Table 1.
Mendelian randomization studies of various exposures with PCOS as the outcome
| Exposure | Year | Authors | Population of exposure | Population of outcome | SNPs, n | Effect | P-value |
|---|---|---|---|---|---|---|---|
| BMI | 2015 | Day et al | 249 796 Europeans | 6368 cases and 88 558 controls, European | 32 | OR: 1.90 (1.55, 2.34) | 2.5E-09 |
| BMI | 2018 | Day et al | 339 224 individuals (Europeans and non-Europeans) | 10 074 cases and 103 164 controls, European | NR | Beta: 0.72 (0.072) | 1.56E-23 |
| BMI | 2019 | Brower et al | 339 224 individuals (Europeans and non-Europeans) | 750 PCOS cases and 1567 BMI-matched controls, European | 92 | OR: 4.89 (1.46, 16.32) | NR |
| BMI | 2020 | Zhao et al | up to 173 430 East Asians | 4386 cases and 8017 controls, East Asians | 78 | OR: 2.21 (1.54, 3.17) | 1.77E-05 |
| BMI | 2020 | Ahn et al | 9953 Korean women | 946 PCOS cases and 976 controls, Korean | 3 | Beta: −0.124 (0.153) | 0.42 |
| Favorable adiposity | 2021 | Martin et al | UKBB, 451 099 Europeans | FinnGen + Day et al PCOS GWAS, 10 536 cases and 340 236 controls | 36 | OR: 0.51 (0.21, 1.23) | 0.13 |
| Unfavorable adiposity | 2021 | Martin et al | UKBB, 451 099 Europeans | FinnGen + Day et al PCOS GWAS, 10 536 cases and 340 236 controls | 38 | OR: 7.13 (3.66, 13.90) | 8.0E-09 |
| Testosterone | 2020 | Ruth et al | UKBB, 188 507 individuals | 4890 cases and 20 405 controls, European | 133 | OR: 1.55 (1.32, 1.82) | 1.9E-07 |
| SHBG | 2020 | Ruth et al | UKBB, 189 473 individuals | 4890 cases and 20 405 controls, European | 214 | OR: 0.69 (0.58, 0.81) | 1.9E-05 |
| SHBG | 2015 | Day et al | 28 837 Europeans | 6368 cases and 88 558 controls, European | 20 | OR: 0.86 (0.78, 0.93) | 5.4E-04 |
| AMH | 2020 | Verdiesen et al | 7049 premenopausal European women | 4890 cases and 20 405 controls, European | 4 | OR: 1.29 (0.85, 1.95) | 0.23 |
| DHEAS | 2015 | Day et al | 14 846 Europeans | 5184 cases and 82 759 controls, European | 8 | OR: 1.11 (0.99, 1.23) | 0.06 |
| Age at menopause | 2015 | Day et al | 92 371 Europeans | 6368 cases and 88 558 controls, European | 18 | OR: 1.60 (1.35, 1.91) | 1.5E-08 |
| Menopause timing | 2018 | Day et al | 92 371 Europeans | 10 074 cases and 103 164 controls, European | NR | Beta: 0.1 (0.022) | 1.31E-05 |
| Age at menarche | 2015 | Day et al | Up to 182 416 European women | 5184 cases and 82 759 controls, European | 113 | OR: 0.91 (0.79, 1.06) | 0.23 |
| Insulin resistance | 2015 | Day et al | Up to 18 565 Europeans | 6368 cases and 88 558 controls, European | 10 | OR: 1.11 (1.05, 1.19) | 5.6E-04 |
| Fasting insulin | 2018 | Day et al | 85 573 nondiabetic Europeans | 10 074 cases and 103 164 controls, European | NR | Beta: 0.03 (0.007) | 1.73E-05 |
| Insulin secretion | 2015 | Day et al | Up to 18 565 Europeans | 5184 cases and 82 759 controls, European | 23 | Higher risk | 0.19 |
| HDL cholesterol | 2015 | Day et al | >100 000 Europeans | 5184 cases and 82 759 controls, European | 71 | OR: 0.37 (0.13, 1.11) | 0.08 |
| LDL cholesterol | 2015 | Day et al | >100 000 Europeans | 5184 cases and 82 759 controls, European | 58 | OR: 1.04 (0.94, 1.16) | 0.43 |
| Total cholesterol | 2015 | Day et al | >100 000 Europeans | 5184 cases and 82 759 controls, European | 74 | OR: 0.98 (0.88, 1.09) | 0.71 |
| Triglycerides | 2015 | Day et al | >100 000 Europeans | 5184 cases and 82 759 controls, European | 40 | OR: 1.03 (0.90, 1.18) | 0.65 |
| Diastolic BP | 2015 | Day et al | 200 000 Europeans | 5184 cases and 82 759 controls, European | 26 | OR: 1.01 (0.99, 1.03) | 0.24 |
