Table 2. Variants significantly associated with hormone levels (P<5 × 10−8).
| Hormonea | Chr-positionb | SNP id | Imputation quality | Minor allele frequency | Minor allele effect (% of sd)c | P-value | Location (gene) | Best candidate (distance) | Comments |
|---|---|---|---|---|---|---|---|---|---|
| DHEAS | chr7.hg19:g.99075038 T>C | rs148982377T>C | 0.927 | 0.038 | −53.1 | 1.82 × 10−14 | ZNF789 (intron) | CYP3A7 (228 kb) | Published signal for DHEAS.d Same signal as rs34670419 (progesterone)e |
| FAI | chr16.hg19:g.52947630 A>C | rs117145500A>C | 0.959 | 0.063 | −35.9 | 1.50 × 10−8 | intergenic | LOC643714 (307 kb) | New signal |
| FSH | chr11.hg19:g.30226356 T>C | rs11031005T>C | 0.978 | 0.129 | −23.2 | 1.74 × 10−8 | intergenic | FSHB (26 kb) | New signal. Overlaps with LH signal (rs11031002)e |
| LH | chr11.hg19:g.30215261 T>A | rs11031002T>A | 0.971 | 0.121 | 25.2 | 3.94 × 10−9 | intergenic | FSHB (37 kb) | New signal. Overlaps with FSH signal (rs11031005)e |
| Oestradiol | chr12.hg19:g.6011490C>A | rs117585797C>A | 0.572 | 0.013 | 87.1 | 1.63 × 10−8 | ANO2 (intron) | ANO2 (intronic) | New signal |
| Progesterone | chr7.hg19:g.99130834G>T | rs34670419G>T | 0.927 | 0.037 | −55.6 | 6.09 × 10−14 | ZKSCAN5 (3' UTR) | CYP3A4 (224 kb) or CYP3A7 (172 kb) | Published signal for DHEAS.d Same signal as rs148982377 (DHEAS)e |
| Progesterone | chr11.hg19:g.62915346C>G | rs112295236C>G | 0.962 | 0.062 | 41.0 | 7.68 × 10−12 | intergenic | SLC22A9 (222 kb) | New signal |
| SHBG | chr17.hg19:g.7574775C>T | rs1641549C>T | 0.895 | 0.239 | −28.0 | 1.21 × 10−15 | TP53 (intron) | SHBG (38 kb) | Published signal for testosteroned |
Abbreviations: Chr, chromosome; DHEAS, dehydroepiandrosterone sulphate; FAI, free androgen index; FSH, follicle-stimulating hormone; LH, luteinizing hormone; sd, standard deviation; SHBG, sex hormone binding globulin; UTR, untranslated region.
Results are for square root of the DHEAS residuals and FAI residuals; inverse rank normal transformed FSH residuals and LH residuals; log10 of the oestradiol residuals and progesterone residuals; and ln of the SHBG residuals.
Details of the reference sequence on which the variant descriptions are based is given in the Supplementary information.
Minor allele effect sizes are quoted as a per-allele change expressed as a percentage of a standard deviation in the covariate-adjusted transformed residuals.
Further details regarding the published genetic variants associated with reproductive hormones are given in Supplementary Table 2.
Effect sizes and P-values for each signal in each hormone phenotype are given in Supplementary Table 3.