Challenges in reproducibility of genetic association studies: lessons learned from the obesity field

International Journal of Obesity : Journal of the International Association for the Study of Obesity
A Li, D Meyre

Abstract

A robust replication of initial genetic association findings has proved to be difficult in human complex diseases and more specifically in the obesity field. An obvious cause of non-replication in genetic association studies is the initial report of a false positive result, which can be explained by a non-heritable phenotype, insufficient sample size, improper correction for multiple testing, population stratification, technical biases, insufficient quality control or inappropriate statistical analyses. Replication may, however, be challenging even when the original study describes a true positive association. The reasons include underpowered replication samples, gene × gene, gene × environment interactions, genetic and phenotypic heterogeneity and subjective interpretation of data. In this review, we address classic pitfalls in genetic association studies and provide guidelines for proper discovery and replication genetic association studies with a specific focus on obesity.

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Citations

Dec 27, 2013·BMC Genetics·Shannon SmithRomdhane Rekaya
Apr 12, 2013·Journal of Obesity·Shana McCormack, Struan F A Grant
Aug 7, 2013·International Journal of Obesity : Journal of the International Association for the Study of Obesity·C A HardmanM R Munafò
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May 16, 2019·Obesity Reviews : an Official Journal of the International Association for the Study of Obesity·Sahar EhteshamDavid Meyre
Nov 1, 2021·The Journal of Clinical Endocrinology and Metabolism·Darlène AntoineDavid Meyre

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