XiaoJu Wan, XiaoBao Lai, MeiZhen Huang, Min Yu, Tao Ding, ZhiHui Huang, ZhiQin Zhang, XingWu Wu, Jun Tan
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Two large-scale GWAS mtDNA copy number datasets were employed for testing and validation to ensure reliable results.</p><p><strong>Results: </strong>According to the forward MR analysis, genetically predicted mtDNA copy number was not associated with premature ovarian failure (POF) (OR = 1.969, 95% CI 0.571-6.789; <i>p</i> = .283), polycystic ovary syndrome (PCOS) (OR = 0.821, 95% CI 0.314-2.142; <i>p</i> = .686), endometriosis (OR = 1.281, 95% CI 0.962-1.704; <i>p</i> = 0.090), or female infertility (OR = 0.966; 95% CI 0.744-1.253; <i>p</i> = .794) but was associated with intestinal endometriosis (OR = 7.528; 95% CI 1.654-34.262; <i>p</i> = .009) and adenomyosis (OR = 1.710; 95% CI 1.118-2.616; <i>p</i> = .013). Reverse MR studies did not reveal a correlation between female infertility and mtDNA copy number. Similar results were observed in the validation data.</p><p><strong>Conclusions: </strong>Our study suggested that there is no causal relationship between mtDNA copy number and female infertility, but there is a causal relationship between mtDNA copy number and intestinal endometriosis and adenomyosis. The genetic evidence provided by this study provides a new perspective for studying the impact of mtDNA copy number on female infertility.</p>","PeriodicalId":12865,"journal":{"name":"Gynecological Endocrinology","volume":"40 1","pages":"2444380"},"PeriodicalIF":2.0000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The role of mitochondrial DNA copy number in female infertility: a bidirectional two-sample Mendelian randomization study.\",\"authors\":\"XiaoJu Wan, XiaoBao Lai, MeiZhen Huang, Min Yu, Tao Ding, ZhiHui Huang, ZhiQin Zhang, XingWu Wu, Jun Tan\",\"doi\":\"10.1080/09513590.2024.2444380\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Previous studies on the impact of mitochondrial DNA (mtDNA) copy number on female infertility were limited and inconsistent.</p><p><strong>Methods: </strong>The causal relationship between mtDNA copy number and female infertility was evaluated using a bidirectional 2-sample Mendelian randomization (MR) method. Inverse variance weighted (IVW) method was applied for principal analysis, and MR-Egger, weighted median, simple mode, weighted mode method for secondary analyses. Sensitivity analysis was conducted using MR-PRESSO, MR-Egger, Cochran's Q, and leave-one-out tests. Two large-scale GWAS mtDNA copy number datasets were employed for testing and validation to ensure reliable results.</p><p><strong>Results: </strong>According to the forward MR analysis, genetically predicted mtDNA copy number was not associated with premature ovarian failure (POF) (OR = 1.969, 95% CI 0.571-6.789; <i>p</i> = .283), polycystic ovary syndrome (PCOS) (OR = 0.821, 95% CI 0.314-2.142; <i>p</i> = .686), endometriosis (OR = 1.281, 95% CI 0.962-1.704; <i>p</i> = 0.090), or female infertility (OR = 0.966; 95% CI 0.744-1.253; <i>p</i> = .794) but was associated with intestinal endometriosis (OR = 7.528; 95% CI 1.654-34.262; <i>p</i> = .009) and adenomyosis (OR = 1.710; 95% CI 1.118-2.616; <i>p</i> = .013). Reverse MR studies did not reveal a correlation between female infertility and mtDNA copy number. Similar results were observed in the validation data.</p><p><strong>Conclusions: </strong>Our study suggested that there is no causal relationship between mtDNA copy number and female infertility, but there is a causal relationship between mtDNA copy number and intestinal endometriosis and adenomyosis. 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引用次数: 0
摘要
背景:以往关于线粒体DNA (mtDNA)拷贝数对女性不孕症影响的研究有限且不一致。方法:采用双向双样本孟德尔随机化(MR)方法评估mtDNA拷贝数与女性不孕症的因果关系。主分析采用反方差加权(IVW)法,次分析采用MR-Egger、加权中位数、简单众数、加权众数法。敏感度分析采用MR-PRESSO、MR-Egger、Cochran’s Q和留一检验。采用两个大规模的GWAS mtDNA拷贝数数据集进行测试和验证,以确保结果的可靠性。结果:根据正向磁共振分析,遗传预测mtDNA拷贝数与卵巢早衰(POF)无关(OR = 1.969, 95% CI 0.571-6.789;p = 0.283),多囊卵巢综合征(PCOS) (OR = 0.821, 95% CI 0.314-2.142;p = .686),子宫内膜异位症(OR = 1.281, 95% CI 0.962-1.704;p = 0.090)或女性不育(or = 0.966;95% ci 0.744-1.253;p = .794),但与肠道子宫内膜异位症相关(OR = 7.528;95% ci 1.654-34.262;p = 0.009)和子宫腺肌症(OR = 1.710;95% ci 1.118-2.616;p = .013)。反向磁共振研究未发现女性不育与mtDNA拷贝数之间的相关性。在验证数据中也观察到类似的结果。结论:我们的研究提示mtDNA拷贝数与女性不孕无因果关系,但mtDNA拷贝数与肠道子宫内膜异位症和子宫腺肌症存在因果关系。本研究提供的遗传学证据为研究mtDNA拷贝数对女性不育的影响提供了新的视角。
The role of mitochondrial DNA copy number in female infertility: a bidirectional two-sample Mendelian randomization study.
Background: Previous studies on the impact of mitochondrial DNA (mtDNA) copy number on female infertility were limited and inconsistent.
Methods: The causal relationship between mtDNA copy number and female infertility was evaluated using a bidirectional 2-sample Mendelian randomization (MR) method. Inverse variance weighted (IVW) method was applied for principal analysis, and MR-Egger, weighted median, simple mode, weighted mode method for secondary analyses. Sensitivity analysis was conducted using MR-PRESSO, MR-Egger, Cochran's Q, and leave-one-out tests. Two large-scale GWAS mtDNA copy number datasets were employed for testing and validation to ensure reliable results.
Results: According to the forward MR analysis, genetically predicted mtDNA copy number was not associated with premature ovarian failure (POF) (OR = 1.969, 95% CI 0.571-6.789; p = .283), polycystic ovary syndrome (PCOS) (OR = 0.821, 95% CI 0.314-2.142; p = .686), endometriosis (OR = 1.281, 95% CI 0.962-1.704; p = 0.090), or female infertility (OR = 0.966; 95% CI 0.744-1.253; p = .794) but was associated with intestinal endometriosis (OR = 7.528; 95% CI 1.654-34.262; p = .009) and adenomyosis (OR = 1.710; 95% CI 1.118-2.616; p = .013). Reverse MR studies did not reveal a correlation between female infertility and mtDNA copy number. Similar results were observed in the validation data.
Conclusions: Our study suggested that there is no causal relationship between mtDNA copy number and female infertility, but there is a causal relationship between mtDNA copy number and intestinal endometriosis and adenomyosis. The genetic evidence provided by this study provides a new perspective for studying the impact of mtDNA copy number on female infertility.
期刊介绍:
Gynecological Endocrinology , the official journal of the International Society of Gynecological Endocrinology, covers all the experimental, clinical and therapeutic aspects of this ever more important discipline. It includes, amongst others, papers relating to the control and function of the different endocrine glands in females, the effects of reproductive events on the endocrine system, and the consequences of endocrine disorders on reproduction