Genetic architecture of lipid traits in the Hispanic community health study/study of Latinos

Graff, Mariaelisa; Emery, Leslie S.; Justice, Anne E.; Parra, Esteban; Below, Jennifer E.; Palmer, Nicholette D.; Gao, Chuan; Duan, Qing; Valladares-Salgado, Adan; Cruz, Miguel; Morrison, Alanna C.; Boerwinkle, Eric; Whitsel, Eric A.; Kooperberg, Charles; Reiner, Alex; Li, Yun; Rodriguez, Carlos Jose; Talavera, Gregory A.; Langefeld, Carl D.; Wagenknecht, Lynne E.; Norris, Jill M.; Taylor, Kent D.; Papanicolaou, George; Kenny, Eimear; Loos, Ruth J. F.; Chen, Yii-Der Ida; Laurie, Cathy; Sofer, Tamar; North, Kari E.

doi:10.1186/s12944-017-0591-6

Lipids in Health and Disease

Table 2 Replication and overall meta-analysis of 8 variants of interest with the indicated lipid trait

From: Genetic architecture of lipid traits in the Hispanic community health study/study of Latinos

Analysis or Study^a	rsID; Chr:Position; Effect/Other alleles ^b	Nearest Gene	Sample size	Effect allele frequency	Beta	Standard error	Pvalue^c	Meta-analysis generalization r-value^d
Trait = Total Cholesterol
Discovery study: HCHS/SOL	rs114378860; chr3:121,815,682; T/A	CD86	12,731	0.993	−17.930	3.091	6.62E-09	1.00
Replication meta-analysis, without HCHS/SOL			27,334	0.984	0.013	0.058	8.20E-01
Replication study: GUARDIAN-MACAD Mexican Americans			726	0.991	0.001	0.060	9.84E-01
Replication study: GUARDIAN-IRASFS Mexican Americans			1020	0.995	1.190	11.552	9.18E-01
Replication study: Mexican Ancestry Samples^e			3038	0.996	0.267	0.258	3.02E-01
Replication study: WHI Hispanic Americans			3361	0.996	10.724	10.374	3.01E-01
Replication study: ARIC African Americans			2488	0.966	−6.923	3.921	7.75E-02
Replication study: WHI African Americans			7943	0.962	0.114	2.077	9.56E-01
Replication study: ARIC European Americans			8758	0.999	−29.479	15.368	5.51E-02
Overall meta-analysis with HCHS/SOL			40,065	0.987	0.007	0.058	9.06E-01
Discovery study: HCHS/SOL	rs183336356; chr5:13,967,131; C/T	22 kb 5′ of DNAH5	12,731	0.998	−33.910	6.602	2.80E-07
Replication meta-analysis, without HCHS/SOL			13,792	0.991	−4.176	3.173	1.88E-01	0.63
Replication study: WHI Hispanic Americans			3361	0.999	−5.673	15.464	7.14E-01
Replication study: ARIC African Americans			2488	0.990	10.379	6.847	1.30E-01
Replication study: WHI African Americans			7943	0.989	−8.296	3.680	2.42E-02
Overall meta-analysis with HCHS/SOL			26,523	0.995	−9.755	2.860	6.47E-04
Trait = Triglycerides
Discovery study: HCHS/SOL	rs77635931; chr6:168,806,515: G/A	RP1-39 J2.1;SMOC2	12,730	0.998	−0.352	0.068	2.54E-07	1.00
Replication meta-analysis, without HCHS/SOL			35,236	0.993	0.039	0.027	1.47E-01
Replication study: GUARDIAN-HTN Mexican Americans			732	0.996	−0.046	0.132	7.26E-01
Replication study: Mexican Ancestry Samples			3047	0.998	0.284	0.355	4.24E-01
Replication study: WHI Hispanic Americans			3361	0.997	0.256	0.126	4.19E-02
Replication study: ARIC African Americans			2490	0.998	0.275	0.203	1.76E-01
Replication study: WHI African Americans			7943	0.998	−0.161	0.094	8.72E-02
Replication study: ARIC European Americans			8758	0.989	0.029	0.043	5.06E-01
Replication study: WHI European Americans			8905	0.989	0.061	0.041	1.38E-01
Overall meta-analysis with HCHS/SOL			47,966	0.995	−0.014	0.025	5.78E-01
Trait = HDL Cholesterol
Discovery study: HCHS/SOL	rs78768981; chr6:152,722,091; G/A	SYNE1	12,730	0.993	−5.522	0.962	9.29E-09	0.63
Replication meta-analysis, without HCHS/SOL			16,841	0.977	−0.296	0.250	2.35E-01
