Table 1.

SNPs (beta-coefficients and P-value) associated with plasma fibrinogen levels in the Women’s Genome Health Study (WGHS) after adjustment for age, smoking status, body mass index, menopausal status and current hormone replacement therapy

								Median Fibrinogen level (mg/dL)e			Genome-wide Association Values		Non-redundant SNPs at each Locus (from model selection)
Nearest Candidate Gene(s)	Loci	SNP	Positiona (bp)	Function	MAFb	HWc	A1-A2d	A1A1	A1A2	A2A2	Beta	P-valuef	Beta	P-valueg
IL6R	1q21.3	rs6684439	152662463	intron	0.40	0.36	G-A	353	350	345	-4.69	2.77×10-09
		rs4845623	152682401	intron	0.42	0.36	A-G	353	351	346	-4.55	6.08×10-09
		rs4537545	152685503	intron	0.41	0.20	G-A	353	351	345	-5.01	1.66×10-10
		rs4129267	152692888	intron	0.40	0.36	G-A	353	351	345	-5.30	1.84×10-11
		rs8192284h	152693594	coding-nonsynonymous	0.40	0.33	A-C	353	351	345	-5.30	1.80×10-11	-5.44	6.57×10-12
CPS1	2q34	rs7422339	211248752	coding-nonsynonymous	0.31	0.96	C-A	354	348	349	-4.84	8.82×10-09	-4.85	7.92×10-09
FGB, FGA, FGG	4q32.1	rs1388070	155520388	unknown	0.35	0.80	A-G	347	352	356	5.12	3.23×10-10
		rs4482740	155665755	unknown	0.36	0.43	G-A	346	352	360	6.32	4.40×10-15
		rs7654425	155676058	unknown	0.34	0.34	A-G	355	348	344	-5.19	2.98×10-10
		rs7698829	155680917	intron	0.14	1.00	A-G	352	348	339	-7.00	6.39×10-10
		rs1800790	155703158	locusi	0.21	0.04	G-A	345	358	370	12.31	2.91×10-38
		rs6056	155708271	coding-synonymous	0.18	0.16	G-A	346	359	370	12.94	8.04×10-39	14.08	2.45×10-42
		rs4220	155711209	coding-nonsynonymous	0.18	0.15	G-A	346	359	370	12.79	6.65×10-38
		rs1044291	155712802	unknown	0.34	0.56	G-A	355	348	344	-5.47	2.76×10-11
		rs2070016	155729764	intron	0.15	0.19	A-G	347	358	365	11.23	1.29×10-25
		rs1049636	155745420	intron	0.30	0.11	A-G	352	350	345	-5.19	9.95×10-10
		rs1800788	155703364	locus	0.20	0.46	G-A	350*	351*	350*	1.70	0.082*	5.13	3.68×10-07
SLC22A5, SLC22A4, IRF1	5q31.1	rs1016988	131772473	unknown	0.20	0.65	A-G	354	346	338	-6.84	1.24×10-12	-6.49	2.29×10-11
		rs10479002	131699561	coding-synonymous	0.04	1	G-C	350*	358*	383*	9.51	1.27×10-06*	8.36	2.33×10-05
CD300LF, SLC9A3R1, NAT9	17q25.1	rs10512597	70211428	intron	0.18	0.07	G-A	352	347	341	-6.45	7.72×10-11	-6.61	3.21×10-11
		rs1037170	70214509	intron	0.27	0.59	A-G	352	349	345	-5.22	2.29×10-09

Table 1 Legend

^*These 2 SNPs were identified in forward selection models that include the other lead SNPs in bold. See text for details.

^aBased on NCBI Build 36.1

^bMAF: Minor allele frequency based on the combined samples.

^cHW: Deviation from Hardy-Weinberg equilibrium P-value based on the combined samples.

^dA1=major allele, A2=minor allele. A1A1=homozygotes for major allele. A1A2=heterozygotes. A2A2=homozygotes for minor allele

^eCrude median fibrinogen levels (mg/dL) observed among homozygous carriers of the major allele, heterozygotes and homozygous carriers of the minor allele for each selected SNP

^fSNPs of genome-wide significance with P <5×10-08 are shown for residuals of fibrinogen regressed on each SNP.

^gP-values from forward selection models are shown, after adjustment for age, smoking habit, body mass index, menopausal status and current hormone therapy.

We evaluated for inclusion in this selection model 139 SNPs distributed across the 5 loci. P-values <0.00036 were considered to correct for the total number of SNPs considered.

^hIn bold are non-redundant SNPs in each of 5 loci that contribute to fibrinogen levels in forward selection model

ⁱWithin 2kb of a gene

Abbreviations

IL6R = interleukin 6 receptor

CPS1 = carbamoyl phosphate synthetase I

FGB = fibrinogen, beta polypeptide chain

FGA = fibrinogen, alpha polypeptide chain

FGG = fibrinogen, gamma polypeptide chain

SLC22A5 = solute carrier family 22 (organic cation transporter), member 5

SLC22A4 = solute carrier family 22 (organic cation transporter), member 4

IRF1= interferon regulatory factor 1

CD300LF = immunoglobulin superfamily, member 13;

SLC9A3R1=solute carrier family 9, isoform A3, regulatory factor 1;

NAT9= a member of the N-acetyltransferase family