Table 1.

Top associations between COVID-19 outcomes and protein-coding rare variants (p < 5E−8)

Gene	Varianta	Variant effect	Odds ratio (95% CI)	p value	N affected individuals with 0|1|2 copies of effect allele	N control individuals with 0|1|2 copies of effect allele	Effect allele frequency	Heterogeneity p value
COVID-19 positive versus COVID-19 negative or unknown
ZC3HAV1	rs769102632	missense	26.72 (8.37, 85.38)	2.95E−8	13,950|7|0	401,218|8|0	0.00002	0.9517
FLNB	rs1256764500	missense	26.6 (8.25, 85.77)	3.97E−8	18,616|7|0	500,616|8|0	0.00001	0.4354
COVID-19 positive versus COVID-19 negative
DISP3	burden	pLoF and deleterious missense with MAF < 10−3	1.88 (1.51, 2.34)	2.26E−8	20,727|145|0	74,172|301|0	0.00234	0.9972
COVID-19 hospitalized versus COVID-19 negative or unknown
WDR78	rs754119466	splice region	49.21 (13.61, 177.85)	2.81E−9	3,619|6|0	392,658|24|0	0.00004	1
TES	rs761377603	missense	38.91 (10.75, 140.9)	2.44E−8	4,555|5|0	511,328|23|0	0.00003	0.6601
MARK1	burden	pLoF variants with MAC = 1	40.19 (10.9, 148.1)	2.86E−8	4,473|5|0	530,595|34|0	0.00004	0.4035
SHC2	rs2287960	stop gained	42.94 (11.17, 165.02)	4.42E−8	4,237|5|0	483,826|17|0	0.00002	0.6742
COVID-19 severe versus COVID-19 negative or unknown
TLR7b	burden	pLoF and missense variants with MAF < 10−5	4.53 (2.64, 7.77)	4.28E−8	1,266|1|7	517,523|383|123	0.00062	0.7188

MAF, minor allele frequency; MAC, minor allele count; CI, confidence interval.

^aEffect allele for individual variants was rs769102632:A, rs1256764500:G, rs754119466:G, rs761377603:T, and rs2287960:T. For burden tests, individuals were considered to have 0 copies of the effect allele if they were homozygous for the reference allele for all variants included in the burden test, 1 copy of the effect allele if they were heterozygous for at least one variant, and 2 copies if they were homozygous for the alternate allele for at least one variant.

^bTLR7 is located on the X chromosome. Hemizygous males are included in the N of individuals with two copies of the effect allele.