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[Evaluating the causal relationship between hip circumference and coronary heart disease: a Mendelian randomization

Tonghui Yuan¹, Hongkai Li¹, Yuntao Ma¹

¹Institute for Medical Dataology, Chelloo College of Medicine, Shandong University, Department of Biostatistics, School of Public Health, Chelloo College of Medicine, Shandong University, Jinan 250012, China.

Wei Sheng Yan Jiu = Journal of Hygiene Research

|July 23, 2020

Abstract

Objective:

To test the causal effect of hip circumference adjusted for body mass index(HCadjBMI) and coronary heart disease(CHD) using a Mendelian randomization analysis.

Methods:

Based on genome-wide association study, the associations between the genetic instruments(IVs) and HCadjBMI were obtained from the GIANT consortium(n=211 114, European), the associations between IVs and CHD were derided from CARDIoGRAM consortium(n=86 995, European). The inverse-variance weighted method was used to estimate a pooled OR for the effect of a 1 cm higher HCadjBMI on CHD. Evidence of directional pleiotropy averaged across all variants was sought using MR-Egger regression.

Results:

A total of 70 genetic variants that reached genome-wide significance and independent of each other were identified as IVs. A combined genetic variants expected to confer a lifetime exposure of per SD higher HCadjBMI was associated with a lower risk of CHD(OR=0. 831, 95%CI 0. 730-0. 946). MR-Egger regression intercept suggested that directional pleiotropy was unlikely to be biasing the result(intercept-0. 0012, P=0. 875). There was no specific single nucleotide polymorphism(SNP) detected by "leave one out" analysis.

Conclusion:

A genetic predisposition to higher HCadjBMI was associated with lower risk of CHD.

Keywords:

Mendelian randomization analysis causal inference coronary heart disease epidemiology hip circumference

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