Final published version
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
TY - JOUR
T1 - Causal effects of body mass index on cardiometabolic traits and events
T2 - a Mendelian randomization analysis
AU - Holmes, Michael V.
AU - Lange, Leslie A.
AU - Palmer, Tom
AU - Lanktree, Matthew B.
AU - North, Kari E.
AU - Almoguera, Berta
AU - Buxbaum, Sarah
AU - Chandrupatla, Hareesh R.
AU - Elbers, Clara C.
AU - Guo, Yiran
AU - Hoogeveen, Ron C.
AU - Li, Jin
AU - Li, Yun R.
AU - Swerdlow, Daniel I.
AU - Cushman, Mary
AU - Price, Tom S.
AU - Curtis, Sean P.
AU - Fornage, Myriam
AU - Hakonarson, Hakon
AU - Patel, Sanjay R.
AU - Redline, Susan
AU - Siscovick, David S.
AU - Tsai, Michael Y.
AU - Wilson, James G.
AU - van der Schouw, Yvonne T.
AU - FitzGerald, Garret A.
AU - Hingorani, Aroon D.
AU - Casas, Juan P.
AU - de Bakker, Paul I. W.
AU - Rich, Stephen S.
AU - Schadt, Eric E.
AU - Asselbergs, Folkert W.
AU - Reiner, Alex P.
AU - Keating, Brendan J.
N1 - Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
PY - 2014/2/6
Y1 - 2014/2/6
N2 - Elevated body mass index (BMI) associates with cardiometabolic traits on observational analysis, yet the underlying causal relationships remain unclear. We conducted Mendelian randomization analyses by using a genetic score (GS) comprising 14 BMI-associated SNPs from a recent discovery analysis to investigate the causal role of BMI in cardiometabolic traits and events. We used eight population-based cohorts, including 34,538 European-descent individuals (4,407 type 2 diabetes (T2D), 6,073 coronary heart disease (CHD), and 3,813 stroke cases). A 1 kg/m(2) genetically elevated BMI increased fasting glucose (0.18 mmol/l; 95% confidence interval (CI) = 0.12-0.24), fasting insulin (8.5%; 95% CI = 5.9-11.1), interleukin-6 (7.0%; 95% CI = 4.0-10.1), and systolic blood pressure (0.70 mmHg; 95% CI = 0.24-1.16) and reduced high-density lipoprotein cholesterol (-0.02 mmol/l; 95% CI = -0.03 to -0.01) and low-density lipoprotein cholesterol (LDL-C; -0.04 mmol/l; 95% CI = -0.07 to -0.01). Observational and causal estimates were directionally concordant, except for LDL-C. A 1 kg/m(2) genetically elevated BMI increased the odds of T2D (odds ratio [OR] = 1.27; 95% CI = 1.18-1.36) but did not alter risk of CHD (OR 1.01; 95% CI = 0.94-1.08) or stroke (OR = 1.03; 95% CI = 0.95-1.12). A meta-analysis incorporating published studies reporting 27,465 CHD events in 219,423 individuals yielded a pooled OR of 1.04 (95% CI = 0.97-1.12) per 1 kg/m(2) increase in BMI. In conclusion, we identified causal effects of BMI on several cardiometabolic traits; however, whether BMI causally impacts CHD risk requires further evidence.
AB - Elevated body mass index (BMI) associates with cardiometabolic traits on observational analysis, yet the underlying causal relationships remain unclear. We conducted Mendelian randomization analyses by using a genetic score (GS) comprising 14 BMI-associated SNPs from a recent discovery analysis to investigate the causal role of BMI in cardiometabolic traits and events. We used eight population-based cohorts, including 34,538 European-descent individuals (4,407 type 2 diabetes (T2D), 6,073 coronary heart disease (CHD), and 3,813 stroke cases). A 1 kg/m(2) genetically elevated BMI increased fasting glucose (0.18 mmol/l; 95% confidence interval (CI) = 0.12-0.24), fasting insulin (8.5%; 95% CI = 5.9-11.1), interleukin-6 (7.0%; 95% CI = 4.0-10.1), and systolic blood pressure (0.70 mmHg; 95% CI = 0.24-1.16) and reduced high-density lipoprotein cholesterol (-0.02 mmol/l; 95% CI = -0.03 to -0.01) and low-density lipoprotein cholesterol (LDL-C; -0.04 mmol/l; 95% CI = -0.07 to -0.01). Observational and causal estimates were directionally concordant, except for LDL-C. A 1 kg/m(2) genetically elevated BMI increased the odds of T2D (odds ratio [OR] = 1.27; 95% CI = 1.18-1.36) but did not alter risk of CHD (OR 1.01; 95% CI = 0.94-1.08) or stroke (OR = 1.03; 95% CI = 0.95-1.12). A meta-analysis incorporating published studies reporting 27,465 CHD events in 219,423 individuals yielded a pooled OR of 1.04 (95% CI = 0.97-1.12) per 1 kg/m(2) increase in BMI. In conclusion, we identified causal effects of BMI on several cardiometabolic traits; however, whether BMI causally impacts CHD risk requires further evidence.
KW - Adolescent
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Blood Glucose
KW - Blood Pressure
KW - Body Mass Index
KW - Cholesterol, HDL
KW - Cholesterol, LDL
KW - Coronary Disease
KW - Diabetes Mellitus, Type 2
KW - European Continental Ancestry Group
KW - Fasting
KW - Female
KW - Genetic Association Studies
KW - Humans
KW - Insulin
KW - Interleukin-6
KW - Longitudinal Studies
KW - Male
KW - Mendelian Randomization Analysis
KW - Meta-Analysis as Topic
KW - Middle Aged
KW - Odds Ratio
KW - Phenotype
KW - Polymorphism, Single Nucleotide
KW - Prospective Studies
KW - Risk Factors
KW - Selection, Genetic
KW - Sensitivity and Specificity
KW - Stroke
KW - Young Adult
U2 - 10.1016/j.ajhg.2013.12.014
DO - 10.1016/j.ajhg.2013.12.014
M3 - Journal article
C2 - 24462370
VL - 94
SP - 198
EP - 208
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 2
ER -