2024 年5 期 第32 卷
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儿童期体质指数与妊娠期高血压的潜在因果关系: 孟德尔随机化研究
Potential Causal Relationship between Childhood BMI and Gestational Hypertension: a Mendelian Randomization Study
作者:邢影,罗小平
- 单位:
- 430030湖北省武汉市,华中科技大学同济医学院附属同济医院儿童遗传内分泌呼吸科
- Units:
- Pediatric Genetic Endocrinology and Respiratory Department, Tongji Medical College of HUST, Wuhan 430030, China
- 关键词:
- 高血压,妊娠性;体质指数;儿童;孟德尔随机化分析
- Keywords:
- Hypertension, pregnancy-induced; Body mass index; Child; Mendelian randomization analysis
- CLC:
- R 714.246
- DOI:
- 10.12114/j.issn.1008-5971.2024.00.095
- Funds:
摘要:
目的 采用孟德尔随机化(MR)方法探讨儿童期体质指数(BMI)与妊娠期高血压(GH)的潜在因 果关系。方法 从全基因组关联研究(GWAS)数据库获取儿童期BMI数据集(ID:ebi-a-GCST90002409)和GH数据 集(ID:finn-b-O15_HYPTENSPREG),其中儿童期BMI数据集的样本量为39 620例,包括8 173 382个单核苷酸多态 性(SNP);GH数据集的样本量为123 579例,包括16 379 784个SNP。本研究采用逆方差加权法(IVW)、MR-Egger 回归、加权中位数法、简单模式法、加权模式法分析儿童期BMI与GH的潜在因果关系。采用Cochran Q检验评估各SNP 间的统计学异质性,采用MR-Egger回归的截距项、MR-PRESSO检验及漏斗图分析SNP的水平多效性,采用留一法评 估单个SNP对IVW分析结果的影响。结果 本研究共筛选出16个与儿童期BMI高度相关的SNP,剔除rs2076308(回文 SNP)、rs17817449(离群值)、rs61765651(离群值)后,最终纳入13个与儿童期BMI高度相关的SNP。IVW分析结 果显示,儿童期BMI升高是GH的危险因素〔OR=1.29,95%CI(1.09~1.53),P<0.01〕;且MR-Egger回归、加权中 位数法、简单模式法、加权模式法分析的β值与IVW分析的β值方向一致。Cochran Q检验结果显示,与儿童期BMI高 度相关的SNP间不存在统计学异质性(P=0.47)。MR-Egger回归的截距项、MR-PRESSO检验、漏斗图分析结果均显 示,与儿童期BMI高度相关的SNP不存在水平多效性。留一法分析结果显示,剔除单个SNP后,MR分析结果无明显改 变。结论 儿童期BMI升高是GH的危险因素。
Abstract:
Objective To analyze the potential causal relationship between childhood body mass index (BMI) and gestational hypertension (GH) through Mendelian randomization (MR) method. Methods The childhood BMI dataset (ID: ebi-a-GCST90002409) and GH dataset (ID: finn-b-O15_HYPTENSPREG) were obtained from the genome-wide association study (GWAS) database. The sample size of the childhood BMI dataset was 39 620, including 8 173 382 single nucleotide polymorphisms (SNPs) . The sample size of GH dataset was 123 579, including 16 379 784 SNPs. In this study, inverse variance weighting (IVW) , MR-Egger regression, weighted median method, simple model method and weighted model method were used to analyze the potential causal relationship between childhood BMI and GH. Cochran Q test was used to evaluate the statistical heterogeneity among SNPs. The intercept term of MR-Egger regression, MR-PRESSO test and funnel plot were used to analyze the level pleiotropy of SNPs. The effect of single SNPs on IVW analysis results was evaluated by leave-one-out method. Results A total of 16 SNPs highly correlated with childhood BMI were screened in this study. After excluding rs2076308 (palindrome SNP) , rs17817449 (outlier) and rs61765651 (outlier) , 13 SNPs highly correlated with childhood BMI were finally included. IVW analysis results showed that increased childhood BMI was a risk factor for GH [OR=1.29, 95%CI (1.09-1.53) , P < 0.01] . The β values of MR-Egger regression, weighted median method, simple mode method and weighted mode method were consistent with the β value of IVW. The results of Cochran Q test showed that there was no statistical heterogeneity among SNPs highly correlated with childhood BMI (P=0.47) . The results of intercept term of MR-Egger regression, MR-PRESSO test and funnel plot analysis showed that there was no level pleiotropy in SNPs highly correlated with childhood BMI. The results of leave-one-out analysis showed that there was no significant change in MR analysis results after removing a single SNP. Conclusion Increased childhood BMI is a risk factor for GH.
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