27

Y1 - 2015/5/27

N2 - Background: Coffee is one of the most widely consumed beverages. We tested the hypothesis that genetically high coffee intake is associated with low risk of obesity, metabolic syndrome and type 2 diabetes, and with related components thereof. Methods: We included 93 179 individuals from two large general population cohorts in a Mendelian randomization study. We tested first whether high coffee intake is associated with low risk of obesity, metabolic syndrome and type 2 diabetes, and with related components thereof, in observational analyses; second, whether five genetic variants near the CYP1A1, CYP1A2 and AHR genes are associated with coffee intake; and third, whether the genetic variants are associated with obesity, metabolic syndrome and type 2 diabetes, and with related components thereof. Finally, we tested the genetic association with type 2 diabetes in a meta-analysis including up to 78 021 additional individuals from the DIAGRAM consortium. Results: Observationally, high coffee intake was associated with low risk of obesity, metabolic syndrome and type 2 diabetes. Further, high coffee intake was associated with high body mass index, waist circumference, weight, height, systolic/diastolic blood pressure, triglycerides and total cholesterol and with low high-density lipoprotein cholesterol, but not with glucose levels. In genetic analyses, 9-10 vs 0-3 coffee-intake alleles were associated with 29% higher coffee intake. However, genetically derived high coffee intake was not associated convincingly with obesity, metabolic syndrome, type 2 diabetes, body mass index, waist circumference, weight, height, systolic/diastolic blood pressure, triglycerides, total cholesterol, high-density lipoprotein cholesterol or glucose levels. Perallele meta-analysed odds ratios for type 2 diabetes were 1.01 (0.98-1.04) for AHR rs4410790, 0.98 (0.95-1.01) for AHR rs6968865, 1.01 (0.99-1.03) for CYP1A1/2 rs2470893, 1.01 (0.98-1.03) for CYP1A1/2 rs2472297 and 0.98 (0.95-1.01) for CYP1A1 rs2472299. Conclusions: High coffee intake was associated observationally with low risk of obesity, metabolic syndrome and type 2 diabetes, and was associated observationally with related components thereof, but with no genetic evidence to support corresponding causal relationships.

AB - Background: Coffee is one of the most widely consumed beverages. We tested the hypothesis that genetically high coffee intake is associated with low risk of obesity, metabolic syndrome and type 2 diabetes, and with related components thereof. Methods: We included 93 179 individuals from two large general population cohorts in a Mendelian randomization study. We tested first whether high coffee intake is associated with low risk of obesity, metabolic syndrome and type 2 diabetes, and with related components thereof, in observational analyses; second, whether five genetic variants near the CYP1A1, CYP1A2 and AHR genes are associated with coffee intake; and third, whether the genetic variants are associated with obesity, metabolic syndrome and type 2 diabetes, and with related components thereof. Finally, we tested the genetic association with type 2 diabetes in a meta-analysis including up to 78 021 additional individuals from the DIAGRAM consortium. Results: Observationally, high coffee intake was associated with low risk of obesity, metabolic syndrome and type 2 diabetes. Further, high coffee intake was associated with high body mass index, waist circumference, weight, height, systolic/diastolic blood pressure, triglycerides and total cholesterol and with low high-density lipoprotein cholesterol, but not with glucose levels. In genetic analyses, 9-10 vs 0-3 coffee-intake alleles were associated with 29% higher coffee intake. However, genetically derived high coffee intake was not associated convincingly with obesity, metabolic syndrome, type 2 diabetes, body mass index, waist circumference, weight, height, systolic/diastolic blood pressure, triglycerides, total cholesterol, high-density lipoprotein cholesterol or glucose levels. Perallele meta-analysed odds ratios for type 2 diabetes were 1.01 (0.98-1.04) for AHR rs4410790, 0.98 (0.95-1.01) for AHR rs6968865, 1.01 (0.99-1.03) for CYP1A1/2 rs2470893, 1.01 (0.98-1.03) for CYP1A1/2 rs2472297 and 0.98 (0.95-1.01) for CYP1A1 rs2472299. Conclusions: High coffee intake was associated observationally with low risk of obesity, metabolic syndrome and type 2 diabetes, and was associated observationally with related components thereof, but with no genetic evidence to support corresponding causal relationships.

KW - Adult

KW - Aged

KW - Basic Helix-Loop-Helix Transcription Factors

KW - Blood Glucose

KW - Blood Pressure

KW - Body Mass Index

KW - Coffee

KW - Cytochrome P-450 CYP1A1

KW - Cytochrome P-450 CYP1A2

KW - Denmark

KW - Diabetes Mellitus, Type 2

KW - Female

KW - Humans

KW - Lipid Metabolism

KW - Male

KW - Mendelian Randomization Analysis

KW - Metabolic Syndrome X

KW - Middle Aged

KW - Obesity

KW - Polymorphism, Genetic

KW - Receptors, Aryl Hydrocarbon

KW - Risk Factors

U2 - 10.1093/ije/dyv083

DO - 10.1093/ije/dyv083

M3 - Journal article

C2 - 26002927

SN - 0300-5771

VL - 44

SP - 551

EP - 565

JO - International Journal of Epidemiology

JF - International Journal of Epidemiology

IS - 2

ER -