Extended Data Table 3.

Comparison of the gene-based analysis including all coding variants or only variants predicted to be deleterious

	Benign + deleterious		Only deleterious
	p-value	OR (CI)	p-value	OR (CI)
All variants	1.44×10−11	2.75 (2.05-3.68)	2.52×10−12	2.86 (2.10-3.88)
Excluding V232M	1.58×10−8	2.58 (1.87-3.57)	2.95×10−8	2.54 (1.81-3.57)
Excluding A442 and V232M	1.61×10−3	2.86 (1.62-5.06)	5.88×10−5	3.20 (1.59-6.45)

Gene-based analyses were performed by SKAT-O. Variants that were predicted to be benign by both SIFT and Polyphen were removed for the second analysis