Genome-wide association of echocardiographic dimensions, brachial artery endothelial function and treadmill exercise responses in the Framingham Heart Study

Vasan, Ramachandran S; Larson, Martin G; Aragam, Jayashri; Wang, Thomas J; Mitchell, Gary F; Kathiresan, Sekar; Newton-Cheh, Christopher; Vita, Joseph A; Keyes, Michelle J; O'Donnell, Christopher J; Levy, Daniel; Benjamin, Emelia J

doi:10.1186/1471-2350-8-S1-S2

Table 2 Top associations for Echo, ETT and BA function traits based on lowest p value for GEE test (2a), FBAT (2b), and Linkage (2c)*

From: Genome-wide association of echocardiographic dimensions, brachial artery endothelial function and treadmill exercise responses in the Framingham Heart Study

2A. Top Associations based on lowest GEE p values
Trait	SNP	Chromosome	Physical position	GEE p-value	FBAT p-value	In/near Gene (within 60 kb)
I. Top 15 SNPs associated with Echocardiographic Traits (Averaged across exams)
LV diastolic dimension	rs1379659	4	20296952	*1.1710** ^-7	0.001	SLIT2
LV fractional shortening	rs366676	6	88774485	*2.4410** ^-6	0.059	SPACA1
LV diastolic dimension	rs666088	4	20171404	*5.1010** ^-6	0.008	SLIT2
LV systolic dimension	rs10504543	8	73941196	*5.1810** ^-6	0.247	KCNB2
Left atrial diameter	rs1935881	1	186798043	*5.5610** ^-6	0.003	FAM5C
LV mass	rs10498091	2	221724949	*5.6810** ^-6	0.162
Left atrial diameter	rs10493389	1	66022886	*6.5610** ^-6	0.119	PDE4B
LV diastolic dimension	rs4920799	5	84642284	*6.8410** ^-6	0.041
LV wall thickness	rs10519181	15	76076030	*1.0410** ^-5	0.027	TBC1D2B
LV diastolic dimension	rs6104740	20	11284809	*1.1510** ^-5	0.021
LV diastolic dimension	rs2900208	12	11769731	*1.2010** ^-5	0.021	ETV6
LV systolic dimension	rs3766377	1	157613632	*1.2510** ^-5	0.032	CD244
LV diastolic dimension	rs10511762	9	25621130	*1.2910** ^-5	0.002	TUSC1
LV mass	rs4936770	11	122434085	*1.3710** ^-5	0.019	HSPA8
LV diastolic dimension	rs4485619	20	11251676	*1.5710** ^-5	0.043
II. Top 5 SNPs associated with ETT Traits
Stage 2 Exercise heart rate	rs6847149	4	111157701	*2.7410** ^-6	0.014	NOLA1
Stage 2 Exercise heart rate	rs2819770	1	234237045	*3.5310** ^-6	0.010	RYR2
Post-exercise 3 minute recovery SBP	rs746463	11	109501154	*4.8810** ^-6	0.564
Stage 2 Exercise heart rate	rs2056387	1	234250153	*5.1710** ^-6	0.002	RYR2
Stage 2 Exercise SBP	rs2553268	8	31055898	*6.3210** ^-6	0.001	WRN
III. Top 5 SNPs associated with BA endothelial function Traits
Baseline BA flow velocity	rs3814219	10	105637085	*9.4810** ^-7	0.325	OBFC1
BA FMD percent	rs4148686	7	116728468	*1.1310** ^-5	0.025	CFTR
Baseline BA flow velocity	rs1471639	14	33552277	*1.2610** ^-5	0.001
Baseline BA diameter	rs1045182	6	116705168	*1.4410** ^-5	0.058	TSPYL1
Baseline BA flow velocity	rs10515508	5	139355254	*1.7110** ^-5	0.016	NRG2
2B. Top associations based on lowest FBAT p value
Trait	SNP	Chromosome	Physical position	GEE p-value	FBAT p-value	In/near Gene (within 60 kb)
I. Top 15 SNPs associated with Echocardiographic Traits (Averaged across exams)
LV systolic dimension	rs1392284	3	114584100	0.139	*6.3910** ^-6	WDR52
LV fractional shortening	rs10515040	17	48859319	0.211	*1.2910** ^-5
LV fractional shortening	rs9312006	3	8234491	0.002	*1.6410** ^-5
LV systolic dimension	rs10504591	8	76199715	0.046	*1.9510** ^-5
