Synthetic associations created by rare variants do not explain most GWAS results.

In a GWAS comprising of 3,322 cases and 3,587 controls [12] , the ISC analysis presented evidence that some common genetic variants also contribute to the genetic architecture, demonstrated by the highly significant signal of association of in an independent case-control sample based on a profile of the top 50% of associated SNPs from the ISC study.

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This is consistent with a slight trend towards the observed lower R 2 between composite value of the k causal variants and the common SNP allele for increasing k , implying a lower power of detection of synthetic associations with higher RAF.

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