DOI: 10.1101/472696Nov 19, 2018Paper

Evaluating causal associations between previously reported risk factors and epithelial ovarian cancer: a Mendelian randomization analysis

BioRxiv : the Preprint Server for Biology
James YarmolinskyRichard M Martin

Abstract

Background Various modifiable risk factors have been associated with epithelial ovarian cancer risk in observational epidemiological studies. However, the causal nature of the risk factors reported, and thus their suitability as effective intervention targets, is unclear given the susceptibility of conventional observational designs to residual confounding and reverse causation. Mendelian randomization uses genetic variants as proxies for modifiable risk factors to strengthen causal inference in observational studies. We used Mendelian randomization to evaluate the causal role of 13 previously reported risk factors (reproductive, anthropometric, clinical, lifestyle, and molecular factors) in overall and histotype-specific epithelial ovarian cancer in up to 25,509 case subjects and 40,941 controls in the Ovarian Cancer Association Consortium. Methods and Findings Genetic instruments to proxy 13 risk factors were constructed by identifying single nucleotide polymorphisms (SNPs) robustly ( P <5×10−8) and independently associated with each respective risk factor in previously reported genome-wide association studies. SNPs were combined into multi-allelic inverse-variance weighted fixed or random-effects models to generate causal e...Continue Reading

Related Concepts

Epidemiologic Studies
Diabetes Mellitus, Non-Insulin-Dependent
Endometriosis
Hormones
Menopause
Ovarian Carcinoma
Polycystic Ovary Syndrome
Regression Analysis
Research Subject
Adenocarcinoma, Clear Cell

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