Table 2b.

Statistically significant associations at gene level for age at natural menopause.

Group	Gene	Chr.	SNP	Function	Position (bp)a	Major, Minor alleles	MAFb	Betac	s.e.	Raw p-valued	Adjusted p-valuee	Imputation quality (NHS/WGHS)	Other statistically significant SNPs in high linkage disequilibrium with the listed SNP (pairwise r2>0.8)
1	CYP19A1	15	rs11856927	Intronic	49335997	T,G	0.40	0.19	0.055	0.00051	0.023	0.93/0.93
	FSHB	11	rs621686	5′-UTR	30203352	G,A	0.076	0.32	0.10	0.0012	0.0071	1.00/1.00
			rs7951733	3′-UTR	30218544	G,A	0.082	−0.32	0.11	0.0026	0.016	0.87/0.73
			rs11031010	5′-UTR	30196754	C,A	0.15	0.21	0.076	0.0058	0.035	0.99/0.87
	LHCGR	2	rs1464729	3′-UTR	48817607	C,T	0.32	0.23	0.056	6.2E-05	0.0036	1.00/0.99
	PGR	11	rs619487	Intronic	100477546	G,T	0.34	0.19	0.056	0.00090	0.026	1.00/0.97	rs560291, rs596223, rs1145463, rs480851, rs485283, rs493957, rs493220, rs550778, rs506487
	SRD5A1	5	rs494958	Intronic	6692179	T,A	0.16	0.23	0.072	0.0014	0.037	1.00/1.00	rs1651074, rs535981
2	IGF1	12	rs1019731	Intronic	101366892	A,C	0.14	−0.28	0.076	0.00018	0.0053	1.00/1.00
	IGF2R	6	rs9457827	Intronic	160474067	C,T	0.064	0.37	0.11	0.00063	0.038	1.00/1.00
			rs2297362	Intronic	160469976	T,C	0.062	0.38	0.11	0.00068	0.041	0.99/1.00	rs1803989
3	SMAD7	18	rs4939833	Intronic	44721958	C,T	0.057	−0.40	0.12	0.0010	0.029	0.92/0.88	rs2337104, rs2337109
	TGFBR1	9	rs1590	3′-UTR	98995720	G,T	0.26	0.18	0.061	0.0026	0.042	0.99/0.97	rs334353, rs10819639, rs334348, rs7042852, rs334349
5	PCSK1	5	rs271924	Intronic	95763180	A,T	0.38	−0.18	0.055	0.0013	0.034	0.97/0.94
	PPARG	3	rs4135280	Intronic	12423994	C,T	0.037	0.54	0.14	0.00014	0.0048	0.84/1.00	rs2292101, rs12489347, rs4135283
	TNF	6	rs909253	5′-UTR	31648292	G,A	0.34	0.20	0.055	0.00022	0.0034	1.00/1.00	rs1041981
7	EIF2B4	2	rs7586601	3′-UTR	27496317	A,G	0.44	−0.19	0.055	0.00041	0.0020	0.95/0.92
			rs12476704	5′-UTR	27524682	C,A	0.38	−0.18	0.054	0.00093	0.0047	1.00/0.99	rs13472, rs7602534, rs2280737, rs7594812, rs1647284, rs1528533, rs6760828
	POLG	15	rs2351002	Intronic	87670333	G,C	0.40	−0.18	0.055	0.0013	0.019	0.98/0.96	rs12899409, rs2072266, rs758130, rs2302084, rs2307449, rs2246900, rs976072
8	NBN	8	rs2697679	Intronic	91019056	A,C	0.35	−0.24	0.055	1E-05	0.00021	1.00/0.97	rs2734823, rs1881469, rs2021881, rs2021882, rs9995, rs2142097, rs1063054, rs2735386, rs1063053, rs2735384, rs2735385, rs2735383
			rs2735387	Intronic	91020448	C,G	0.31	0.23	0.059	0.00013	0.0027	0.95/0.91	rs2735388, rs12680687
			rs7011299	5′-UTR	91082415	C,G	0.31	0.21	0.056	0.00020	0.0042	1.00/0.99	rs926092, rs2697677, rs1805794, rs2293775, rs1805833, rs16786, rs2097825, rs6985793, rs6470523, rs6470524, rs7840099, rs3736639
9	ANKK1	11	rs6279	3′-UTR	112786283	C,G	0.30	0.17	0.057	0.0032	0.044	0.99/0.98	rs2734842

^aPositions based on NCBI build 35;

^bMinor allele frequency among combined samples of the NHS and the WGHS;

^cThe regression parameter beta refers to the mean change in age at menarche or age at natural menopause per copy of the SNP minor allele;

^dThe unadjusted p-values are from linear regression with additive genetic coding;

^eThe p values are adjusted for multiple comparisons in each gene using the estimated effective number of independent markers. UTR, untranslated region.