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Causal effects of body mass index on cardiometabolic traits and events: a Mendelian randomization analysis

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Causal effects of body mass index on cardiometabolic traits and events : a Mendelian randomization analysis. / Holmes, Michael V.; Lange, Leslie A.; Palmer, Tom; Lanktree, Matthew B.; North, Kari E.; Almoguera, Berta; Buxbaum, Sarah; Chandrupatla, Hareesh R.; Elbers, Clara C.; Guo, Yiran; Hoogeveen, Ron C.; Li, Jin; Li, Yun R.; Swerdlow, Daniel I.; Cushman, Mary; Price, Tom S.; Curtis, Sean P.; Fornage, Myriam; Hakonarson, Hakon; Patel, Sanjay R.; Redline, Susan; Siscovick, David S.; Tsai, Michael Y.; Wilson, James G.; van der Schouw, Yvonne T.; FitzGerald, Garret A.; Hingorani, Aroon D.; Casas, Juan P.; de Bakker, Paul I. W.; Rich, Stephen S.; Schadt, Eric E.; Asselbergs, Folkert W.; Reiner, Alex P.; Keating, Brendan J.

In: American Journal of Human Genetics, Vol. 94, No. 2, 06.02.2014, p. 198-208.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Holmes, MV, Lange, LA, Palmer, T, Lanktree, MB, North, KE, Almoguera, B, Buxbaum, S, Chandrupatla, HR, Elbers, CC, Guo, Y, Hoogeveen, RC, Li, J, Li, YR, Swerdlow, DI, Cushman, M, Price, TS, Curtis, SP, Fornage, M, Hakonarson, H, Patel, SR, Redline, S, Siscovick, DS, Tsai, MY, Wilson, JG, van der Schouw, YT, FitzGerald, GA, Hingorani, AD, Casas, JP, de Bakker, PIW, Rich, SS, Schadt, EE, Asselbergs, FW, Reiner, AP & Keating, BJ 2014, 'Causal effects of body mass index on cardiometabolic traits and events: a Mendelian randomization analysis', American Journal of Human Genetics, vol. 94, no. 2, pp. 198-208. https://doi.org/10.1016/j.ajhg.2013.12.014

APA

Holmes, M. V., Lange, L. A., Palmer, T., Lanktree, M. B., North, K. E., Almoguera, B., Buxbaum, S., Chandrupatla, H. R., Elbers, C. C., Guo, Y., Hoogeveen, R. C., Li, J., Li, Y. R., Swerdlow, D. I., Cushman, M., Price, T. S., Curtis, S. P., Fornage, M., Hakonarson, H., ... Keating, B. J. (2014). Causal effects of body mass index on cardiometabolic traits and events: a Mendelian randomization analysis. American Journal of Human Genetics, 94(2), 198-208. https://doi.org/10.1016/j.ajhg.2013.12.014

Vancouver

Holmes MV, Lange LA, Palmer T, Lanktree MB, North KE, Almoguera B et al. Causal effects of body mass index on cardiometabolic traits and events: a Mendelian randomization analysis. American Journal of Human Genetics. 2014 Feb 6;94(2):198-208. https://doi.org/10.1016/j.ajhg.2013.12.014

Author

Holmes, Michael V. ; Lange, Leslie A. ; Palmer, Tom ; Lanktree, Matthew B. ; North, Kari E. ; Almoguera, Berta ; Buxbaum, Sarah ; Chandrupatla, Hareesh R. ; Elbers, Clara C. ; Guo, Yiran ; Hoogeveen, Ron C. ; Li, Jin ; Li, Yun R. ; Swerdlow, Daniel I. ; Cushman, Mary ; Price, Tom S. ; Curtis, Sean P. ; Fornage, Myriam ; Hakonarson, Hakon ; Patel, Sanjay R. ; Redline, Susan ; Siscovick, David S. ; Tsai, Michael Y. ; Wilson, James G. ; van der Schouw, Yvonne T. ; FitzGerald, Garret A. ; Hingorani, Aroon D. ; Casas, Juan P. ; de Bakker, Paul I. W. ; Rich, Stephen S. ; Schadt, Eric E. ; Asselbergs, Folkert W. ; Reiner, Alex P. ; Keating, Brendan J. / Causal effects of body mass index on cardiometabolic traits and events : a Mendelian randomization analysis. In: American Journal of Human Genetics. 2014 ; Vol. 94, No. 2. pp. 198-208.

Bibtex

@article{77a2b03be1ce41d1a47dc0d1f2054a2b,
title = "Causal effects of body mass index on cardiometabolic traits and events: a Mendelian randomization analysis",
abstract = "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.",
keywords = "Adolescent, Adult, Aged, Aged, 80 and over, Blood Glucose, Blood Pressure, Body Mass Index, Cholesterol, HDL, Cholesterol, LDL, Coronary Disease, Diabetes Mellitus, Type 2, European Continental Ancestry Group, Fasting, Female, Genetic Association Studies, Humans, Insulin, Interleukin-6, Longitudinal Studies, Male, Mendelian Randomization Analysis, Meta-Analysis as Topic, Middle Aged, Odds Ratio, Phenotype, Polymorphism, Single Nucleotide, Prospective Studies, Risk Factors, Selection, Genetic, Sensitivity and Specificity, Stroke, Young Adult",
author = "Holmes, {Michael V.} and Lange, {Leslie A.} and Tom Palmer and Lanktree, {Matthew B.} and North, {Kari E.} and Berta Almoguera and Sarah Buxbaum and Chandrupatla, {Hareesh R.} and Elbers, {Clara C.} and Yiran Guo and Hoogeveen, {Ron C.} and Jin Li and Li, {Yun R.} and Swerdlow, {Daniel I.} and Mary Cushman and Price, {Tom S.} and Curtis, {Sean P.} and Myriam Fornage and Hakon Hakonarson and Patel, {Sanjay R.} and Susan Redline and Siscovick, {David S.} and Tsai, {Michael Y.} and Wilson, {James G.} and {van der Schouw}, {Yvonne T.} and FitzGerald, {Garret A.} and Hingorani, {Aroon D.} and Casas, {Juan P.} and {de Bakker}, {Paul I. W.} and Rich, {Stephen S.} and Schadt, {Eric E.} and Asselbergs, {Folkert W.} and Reiner, {Alex P.} and Keating, {Brendan J.}",
note = "Copyright {\textcopyright} 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.",
year = "2014",
month = feb,
day = "6",
doi = "10.1016/j.ajhg.2013.12.014",
language = "English",
volume = "94",
pages = "198--208",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "2",

}

RIS

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 -