A genome-wide burden test for rare genetic variants.
Our understanding of the genetic mutations that affect complex human traits — such as height, smoking-related behaviour or the risk of diabetes — has been vastly broadened by genome-wide association studies .
But such research has focused largely on associations between traits of interest and variants that are common in the human population. Rare variants pose challenges to GWASs, because they can be studied using only large samples and in-depth genetic information, and can be more strongly confounded by non-genetic factors than can common variants, increasing the chance of spurious findings
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