| Systolic BP | 2015 | Day et al | 200 000 Europeans | 5184 cases and 82 759 controls, European | 25 | OR: 1.05 (0.82, 1.34) | 0.68 |
| Male pattern balding | 2018 | Day et al | 52 874 white British men from UKBB | 10 074 cases and 103 164 controls, European | NR | Beta: 0.05 (0.017) | 0.0034 |
| Depression | 2018 | Day et al | 135 458 cases and 344 901 controls, European | 10 074 cases and 103 164 controls, European | NR | Beta: 0.77 (0.213) | 0.00029 |
| Birth weight | 2015 | Day et al | up to 69 308 Europeans | 5184 cases and 82 759 controls, European | 6 | Higher risk | 0.22 |
| Adult height | 2015 | Day et al | 183 727 Europeans | 5184 cases and 82 759 controls, European | 178 | Lower risk | 0.51 |
| Education years | 2020 | Adams et al | 293 723 Europeans | UKBB, 571 cases and 462 362 controls | 68 | OR: 1.00 (1.00, 1.00) | 0.28 |
| Periodontitis | 2021 | Wu et al | 12 289 cases and 22 326 controls, European | 4890 cases and 20 405 controls, European | 7 | OR: 1.17 (0.91, 1.49) | 0.21 |
| Beta-hydroxyisovalerate | 2020 | Sun et al | 7824 adult individuals, European | 4890 cases and 20 405 controls, European | 25 | OR: 2.84 (1.20, 6.76) | 0.0179 |
| 3-Dehydrocarnitine | 2020 | Sun et al | 7824 adult individuals, European | 4890 cases and 20 405 controls, European | 27 | OR: 6.72 (2.22, 20.32) | 0.0007 |
| Dihomolinolenate (20:3n3 or n6) | 2020 | Sun et al | 7824 adult individuals, European | 4890 cases and 20 405 controls, European | 25 | OR: 3.22 (1.21, 8.59) | 0.0194 |
| 1-Arachidonoylglycerophosphoethanolamine | 2020 | Sun et al | 7824 adult individuals, European | 4890 cases and 20 405 controls, European | 29 | OR: 2.97 (1.20, 7.36) | 0.0187 |
| 2-Linoleoylglycerophosphocholine | 2020 | Sun et al | 7824 adult individuals, European | 4890 cases and 20 405 controls, European | 22 | OR: 2.71 (1.05, 7.01) | 0.0402 |
| Hexanoylcarnitine | 2020 | Sun et al | 7824 adult individuals, European | 4890 cases and 20 405 controls, European | 23 | OR: 2.65 (1.35, 5.19) | 0.0045 |
| Hexadecanedioate | 2020 | Sun et al | 7824 adult individuals, European | 4890 cases and 20 405 controls, European | 26 | OR: 1.79 (1.11, 2.88) | 0.0161 |
| Epiandrosterone sulfate | 2020 | Sun et al | 7824 adult individuals, European | 4890 cases and 20 405 controls, European | 15 | OR: 1.54 (1.08, 2.21) | 0.0186 |
| 2-Tetradecenoyl carnitine | 2020 | Sun et al | 7824 adult individuals, European | 4890 cases and 20 405 controls, European | 19 | OR: 0.52 (0.30, 0.90) | 0.0193 |
| 7-Alpha-hydroxy-3-oxo-4-cholestenoate (7-Hoca) | 2020 | Sun et al | 7824 adult individuals, European | 4890 cases and 20 405 controls, European | 16 | OR: 0.16 (0.04, 0.68) | 0.0132 |
| N2,N2-Dimethylguanosine | 2020 | Sun et al | 7824 adult individuals, European | 4890 cases and 20 405 controls, European | 64 | OR: 0.39 (0.18, 0.85) | 0.0186 |
| Glycylvaline | 2020 | Sun et al | 7824 adult individuals, European | 4890 cases and 20 405 controls, European | 7 | OR: 2.11 (1.14, 3.89) | 0.017 |
| 4-Hydroxyhippurate | 2020 | Sun et al | 7824 adult individuals, European | 4890 cases and 20 405 controls, European | 11 | OR: 2.95 (1.24, 7.05) | 0.0148 |
Effect data are given as beta (SE) or odds ratio (95% CI).
Abbreviations: AMH, anti-Müllerian hormone; BMI, body mass index; BP, blood pressure; DHEAS, dehydroepiandrosterone sulfate; HDL, high-density lipoprotein; LDL, low-density lipoprotein; NR, not reported; OR, odds ratio; PCOS, polycystic ovary syndrome; SHBG, sex hormone-binding globulin; SNPs, SNPs, single nucleotide polymorphisms; UKBB, UK Biobank.