Causal effects of genetic birth weight and gestational age on adult esophageal diseases: Mendelian randomization study

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS

ACS Applied Bio Materials Pub Date : 2024-07-15 DOI:10.4251/wjgo.v16.i7.3055

Liancheng Ruan, Yang Zhang, Lan Su, Lingxiao Zhu, Silin Wang, Qiang Guo, Bingen Wan, Shengyu Qiu, Sheng Hu, Yi-Ping Wei, Qiao-Ling Zheng

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Abstract

BACKGROUND Few studies have investigated the association between gestational age, birth weight, and esophageal cancer risk; however, causality remains debated. We aimed to establish causal links between genetic gestational age and birth weight traits and gastroesophageal reflux disease (GERD), Barrett’s esophagus (BE), and esophageal adenocarcinoma (EA). Additionally, we explored if known risk factors mediate these links. AIM To analyze of the relationship between gestational age, birth weight and GERD, BE, and EA. METHODS Genetic data on gestational age and birth weight (n = 84689 and 143677) from the Early Growth Genetics Consortium and outcomes for GERD (n = 467253), BE (n = 56429), and EA (n = 21271) from genome-wide association study served as instrumental variables. Mendelian randomization (MR) and mediation analyses were conducted using MR-Egger, weighted median, and inverse variance weighted methods. Robustness was ensured through heterogeneity, pleiotropy tests, and sensitivity analyses. RESULTS Birth weight was negatively correlated with GERD and BE risk [odds ratio (OR) = 0.78; 95% confidence interval (CI): 0.69-0.8] and (OR = 0.75; 95%CI: 0.60-0.9), respectively, with no significant association with EA. No causal link was found between gestational age and outcomes. Birth weight was positively correlated with five risk factors: Educational attainment (OR = 1.15; 95%CI: 1.01-1.31), body mass index (OR = 1.06; 95%CI: 1.02-1.1), height (OR = 1.12; 95%CI: 1.06-1.19), weight (OR = 1.13; 95%CI: 1.10-1.1), and alcoholic drinks per week (OR = 1.03; 95%CI: 1.00-1.06). Mediation analysis showed educational attainment and height mediated the birth weight-BE link by 13.99% and 5.46%. CONCLUSION Our study supports the protective role of genetically predicted birth weight against GERD, BE, and EA, independent of gestational age and partially mediated by educational attainment and height.

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遗传出生体重和胎龄对成年食管疾病的因果效应：孟德尔随机研究

背景很少有研究调查妊娠年龄、出生体重与食管癌风险之间的关联；然而，因果关系仍存在争议。我们旨在确定遗传性妊娠年龄和出生体重特征与胃食管反流病（GERD）、巴雷特食管（BE）和食管腺癌（EA）之间的因果关系。此外，我们还探讨了已知的风险因素是否会介导这些联系。目的分析胎龄、出生体重与胃食管反流病、BE 和 EA 之间的关系。方法早期生长遗传学联合会提供的妊娠年龄和出生体重的遗传数据（n = 84689 和 143677）以及全基因组关联研究提供的胃食管反流病（n = 467253）、BE（n = 56429）和 EA（n = 21271）的结果作为工具变量。使用 MR-Egger、加权中位数和反方差加权法进行了孟德尔随机化（MR）和中介分析。通过异质性、多效性检验和敏感性分析确保了稳健性。结果出生体重与胃食管反流病和 BE 风险呈负相关[几率比（OR）= 0.78；95% 置信区间（CI）：0.69-0.8]和（OR = 0.75；95%CI：0.60-0.9），与 EA 无显著关联。胎龄与结果之间没有因果关系。出生体重与五个风险因素呈正相关：教育程度（OR = 1.15；95%CI：1.01-1.31）、体重指数（OR = 1.06；95%CI：1.02-1.1）、身高（OR = 1.12；95%CI：1.06-1.19）、体重（OR = 1.13；95%CI：1.10-1.1）和每周饮酒量（OR = 1.03；95%CI：1.00-1.06）。中介分析表明，受教育程度和身高分别以 13.99% 和 5.46% 的中介作用调节出生体重与体重指数之间的联系。结论我们的研究支持遗传预测出生体重对胃食管反流病、BE 和 EA 的保护作用，这与胎龄无关，并部分受教育程度和身高的影响。

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来源期刊

ACS Applied Bio Materials Chemistry-Chemistry (all)

CiteScore

9.40

自引率

2.10%

发文量

464

期刊介绍： ACS Applied Bio Materials is an interdisciplinary journal publishing original research covering all aspects of biomaterials and biointerfaces including and beyond the traditional biosensing, biomedical and therapeutic applications. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrates knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important bio applications. The journal is specifically interested in work that addresses the relationship between structure and function and assesses the stability and degradation of materials under relevant environmental and biological conditions.