Table 3.

Summary of pathway/group results for age at menarche and age at natural menopause.

Group	Biological Pathway or Related-phenotype	Number of Genes	Number of SNPs	Unadjusted p-value of Most Significant SNP (Associated Gene)	Observed Number of Significant Genesa	Expected Number of Significant Genesb	Observed: Expected	p-value for Groupc
Age at Menarche
1	Steroid-hormone metabolism and biosynthesis	38	2,627	0.00010 (LHCGR)	4	1.9	2.1	0.040
2	IGF pathway	24	1,547	0.0032 (GHRH)	1	1.2	0.8	0.34
3	TGF-β superfamily and signaling pathway	49	2,878	0.0022 (INHA)	0	2.5	0.0	0.92
4	Thrombophilia and vascular homeostasis	32	2,069	0.00098(AGT)	1	1.6	0.6	0.48
5	Obesity and obesity-related phenotypes	36	2,437	0.00043 (FTO)	0	1.8	0.0	0.84
6	Precocious or delayed puberty	19	1,343	0.00074 (BCAT1)	3	1.0	3.2	0.013
Total		198	12,901	0.00010 (LHCGR)	9	9.9	0.9	0.53
Age at Natural Menopause
1	Steroid-hormone metabolism and biosynthesis	38	2,627	6.2E-05(LHCGR)	5	1.9	2.6	0.011
2	IGF pathway	24	1,547	0.00018 (IGF1)	2	1.2	1.7	0.12
3	TGF-β superfamily and signaling pathway	49	2,878	0.0010(SMAD7)	2	2.5	0.8	0.45
4	Thrombophilia and vascular homeostasis	32	2,069	0.0014 (ADAMTS9)	0	1.6	0.0	0.81
5	Obesity and obesity-related phenotypes	36	2,437	0.00041 (EIF2B4)	3	1.8	1.7	0.10
7	Premature ovary failure	13	648	0.0087 (EIF2B5)	2	0.7	3.1	0.025
8	Polycystic ovary syndrome	18	2,013	1.0E-05 (NBN)	1	0.9	1.1	0.23
9	Smoking and nicotine dependence	49	3,300	0.00064 (GABBR2)	1	2.5	0.4	0.71
Total		259	17,519	1.0E-05 (NBN)	16	13.0	1.2	0.16

^aThe number of genes with significant associations at gene level;

^bThe expected number of significant genes under the null hypothesis at conventional significance level of 0.05;

^cp-values from the proportion test comparing the observed number of significant genes with the expected number of significant genes.