Replication study: Mexican Ancestry Samples			3047	0.998	−0.197	0.290	4.97E-01
Replication study: WHI Hispanic Americans			3361	0.996	5.007	2.504	4.55E-02
Replication study: ARIC African Americans			2490	0.954	−1.852	1.168	1.13E-01
Replication study: WHI African Americans			7943	0.954	−0.572	0.556	3.04E-01
Overall meta-analysis with HCHS/SOL			29,571	0.984	−0.626	0.242	9.59E-03
Discovery study: HCHS/SOL	rs77071750; chr7:6,579,655; C/G	DAGLB/GRID2IP	12,730	0.997	−7.975	1.498	1.01E-07
Replication meta-analysis, without HCHS/SOL			22,551	0.992	−2.466	0.952	9.58E-03	0.08
Replication study: WHI Hispanic Americans			3361	0.998	4.821	5.864	4.11E-01
Replication study: ARIC African Americans			2490	0.984	−2.364	2.221	2.87E-01
Replication study: WHI African Americans			7943	0.985	−2.598	1.081	1.62E-02
Replication study: ARIC European Americans			8757	1.000	−9.786	7.830	2.11E-01
Overall meta-analysis with HCHS/SOL			35,281	0.994	−4.050	0.803	4.62E-07
Discovery study: HCHS/SOL	rs191891263; chr7:69,496,422; A/G	AUTS2	12,730	0.998	−14.111	2.106	2.06E-11
Replication meta-analysis, without HCHS/SOL			15,074	0.984	0.083	0.415	8.41E-01	1.00
Replication study: Mexican Ancestry Samples			1281	0.998	0.016	0.483	9.73E-01
Replication study: WHI Hispanic Americans			3361	0.998	3.843	3.950	3.31E-01
Replication study: ARIC African Americans			2489	0.983	3.863	2.238	8.44E-02
Replication study: WHI African Americans			7943	0.977	−0.482	0.893	5.90E-01
Overall meta-analysis with HCHS/SOL			27,804	0.991	−0.448	0.407	2.72E-01
Discovery study: HCHS/SOL	rs184637772; chr11:116,702,251; T/C	APOC3	12,729	0.998	−7.698	1.637	2.57E-06
Replication meta-analysis, without HCHS/SOL			13,794	0.995	2.468	1.303	5.82E-02	1.00
Replication study: WHI Hispanic Americans			3361	0.999	5.805	5.925	3.27E-01
Replication study: ARIC African Americans			2490	0.993	4.410	3.143	1.61E-01
Replication study: WHI African Americans			7943	0.993	1.833	1.475	2.14E-01
Overall meta-analysis with HCHS/SOL			26,523	0.996	−1.474	1.019	1.48E-01
Trait = LDL Cholesterol
Discovery study: HCHS/SOL	rs149886784; chr14:74,138,147; C/T	DNAL1	12,467	0.998	−29.922	5.229	1.05E-08	0.66
Replication meta-analysis, without HCHS/SOL			14,782	0.989	−2.612	2.692	3.32E-01
Replication study: GUARDIAN-IRASFS Mexican Americans			1007	0.995	−1.584	10.112	8.76E-01
Replication study: WHI Hispanic Americans			3359	0.998	−3.031	11.855	7.98E-01
Replication study: ARIC African Americans			2474	0.988	−9.717	6.136	1.13E-01
Replication study: WHI African Americans			7942	0.985	−0.690	3.253	8.32E-01
Overall meta-analysis with HCHS/SOL			27,249	0.993	−8.334	2.394	4.98E-04

^a Replication studies included when the SNP was available and also met a minor allele count of ≥3. The results from the replication meta-analysis for each SNP is bolded
^b rsID according to dbSNP; Chromosome and Position are based on Human Genome Assembly 19
^c P-values are from unconditioned analyses
^d The directional FDR r-value for a SNP is the lowest directional FDR level at which we can say that it is generalized (replicated) with the same direction of association in both the discovery and generalizing studies. FDR r-values for generalization are based on one-side P-values with significance set at r-values <0.05
^e Mexican Ancestry samples come from the cohort of Starr County Mexican Americans and the Mexico City sample (Below et al. 2016) [9]

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