Sex and statin-related genetic associations at the PCSK9 gene locus: results of genome-wide association meta-analysis

Table 1 Overview of independent SNPs reaching at least suggestive significance in our GWAMA

	Cytoband	Independent SNP	EAF	Beta	p-value	Expl Var (%)	Best subgroup	Nearest/candidate gene (kb)
Known loci	1p32.3	rs11591147	0.015	− 0.372	1.70 × 10^–144	4.32	Free	PCSK9 (0)
		rs693668	0.633	0.052	7.80 × 10^–39	1.51	M	*PCSK9* (0)
		rs11583680	0.139	− 0.051	3.98 × 10^–20	0.76	M	*PCSK9* (0)
		rs2495491	0.756	− 0.039	5.01 × 10^–20	0.56	Free	*PCSK9* (6.8)
	2p24.1	rs1367117	0.314	− 0.029	2.09 × 10^–15	0.42	Free	*APOB* (3.3)
	10q21.3	rs10740131	0.481	0.018	1.44 × 10^–07	0.19	Free	*JMJD1C* (46)
	11q12.2	rs174535	0.331	0.022	1.49 × 10^–09	0.25	Free	*FADS1* (16)
	16q22.2	rs34042070	0.204	0.023	8.43 × 10^–08	0.19	Free	*HPR* (0), HP (6.6)
	19p13.11	rs8107974	0.087	− 0.040	5.76 × 10^–11	0.29	Free	TM6SF2 (4.3)
Novel loci	6q11.1	rs3076276	0.111	− 0.079	2.31 × 10^–08	1.22	Treated	KHDRBS2 (0)
	7q36.1	rs34924001	0.360	0.037	4.45 × 10^–07	0.51	M—free	PRKAG2 (0)
	10q11.21	rs76849715	0.050	0.058	6.52 × 10^–08	0.38	M—free	MARCHF8 (0), ALOX5 (140)
	12p12.2	rs4762806	0.058	− 0.077	3.44 × 10^–07	0.56	W—free	SLCO1B3 (0)
	12q24.22	rs4767549	0.405	− 0.022	1.41 × 10^–08	0.29	M	KSR2 (0), NOS1 (60)

For each locus, we report here the genomic cytoband, beta estimate, p-value and explained variance of the best-associated SNP in the best-associated subgroup. The loci are first ordered by novelty (first 6 loci: known, last 5 loci: novel), and then by chromosomal position via cytobands. For PCSK9 only, we report the four independent variants as detected by the conditional-joint analyses. Candidate genes are defined as nearest gene or other plausible gene as identified in literature review or co-localization analyses. The distance between lead SNP and candidate gene is given in kb. Bold written genes indicate positive co-localization of the PCSK9 signal and the expression of the candidate gene in at least one tissue (PP H4 ≥ 0.75). EAF: effect allele frequency; Free: statin-free subgroup (sex-combined); Treated: statin-treated subgroup (sex-combined); M: subgroup of men (statin-combined); M-Free: subgroup of statin-free men; W-Free: subgroup of statin-free women

ISSN: 2042-6410