Mendelian Randomization Study on the Causal Relationship between Different Endometriosis Subtypes and Serum Uric Acid Levels

doi:10.12280/gjfckx.20251363

Abstract

Abstract:

Objective: To explore the causal relationship between different subtypes of endometriosis (EMs) and serum uric acid (SUA) levels using Mendelian randomization (MR) analysis. Methods: The analysis utilized publicly available summary data from genome-wide association study (GWAS) of European ancestry. GWAS data for SUA were derived from the European subset of a trans-ancestry meta-analysis (sample size n=288 649). Exposure data for EMs and its subtypes were obtained from the Finnish population in the FinnGen cohort (total sample n=500 348, including 282 064 females). Seven EMs subtypes were analyzed: overall EMs, ASRM (American Society for Reproductive Medicine) stages Ⅲ-Ⅳ severe EMs, deep infiltrating EMs, ovarian EMs, pelvic peritoneal EMs, rectovaginal septum EMs, and uterine EMs. The inverse variance weighted (IVW) method served as the primary analysis. Complementary analyses were conducted using MR-Egger regression, weighted median, simple mode, and weighted mode methods. Heterogeneity was assessed using Cochran's Q test. Horizontal pleiotropy was evaluated via MR-Egger regression with its intercept test and the MR-PRESSO method. The robustness of results was tested using the leave-one-out sensitivity analysis. Results: In the forward MR analysis with EMs subtypes as exposures and SUA as the outcome, significant positive causal effects were observed for ASRM stage Ⅲ-Ⅳ severe EMs (β=0.025 9, SE=0.007 8, P=0.000 9), ovarian EMs (β=0.023 2, SE=0.006 6, P=0.000 4), and pelvic peritoneal EMs (β=0.025 2, SE=0.011 9, P=0.034 8), indicating these subtypes causally increased SUA levels. No significant causal effects were found for the other subtypes. Sensitivity analyses revealed no substantial heterogeneity or horizontal pleiotropy. In the reverse MR analysis with SUA as the exposure and EMs subtypes as outcomes, while all odds ratios from the IVW method were positive, none reached statistical significance (P>0.05). However, the weighted median method in the reverse analysis indicated statistically significant positive associations between SUA and the risk of ASRM stage Ⅲ-Ⅳ severe EMs and ovarian EMs (P<0.05). Conclusions: ASRM stage Ⅲ-Ⅳ severe EMs, ovarian EMs, and pelvic peritoneal EMs may causally increase SUA levels through genetic pathways. Conversely, evidence for a causal effect of elevated SUA on the risk of developing EMs was not significant.

Key words: Endometriosis, Uric acid, Mendelian randomization analysis, Genome-wide association study

DA Hui, XU Chuan-hua, HUANG Long-ping, YIN Xiang-han, ZHU Yuan-yuan. Mendelian Randomization Study on the Causal Relationship between Different Endometriosis Subtypes and Serum Uric Acid Levels[J]. Journal of International Obstetrics and Gynecology, 2026, 53(4): 430-437.

Figures/Tables 7

References 21

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亚型	表型编码	病例数（例）	对照数（例）	SNP（个）
EMs（总体表型）	N14_ENDOMETRIOSIS	20 190	130 160	20 445 427
ASRMⅢ~Ⅳ期EMs	N14_ENDOMETRIOSIS_ASRM_STAGE3_4	10 127	271 937	20 459 052
深部浸润型EMs	N14_ENDOMETRIOSIS_DEEP	3 806	271 937	20 458 731
卵巢型EMs	N14_ENDOMETRIOSIS_OVARY	7 878	130 160	20 441 679
盆腔腹膜型EMs	N14_ENDOMETRIOSIS_PELVICPERITONEUM	7 617	130 160	20 441 630
直肠阴道隔型EMs	N14_ENDOMETRIOSIS_RECTPVAGSEPT_VAGINA	3 226	130 160	20 440 157
子宫型EMs（子宫腺肌病）	N14_ENDOMETRIOSIS_UTERUS	5 673	130 160	20 441 278

亚型	表型编码	病例数（例）	对照数（例）	SNP（个）
EMs（总体表型）	N14_ENDOMETRIOSIS	20 190	130 160	20 445 427
ASRMⅢ~Ⅳ期EMs	N14_ENDOMETRIOSIS_ASRM_STAGE3_4	10 127	271 937	20 459 052
深部浸润型EMs	N14_ENDOMETRIOSIS_DEEP	3 806	271 937	20 458 731
卵巢型EMs	N14_ENDOMETRIOSIS_OVARY	7 878	130 160	20 441 679
盆腔腹膜型EMs	N14_ENDOMETRIOSIS_PELVICPERITONEUM	7 617	130 160	20 441 630
直肠阴道隔型EMs	N14_ENDOMETRIOSIS_RECTPVAGSEPT_VAGINA	3 226	130 160	20 440 157
子宫型EMs（子宫腺肌病）	N14_ENDOMETRIOSIS_UTERUS	5 673	130 160	20 441 278