Table 2. Set-unique burden of different variant types.

Variant Type	Disease status	Total genes	P value
Deleterious genes	Case	4,533	0.008
	Control	3,795
Splice site	Case	380	0.016
	Control	276
Stop-altering	Case	350	0.004
	Control	253
Double hits	Case	179	0.047
	Control	103

The polygenic burden of deleterious hits, splice site and stop-altering variants and double hits arising from set-unique SNVs (cases n=1,002, controls n=931). The category of double hits includes those genes for which an individual has two or more SNVs (of which at least one is predicted to be deleterious) within the borders of the gene. Each row contains the number of genes having at least one variant. Empirical P values for the difference in gene count are estimated empirically by permutation of phenotypes. Values in bold withstand correction for multiple testing (Supplementary Methods).