TY - JOUR
T1 - Novel insights into the consequences of obesity
T2 - a phenotype-wide Mendelian randomization study
AU - He, Chang
AU - Zhang, Miaoran
AU - Li, Jiuling
AU - Wang, Yiqing
AU - Chen, Lanlan
AU - Qi, Baiyu
AU - Wen, Jianping
AU - Yang, Jianli
AU - Lin, Sitong
AU - Liu, Dianyuan
AU - Dong, Ying
AU - Wang, Liying
AU - Wang, Qing
AU - Chen, Peng
N1 - © 2021. The Author(s), under exclusive licence to European Society of Human Genetics.
PY - 2022/5
Y1 - 2022/5
N2 - Obesity is thought to significantly impact the quality of life. In this study, we sought to evaluate the health consequences of obesity on the risk of a broad spectrum of human diseases. The causal effects of exposing to obesity on health outcomes were inferred using Mendelian randomization (MR) analyses using a fixed effects inverse-variance weighted model. The instrumental variables were SNPs associated with obesity as measured by body mass index (BMI) reported by GIANT consortium. The spectrum of outcome consisted of the phenotypes from published GWAS and the UK Biobank. The MR-Egger intercept test was applied to estimate horizontal pleiotropic effects, along with Cochran’s Q test to assess heterogeneity among the causal effects of instrumental variables. Our MR results confirmed many putative disease risks due to obesity, such as diabetes, dyslipidemia, sleep disorder, gout, smoking behaviors, arthritis, myocardial infarction, and diabetes-related eye disease. The novel findings indicated that elevated red blood cell count was inferred as a mediator of BMI-induced type 2 diabetes in our bidirectional MR analysis. Intriguingly, the effects that higher BMI could decrease the risk of both skin and prostate cancers, reduce calorie intake, and increase the portion size warrant further studies. Our results shed light on a novel mechanism of the disease-causing roles of obesity.
AB - Obesity is thought to significantly impact the quality of life. In this study, we sought to evaluate the health consequences of obesity on the risk of a broad spectrum of human diseases. The causal effects of exposing to obesity on health outcomes were inferred using Mendelian randomization (MR) analyses using a fixed effects inverse-variance weighted model. The instrumental variables were SNPs associated with obesity as measured by body mass index (BMI) reported by GIANT consortium. The spectrum of outcome consisted of the phenotypes from published GWAS and the UK Biobank. The MR-Egger intercept test was applied to estimate horizontal pleiotropic effects, along with Cochran’s Q test to assess heterogeneity among the causal effects of instrumental variables. Our MR results confirmed many putative disease risks due to obesity, such as diabetes, dyslipidemia, sleep disorder, gout, smoking behaviors, arthritis, myocardial infarction, and diabetes-related eye disease. The novel findings indicated that elevated red blood cell count was inferred as a mediator of BMI-induced type 2 diabetes in our bidirectional MR analysis. Intriguingly, the effects that higher BMI could decrease the risk of both skin and prostate cancers, reduce calorie intake, and increase the portion size warrant further studies. Our results shed light on a novel mechanism of the disease-causing roles of obesity.
KW - Genome-Wide Association Study
KW - Humans
KW - Mendelian Randomization Analysis
KW - Obesity/epidemiology
KW - Phenotype
KW - Polymorphism, Single Nucleotide
KW - Quality of Life
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U2 - 10.1038/s41431-021-00978-8
DO - 10.1038/s41431-021-00978-8
M3 - Article
C2 - 34974530
AN - SCOPUS:85122108506
SN - 1018-4813
VL - 30
SP - 540
EP - 546
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 5
ER -