Table 3.

Gene-Burden Associations of Candidate Effector Genes from European GWASs for Body Mass Index, Type 2 Diabetes, and Plasma Lipid Levels in the SWAI Study

Sentinel Variant	Associations from European GWASs						Gene-Burden Associations in the SWAI Study
	Closest Gene	Variant Effect	AAF	Trait	Effecta	p Value	Gene	Top Maskb	Freq	Effecta	p Value
BMI46
rs6567160	MC4R	intergenic	0.23	BMIc	0.06	1.8E−178	MC4R	M3.1	0.011	0.56	5.2E−09
Type 2 Diabetes47
rs523288	MC4R	intergenic	0.24	T2D	1.05	7.6E−13	MC4R	M3.1	0.010	2.62	1.2E−05
rs67254669	ABCC8	missense	0.001	T2D	1.89	1.1E−08	ABCC8	M3.5	0.018	2.21	9.3E−06
Plasma Lipid Levels48
rs541041	APOB	intergenic	0.81	TC	0.11	5.3E−237	APOB	M4.5	0.062	−0.21	1.4E−06
				LDLC	0.12	1.3E−287				−0.29	1.6E−09
rs445925	APOE	downstream	0.11	TC	−0.21	0	APOE	M4.1	0.014	−0.63	9.4E−14
				LDLC	−0.32	0				−0.86	4.7E−20
rs11591147	PCSK9	missense	0.015	TC	−0.41	0	PCSK9	M2.5	0.057	−0.20	6.2E−06
				LDLC	−0.48	0		M3.5	0.028	−0.44	9.1E−11
rs58542926	TM6SF2	missense	0.07	TC	−0.13	7.0E−155	TM6SF2	M4.5	0.067	−0.26	4.6E−10
				LDLC	−0.10	6.5E−93				−0.22	7.9E−07
				TG	−0.12	3.7E−125				−0.28	2.5E−11
rs2792751	GPAM	missense	0.73	HDLC	−0.03	3.8E−21	GPAM	M3.5	0.026	0.58	5.1E−15
rs1800588	LIPC	upstream	0.24	HDLC	0.12	0	LIPC	M4.1	0.013	0.47	9.8E−6
rs622082	IGHMBP2	missense	0.31	HDLC	−0.02	5.90E−10	CPT1A	M2.1	0.014	−0.50	1.30E−06
rs12328675	COBLL1	3′ UTR	0.12	HDLC	0.05	3.1E−37	GRB14	M2.1	0.013	−0.46	1.8E−05
rs964184	ZPR1	3′ UTR	0.85	TC	−0.09	4.7E−135	APOC3	M4.5	0.026	−0.35	3.1E−08
				HDLC	0.11	2.6E−217				0.74	6.0E−23
				TG	−0.25	0				−1.16	7.5E−72

Abbreviations are as follows: AAF, alternate allele frequency; BMI, body mass index; T2D, type 2 diabetes; TC, total cholesterol; LDLC, low-density lipoprotein cholesterol; HDLC, high-density lipoprotein cholesterol; TG, triglyceride.

^aThe effects are beta coefficients in the standard deviation unit of normalized traits for BMI and lipid traits and odds ratios for T2D.

^bThe mask with strongest trait association is displayed. Refer to Subjects and Methods for a detailed mask definition.

^cBMI in the SWAI study is maximum BMI.