LV fractional shortening	rs448458	15	60591780	0.206	*2.2610** ^-5
LV diastolic dimension	rs580859	13	68030441	0.046	*2.6810** ^-5
LV systolic dimension	rs1959290	14	86208482	2.07*10^-5	*6.4210** ^-5
Aortic root diameter	rs2468680	8	140590402	0.690	*6.1210** ^-5
LV systolic dimension	rs448458	15	60591780	0.019	*5.6010** ^-5
LV systolic dimension	rs2918268	5	148586949	0.574	*4.8210** ^-5	ABLIM3
LV mass	rs965036	6	20099022	0.033	*3.6910** ^-5
Left atrial diameter	rs1701821	7	112544622	0.137	*3.6610** ^-5
Aortic root diameter	rs7544568	1	38308301	0.194	*3.2110** ^-5
LV fractional shortening	rs10504591	8	76199715	0.112	*2.9210** ^-5
LV diastolic dimension	rs1488745	3	1976802	0.141	*2.7210** ^-5
II. Top 5 SNPs associated with ETT Traits
Post-exercise 3 minute recovery SBP	rs2016718	8	96813381	0.006	*2.2010** ^-7
Post-exercise 3 minute recovery heart rate	rs1029947	7	150713400	0.013	*9.2010** ^-7	PRKAG2
Post-exercise 3 minute recovery heart rate	rs1029946	7	150713454	0.022	*3.8910** ^-6	PRKAG2
Stage 2 Exercise heart rate	rs1958055	14	33254537	0.040	*8.5510** ^-6	NPAS3
Post-exercise 3 minute recovery SBP	rs7828552	8	71862761	0.057	*9.3410** ^-6	XRG9
III. Top 5 SNPs associated with BA endothelial function Traits
BA hyperemic flow velocity	rs1859634	7	100758808	0.030	*1.2110** ^-5	AK124120
BA FMD percent	rs1106494	14	62201734	0.003	*1.6110** ^-5	KCNH5
BA hyperemic flow velocity	rs2389866	4	120872866	0.423	*2.1210** ^-5	PDE5A
Baseline BA diameter	rs774227	9	91273496	0.002	*2.3410** ^-5	NFIL3
Baseline BA diameter	rs10502887	18	43433881	0.002	*2.7910** ^-5
2C. Magnitude and location of peak LOD scores ≥2.0 for Echo, ETT and BA function traits
Trait	SNP or STR	Chromosome	Physical position	Maximum LOD score	LOD-1.5 interval	LOD+1.5 interval
I. Echocardiographic Traits (Averaged across examinations)
LV mass	rs10515509	5	139270238	4.37	133816612	150634674
Aortic root diameter	rs10513442	3	154474088	4.22	150552924	161813142
LV wall thickness	rs3813713	10	51241137	3.16	32818116	58684005
LV wall thickness	rs10511550	9	10638555	3.11	10220368	15384347
LV fractional shortening	AFM254ve1	3	198506417	2.78	195278503	199138789
LV wall thickness	rs2438085	2	105339005	2.59	103478258	106924695
Left atrial diameter	rs7327514	13	78334100	2.55	68655834	90511230
LV wall thickness	rs1719	15	83149176	2.45	64238853	86738287
LV mass	rs10489725	1	181172198	2.41	176249023	201595809
LV mass	rs1989051	8	129363300	2.38	127811630	133926399
LV wall thickness	GATA164B08	3	8560016	2.25	2183832	20875136
II. ETT Traits
Stage 2 Exercise heart rate	rs190982	5	88259176	2.93	71236666	96112374
Stage 2 Exercise heart rate	GATA165C03	1	60383884	2.46	43070922	67006164
Stage 2 Exercise heart rate	rs7286558	22	20504737	2.43	15786453	25685518
Stage 2 Exercise heart rate	rs10483844	14	71902088	2.39	53240301	74937294
III. BA Endothelial Function Traits
Baseline BA flow velocity	rs1425727	8	25642697	2.14	19459783	32261074
BA FMD percent	D21S11	21	19476134	2.13	10000969	27037800
Baseline BA flow velocity	rs3007456	9	42925816	2.12	36878975	76736108

*SNPs are ordered by GEE p values. dbSNP positions are from NCBI Build 35 (hg17).
Abbreviations as in Table 1. The number of informative families for FBAT analyses ranged from a minimum of 80 to a maximum of 210.

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