Table 3.

Significant gene-centric and genetic region rare variant set analysis (after conditioning on known variants from the GWAS catalog and single-variant signals in the present analysis)

		Gene Centric Analysis
Trait	CHR	Symbol	category	# variants	cMAC	STAAR-O p-value
						unconditional	conditional	cond2round
C-Reactive Protein (CRP)	1	CRP	missense	54	336	3.6E-22	1.3E-08
Lipoprotein-associated phospholipase A2 (Lp-PLA2) Activity	6	PLA2G7	pLOF	5	14	1.3E-13	1.1E-13	1.6E-06
	6	PLA2G7	missense	56	323	6.4E-78	8.5E-28	3.9E-23
Lipoprotein-associated phospholipase A2 (Lp-PLA2) Mass	6	PLA2G7	pLOF	5	13	1.7E-10	1.1E-10
	6	PLA2G7	missense	55	326	1.8E-75	1.1E-18
Intercellular Adhesion Molecule 1 (ICAM-1)	19	ICAM1	missense	69	451	7.8E-15	5.0E-08	3.9E-05
	19	ZNF653	enhancer	126	577	2.3E-11	2.3E-11	8.7E-01
		Region-Based Analysis
Trait	CHR	pos_min	pos_max	# variants	cMAC	STAAR-O p-value
						unconditional	conditional	cond2round
Lipoprotein-associated phospholipase A2 (Lp-PLA2) Activity	6	46707812	46709811	103	526	2.2E-46	1.7E-20	9.1E-10
	6	46708812	46710811	95	389	6.9E-74	1.3E-21	4.2E-11
Lipoprotein-associated phospholipase A2 (Lp-PLA2) Mass	6	46707812	46709811	103	532	5.3E-44	9.3E-14
	6	46708812	46710811	94	394	1.3E-64	2.0E-14
Intercellular Adhesion Molecule 1 (ICAM-1)	19	11282547	11284546	68	591	6.1E-12	4.5E-10	6.8E-01
	19	11283547	11285546	91	892	7.7E-12	5.6E-10	9.7E-01
	19	11284547	11286546	96	1337	1.8E-09	7.0E-09	6.5E-01
	19	11285547	11287546	85	871	1.1E-09	1.8E-08	7.4E-01
	19	11503547	11505546	119	729	2.8E-11	2.8E-11	8.3E-01

Trait: trait name

CHR: chromosome where the gene is located

Symbol: gene symbols

Category: category of gene-based test; pLOF means putative loss of function

pos_min: starting position of the region tested, hg38

pos_max: ending position of the region tested, hg38

# variants: number of variants tested in the aggregate test

cMAC: cumulative minor allele count

STAAR-O p-value: p-values of aggregate tests in 3 cases

unconditional: p-value of unconditional analysis conditional: p-value of conditional analysis conditioning on (1) variants reported on previous literature (Table S8), (2) lead signals from our conditional single variant association analysis. cond2round: p-value of second round of conditional analysis: conditional list for second round conditional analysis consists of 2 parts: (1) conditional list for the first round conditional analysis; (2) additionally, variants included in the aggregate test which had nominally significant individual variant p-values (p<1.0×10⁻⁶) (Tables S10A and S11A). Note that not all gene sets have such remaining significant variants, so we do not further perform the second round conditional analysis in these cases, and leave the column blank.