Hardy-Weinberg equilibrium testing of biological ascertainment for Mendelian randomization studies.

American Journal of Epidemiology
Santiago RodriguezIan N M Day

Abstract

Mendelian randomization (MR) permits causal inference between exposures and a disease. It can be compared with randomized controlled trials. Whereas in a randomized controlled trial the randomization occurs at entry into the trial, in MR the randomization occurs during gamete formation and conception. Several factors, including time since conception and sampling variation, are relevant to the interpretation of an MR test. Particularly important is consideration of the "missingness" of genotypes that can be originated by chance, genotyping errors, or clinical ascertainment. Testing for Hardy-Weinberg equilibrium (HWE) is a genetic approach that permits evaluation of missingness. In this paper, the authors demonstrate evidence of nonconformity with HWE in real data. They also perform simulations to characterize the sensitivity of HWE tests to missingness. Unresolved missingness could lead to a false rejection of causality in an MR investigation of trait-disease association. These results indicate that large-scale studies, very high quality genotyping data, and detailed knowledge of the life-course genetics of the alleles/genotypes studied will largely mitigate this risk. The authors also present a Web program (http://www.oege.org...Continue Reading

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Citations

May 22, 2013·Blood Cells, Molecules & Diseases·Ching-Tien PengChien-Yu Lin
Nov 16, 2013·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·Dariusz KotlęgaSylwester Ciećwież
Dec 1, 2010·Animal : an International Journal of Animal Bioscience·A ZidiV M Fernández-Cabanás
May 11, 2012·Journal of Human Genetics·Min-Sheng PengYa-Ping Zhang
Jun 23, 2012·Laterality·Brian J PiperJeremy K Miller
Apr 23, 2011·DNA and Cell Biology·Walid Ben-SelmaJalel Boukadida
Sep 20, 2011·Annals of Oncology : Official Journal of the European Society for Medical Oncology·F CreaR Danesi
May 23, 2012·Annals of Human Genetics·Santiago RodriguezIan N M Day
Jun 15, 2012·Clinical and Vaccine Immunology : CVI·Walid Ben-Selma, Jalel Boukadida
Jul 21, 2012·Journal of Clinical Microbiology·Kok Siong PoonEvelyn Siew-Chuan Koay
Jan 8, 2011·Neuro-degenerative Diseases·Ming-Jen LeeMing-Jang Chiu
Mar 17, 2011·PloS One·Xianqiang LiuQifeng Yang
Aug 10, 2011·PloS One·Elena ShumayNora D Volkow
May 15, 2013·PloS One·Tom G RichardsonIan N M Day
Aug 23, 2012·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·Y D ApalasamyZ Mohamed

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Methods Mentioned

BETA
genotyping

Software Mentioned

SPSS
Stata
IC

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