How should we use information about HWE in the meta-analyses of genetic association studies?
GROUND: It is often recommended that control groups in meta-analyses of genetic association studies are checked for Hardy-Weinberg equilibrium (HWE) as a surrogate for assessing study quality. However, tests for HWE have low power and there is currently no consensus about how to handle studies that deviate significantly from HWE. METHODS: We identified 72 papers describing 114 meta-analyses of 1603 primary gene-disease comparisons. Based on these studies and on related simulations, we evaluated four different strategies for handling studies that appear not to be in HWE: (i) include them in the meta-analysis; (ii) exclude them if the test for HWE results in P < 0.05; (iii) exclude them if a measure of the size of departure from HWE is large and (iv) exclude them if (ii) and (iii). RESULTS: Of the 72 papers, 26 did not report information on HWE, with a trend toward increased reporting with time. HWE was evaluated through testing, with only three papers assessing the size of departure. On
