DOI: 10.1101/19011536Nov 12, 2019Paper

Estimating the causal effect of adiposity on carpal tunnel syndrome: a Mendelian randomization study

MedRxiv : the Preprint Server for Health Sciences
Iyas Daghlas, N. Varady


Background: We aimed to examine evidence for a causal effect of overall and abdominal adiposity on carpal tunnel syndrome (CTS) using two-sample Mendelian randomization (MR). Methods: The exposure included genetic instruments comprising independent variants associated with body mass index (BMI) (n=322,154), a proxy for overall adiposity, and waist-hip ratio adjusted for BMI (WHRadjBMI) (n=210,082), a proxy for abdominal adiposity. Associations of these variants with CTS were obtained from a genome-wide association study (GWAS) conducted in UK Biobank (12,312 CTS cases / 389,344 controls). Causal effects were estimated using inverse-variance weighted regression and conventional MR sensitivity analyses were conducted to assess for horizontal pleiotropy. In follow-up analyses we determined whether type 2 diabetes (T2D) or hyperlipidemia mediated the observed effects. Results: A 1-standard deviation (SD, ~4.7kg/m2) increase in genetically instrumented BMI increased the risk of CTS (OR 1.73, 95% CI 1.48-2.02, p=2.68e-12), with consistent effects across sensitivity analyses. This effect translates to an absolute increase of 17 CTS cases per 1000 person years amongst US working populations [95% CI 11.0-23.5]. Univariable MR was consis...Continue Reading

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