Impact of sex hormone-binding globulin on the human phenome.

Human Molecular Genetics
Ryan ArathimosMatthew Suderman

Abstract

Sex hormone-binding globulin (SHBG) is a circulating glycoprotein and a regulator of sex hormone levels, which has been shown to influence various traits and diseases. The molecular nature of SHBG makes it a feasible target for preventative or therapeutic interventions. A systematic study of its effects across the human phenome may uncover novel associations. We used a Mendelian randomization phenome-wide association study (MR-pheWAS) approach to systematically appraise the potential functions of SHBG while reducing potential biases such as confounding and reverse causation common to the literature. We searched for potential causal effects of SHBG in UK Biobank (N = 334 977) and followed-up our top findings using two-sample MR analyses to evaluate whether estimates may be biased due to horizontal pleiotropy. Results of the MR-pheWAS across over 21 000 outcome phenotypes identified 12 phenotypes associated with genetically elevated SHBG after Bonferroni correction for multiple testing. Follow-up analysis using two-sample MR indicated the associations of increased natural log SHBG with higher impedance of the arms and whole body, lower pulse rate, lower bone density, higher odds of hip replacement, lower odds of high cholesterol ...Continue Reading

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Software Mentioned

PHESANT
PHEnome Scan ANalysis Tool ( PHESANT )
R
PRESSO
MR
- PRESSO Mendelian Randomization Pleiotropy
TwoSampleMR

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