Table 3.
Validation cohort: comparative analysis of reproductive parameters corresponding to single-nucleotide variations rs11031005 and rs10835638
| Androl. Parameters | rs10835638 | rs11031005 | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Genotype | Additive linear model | Genotype | Additive linear model | |||||||
| GG (n = 803) | GT (n = 294) | TT (n = 26) | P | beta | TT (n = 831) | CT (n = 269) | CC (n = 23) | P | beta | |
| FSH, IU/l (1-7) | 5.8 ± 4.9 | 4.6 ± 3.2 | 3.6 ± 2.1 | 5.55e-07** | -0.29 (0.06) | 5.7 ± 4.8 | 4.6 ± 3.3 | 4 ± 2.3 | 4.71e-06** | -0.27 (0.06) |
| 4.4 (1.8-14.2) | 3.9 (1.5-10) | 3.1 (1.6-8) | 4.4 (1.8-14.1) | 3.8 (1.5-10.1) | 3.1 (1.9-8.7) | |||||
| LH, IU/l (2-10) | 3.6 ± 1.8 | 3.8 ± 2.3 | 3.9 ± 1.4 | 1.63e-01 | 0.08 (0.06) | 3.6 ± 1.8 | 3.8 ± 2.4 | 4 ± 1.4 | 3.64e-02* | 0.13 (0.06) |
| 3.2 (1.5-6.6) | 3.2 (1.5-7) | 3.5 (2.2-6.4) | 3.2 (1.5-6.6) | 3.2 (1.5-7.2) | 3.8 (2.2-6.6) | |||||
| FSH/LH | 1.7 ± 1.2 | 1.3 ± 0.7 | 1 ± 0.8 | 6.4e-12** | -0.4 (0.06) | 1.7 ± 1.2 | 1.3 ± 0.6 | 1.1 ± 0.9 | 2.08e-12** | -0.42 (0.06) |
| 1.4 (0.6-3.6) | 1.2 (0.5-2.7) | 0.8 (0.5-1.6) | 1.4 (0.6-3.6) | 1.2 (0.4-2.5) | 0.8 (0.5-1.7) | |||||
| Testosterone, nmol/l (≥ 12) | 16.4 ± 6.4 | 16.2 ± 6.2 | 18.7 ± 7 | 8.75e-01 | 0.01 (0.06) | 16.5 ± 6.4 | 16 ± 6.1 | 18.2 ± 6.9 | 7.36e-01 | -0.02 (0.06) |
| 15.3 (9.1-27.3) | 14.9 (9.2-25.7) | 15.6 (11.5-29.1) | 15.3 (9.1-27.6) | 14.9 (8.9-25) | 15.5 (11.4-28.4) | |||||
| Bitestic. Volume, ml | 41.8 ± 14.2 | 40 ± 13.3 | 35 ± 13.3 | 4.93e-03* | -0.16 (0.06) | 41.8 ± 14.2 | 39.8 ± 13.2 | 35 ± 13.7 | 5.42e-03* | -0.17 (0.06) |
| 40 (22-67) | 39 (21-64.3) | 34 (19.8-52) | 40 (22-67) | 39 (21-64.6) | 34 (19.4-52.6) | |||||
| Ejaculate volume, ml | 3.9 ± 1.6 | 3.7 ± 1.6 | 4 ± 1.4 | 3.04e-01 | -0.06 (0.06) | 3.9 ± 1.6 | 3.8 ± 1.6 | 4.1 ± 1.5 | 7.9e-01 | -0.02 (0.06) |
| 3.6 (1.8-7) | 3.4 (1.8-7) | 3.9 (1.8-6.8) | 3.5 (1.8-7) | 3.5 (1.8-7.1) | 4 (1.8-6.9) | |||||
| Total sperm count, Mill/ejac | 113.5 ± 169.8 | 98.6 ± 127.2 | 108.9 ± 130.8 | 9.25e-01 | -0.01 (0.06) | 112.4 ± 168.4 | 101.2 ± 128.5 | 103.6 ± 129.1 | 8.93e-01 | 0.01 (0.06) |
| 59 (1.9-371.3) | 52.5 (3.1-370.3) | 51.7 (2.9-365.6) | 58.3 (1.9-371.4) | 55 (3.1-363) | 37.4 (2.9-367.3) | |||||
| Sperm conc., Mill/ml | 30.6 ± 43 | 28.9 ± 37 | 32.1 ± 42.9 | 7.4e-01 | 0.02 (0.06) | 30.5 ± 42.7 | 29.3 ± 37.6 | 29.1 ± 40.2 | 7.36e-01 | 0.02 (0.06) |
| 17 (0.6-103.1) | 15.1 (0.8-108.4) | 14.2 (0.7-121.5) | 16.9 (0.6-103.4) | 15.4 (0.8-109.9) | 13 (0.6-95) | |||||
| Sperm ab-motility, % | 43.5 ± 13.2 | 42.6 ± 13.4 | 40.5 ± 13.8 | 1.61e-01 | -0.08 (0.06) | 43.5 ± 13.2 | 42.5 ± 13.2 | 40.2 ± 14 | 1.31e-01 | -0.09 (0.06) |
| 47 (17-59) | 46 (17.6-58) | 42 (17-57) | 47 (17-60) | 45 (17-58) | 40 (16.4-57) | |||||
| Sperm morphology | 4.4 ± 2.5 | 4.6 ± 2.7 | 4.6 ± 2.2 | 5.09e-01 | 0.04 (0.06) | 4.4 ± 2.5 | 4.7 ± 2.8 | 4.5 ± 2.3 | 3.85e-01 | 0.06 (0.07) |
| 4 (1-9) | 4 (1-10.8) | 5 (1-7) | 4 (1-9) | 4 (1-11) | 5 (1-7.3) | |||||
Two of the 9 identified single-nucleotide variations (discovery study) were analyzed via reverse transcriptase–polymerase chain reaction in an independent validation cohort (n = 1140 men with idiopathic infertility). Data are presented as mean ± SD and median (5th-95th percentile). Genotype-trait associations are calculated using an additive linear model with age added as a covariate. For sperm parameters, abstinence time was also included as a covariate.
Trends are marked in italics (*P < .05).
Statistically significant associations are marked in bold (**P < 2.50e-03).
Abbreviations: Androl., andrological; Bitestic, bitesticular; conc., concentration; ejac, ejaculation; FSH, follicle-stimulating hormone; LH, luteinizing hormone.