Genome-wide association analysis of metabolic syndrome quantitative traits in the GENNID multiethnic family study

Table 2 Significant MetS Quantitative Trait Association results (P ≤ 5 × 10^–8) by ethnic group

Ethnic group	Trait^a	rsid	CHR	BP (hg19)	A1	A2	A1 Freq in study^b	A1 Freq in AFR^c	A1 Freq in AMR^c	A1 Freq in EAS^c	A1 Freq in NFE^c
AA	log(TG)	rs75219957	1	231,296,755	G	C	0.020	0.012	0.133	0.278	0.0547
	log(TG)	rs568152609	4	31,060,113	C	T	0.010	0.007	0.002	0	0
	Glucose	rs138724790	5	86,997,218	C	T	0.010	0.016	0	0	0
	Glucose	rs78975723	6	39,338,990	G	C	0.010	0.033	0.002	0	6.5E−5
	log(TG)	rs73123056	7	63,354,705	A	C	0.040	0.024	0.073	0	0.048
	log(TG)	rs17137121	7	63,358,355	T	C	0.040	0.024	0.073	0	0.048
	log(TG)	rs114606502	12	130,117,352	C	T	0	0.007	0	0	0
	log(TG)	rs141776024	12	130,147,629	A	G	0	0.009	0	0	0
EA	log(TG)	rs1260326	2	27,730,940	T	C	0.400	0.135	0.314	0.501	0.400
	Weight	rs139940998	2	121,836,875	A	G	0.010	0.002	0.011	0	0.009
	Weight	rs144756634	2	121,843,978	A	T	0.010	0.002	0.011	0	0.009
	DBP	rs186742063^f	11	115,495,297	A	G	0.020	0.004	0.007	0	0.018
JA	Weight	rs2302308	4	122,258,149	G	T	0.012	0.025	0.062	0.071	0.106
	Weight	rs74398478	4	122,259,584	A	C	0.012	0.025	0.063	0.071	0.106
	Weight	rs17051338	4	122,260,042	G	T	0.012	0.025	0.063	0.073	0.106
	Weight	rs77438622	4	122,264,692	G	C	0.012	0.025	0.063	0.073	0.106
	Weight	rs77006299	4	122,270,900	C	A	0.012	0.025	0.063	0.073	0.106
	log(waist)	rs146792726	11	3,972,232	A	G	0.012	0	0	0.029	0
	log(waist)	rs147605117	11	4,063,916	G	C	0.012	0	0	0.031	0
	log(waist)	rs143126598	15	54,259,502	A	G	0.012	0.0002	0	0.009	0
MA	Glucose	rs17024841	4	149,556,752	A	G	0.030	0.010	0.020	0.144	0.051
	Glucose	rs111933650	4	149,558,682	T	C	0.030	0.010	0.020	0.144	0.050
	Glucose	rs76209611	4	149,561,328	G	T	0.040	0.011	0.020	0.145	0.057
	log(TG)	rs4522365	15	29,964,742	T	C	0.170	0.534	0.156	0.088	0.152

Ethnic group	Trait^a	rsid	Gene	Functional info	I^2d	Beta	SE	P
AA	log(TG)	rs75219957	FAM89A-TRIM67	Intergenic	80.4	1.04	0.19	3.0E−08
	log(TG)	rs568152609	PCDH7	Intronic	–	1.36	0.23	5.3E−09
	Glucose	rs138724790	CCNH-TMEM161B	Intergenic	–	1.93	0.35	3.7E−08
	Glucose	rs78975723	KIF6	Intronic	–	1.75	0.31	2.6E−08
	log(TG)	rs73123056	DQ599799-BC042811	Intergenic	84.5	0.81	0.15	2.4E−08
	log(TG)	rs17137121	DQ599799-BC042811	Intergenic	84.5	0.81	0.15	2.4E−08
	log(TG)	rs114606502	TMEM132D	Intronic	–	2.32	0.40	7.9E−09
	log(TG)	rs141776024	TMEM132D	Intronic	–	2.32	0.40	7.9E−09
EA	log(TG)	rs1260326	GCKR	Nonsyn	53.2	0.25	0.05	1.4E−07^e
	Weight	rs139940998	GLI2-TFCP2L1	Intergenic	–	1.84	0.32	7.3E−09
	Weight	rs144756634	GLI2-TFCP2L1	Intergenic	–	1.84	0.32	7.3E−09
	DBP	rs186742063^f	CADM1-LINC00900	Intergenic	90.9	1.42	0.26	4.4E−08
JA	Weight	rs2302308	QRFPR	Intronic	0	2.13	0.59	5.0E−08
	Weight	rs74398478	QRFPR	Intronic	0	2.13	0.59	5.0E−08
	Weight	rs17051338	QRFPR	Intronic	0	2.13	0.59	5.0E−08
	Weight	rs77438622	QRFPR	Intronic	0	2.13	0.59	5.0E−08
	Weight	rs77006299	QRFPR	Intronic	0	2.13	0.59	5.0E−08
	log(waist)	rs146792726	STIM1	Intronic	–	− 0.39	0.08	5.0E−08
	log(waist)	rs147605117	STIM1	Intronic	–	− 0.39	0.08	5.0E−08
	log(waist)	rs143126598	WDR72-UNC13C	Intergenic	–	− 0.39	0.08	5.0E−08
MA	Glucose	rs17024841	5S_rRNA-BC031092	Intergenic	80.6	− 0.70	0.12	1.7E−08
	Glucose	rs111933650	5S_rRNA-BC031092	Intergenic	80.6	− 0.70	0.12	1.7E−08
	Glucose	rs76209611	5S_rRNA-BC031092	Intergenic	78.9	− 0.67	0.12	4.2E−08
	log(TG)	rs4522365	FAM189A1-BC043570	Intergenic	74.8	− 0.29	0.05	2.0E−09

AA African Americans, EA European Americans, JA Japanese Americans, MA Mexican Americans
^aRank-based inverse normal transformation applied to weight, SBP (systolic blood pressure), DBP (diastolic blood pressure), and glucose traits
^bFrequency of A1 allele in GENNID as estimated by GCTA [45]
^cFrequency of A1 allele in gnomAD [76]: NFE (Non-Finnish Europeans) for EA, EAS (East Asians) for JA, AMR (Latinos) for MA, and AFR (African/African Americans) for AA
^dStatistic summarizing heterogeneity across ethnic groups; the percentage of variation of beta estimates across ethnic groups due to heterogeneity; values of 0 indicate no heterogeneity of effect sizes across ethnic groups; values over 75% and up to 100% indicate high levels of heterogeneity; missing values indicate the QTN was only analyzed in one ethnic group (either due to the QTN being monomorphic in the other ethnic groups or being filtered out during quality control in the other ethnic groups)
^ers1260326 nonsynonymous SNV was suggestive (5 × 10^–8 > P ≥ 10^–6) but was found to be significant in GENNID meta-analysis [40]
^frs186742063 has evidence of pleiotropy with suggestive evidence (P = 9.9E−08) of being associated with systolic blood pressure (SBP) (see Additional file 1: Table S1)

ISSN: 1758-5996