Table 2.
Independent GWAS hits and their representative variants identified by either the additive or the recessive model
| SNPID (rsid) | Most severe consequence | Locus | AF cases | AF controls | OR (95% CI) | p value | Fin enrichmenta | Known associationsb |
|---|---|---|---|---|---|---|---|---|
| Recessive | ||||||||
| chr8_109459837_G_C (rs17368310)c,d | splice donor variant | PKHD1L1 | 0.077 | 0.067 | 2.34 (1.98–2.78) | 1.47 × 10−22 | 1.42 | female infertility |
| chr14_55424219_T_A (rs144313315)e | stop gained | TBPL2 | 0.013 | 0.012 | 650.1 (190.7–2216.1) | 4.11 × 10−25 | 43.04 | – |
| Additive | ||||||||
| chr1_22139327_T_C (rs61768001) | intron variant | WNT4 | 0.167 | 0.155 | 1.1 (1.07–1.13) | 4.4 × 10−12 | 0.99 | endometriosis, fibroids |
| chr4_69718365_T_G (rs13138435) | downstream gene variant | SULT1B1 | 0.299 | 0.313 | 0.93 (0.91–0.95) | 4.57 × 10−10 | 0.8 | uterine leiomyomata and fibroids |
| chr6_152241136_C_G (rs58415480) | intron variant | ESR1 | 0.246 | 0.231 | 1.08 (1.06–1.11) | 2.69 × 10−11 | 1.59 | endometriosis |
| chr6_151230382_G_T (rs35977392) | upstream gene variant | ESR1 | 0.340 | 0.354 | 0.93 (0.91–0.95) | 3.97 × 10−11 | 0.88 | endometriosis |
| chr8_109459837_G_C (rs17368310) | splice donor variant | PKHD1L1 | 0.077 | 0.067 | 1.19 (1.14–1.23) | 3.79 × 10−18 | 1.42 | female infertility |
The lead variant from the recessive and the additive models at the shared locus (PKHD1L1) are within the same credible set (linkage disequilibrium [LD] = 1). CI, confidence interval.
a
Compared to non-Finnish Europeans in gnomAD v.3.15
b
Known associations at the gene level have been defined from NHGRI-EBI GWAS Catalog16 and previous publications for female infertility and underlying disorders.
c
Representative variant was changed to coding variant from lead variant chr8_109515401_CAAT_C (rs58870933), r2 = 1.
d
c.7246+1G>C (GenBank: NM_177531.6).
e
c.895A>T (GenBank: NM_199047.3) (p.Arg299Ter).