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IF 2.3 3区医学 Q2 SURGERY

World Journal of Surgery Pub Date : 2025-04-08 DOI:10.1002/wjs.12575

Apostolos Gaitanidis, Mathias A Christensen, Ander Dorken Gallastegi, Kerry A Breen, George C Velmahos, Haytham M A Kaafarani, Maha R Farhat

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引用次数: 0

摘要

背景：肠旋转不良是一种先天性胚胎肠道畸形，可导致儿童或成人中肠下垂。我们对其遗传背景的了解来自于有关综合征或家族性畸形的报道，目前还没有全基因组关联研究（GWAS）的报道。我们进行了首次全基因组关联研究，以确定与这种畸形相关的常见变异：方法：作为麻省总医院布里格姆生物库（Mass General Brigham Biobank）的一部分，我们对受试者进行了登记和基因分型，并对确诊为肠旋转不良的个体进行了鉴定。采用混合线性模型关联分析法检测小等位基因频率≥5%的单核苷酸多态性（SNPs）与肠旋转不良的关联。超过显著性阈值（p 结果）的 SNPs 被排除在外：衍生队列包括 11106 人（70 [0.6%] 例），验证队列包括 4134 人（21 [0.5%] 例）。染色体 17p13（主导 SNP rs75147837，beta = 0.0044，p = 7.97E-10）和 10q26（主导 SNP rs3121846，beta = 0.0057，p = 3.28E-08）两个位点上的五个外显子 SNP 具有 p 结论：我们报告了首个关于肠旋转不良的 GWAS 结果。位于 17p13 的一个位点与肠旋转不良有关，该位点可指导遗传学研究，并提高我们对这种畸形的认识。研究发现，Rs72631499 是 HNF4A 的结合位点，HNF4A 是一种转录因子，在正常胚胎肠道发育中发挥着重要作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Genome-Wide Association Study Identifies a Locus at 17p13 to Be Associated With Intestinal Malrotation.

Background: Intestinal malrotation is a congenital malformation of the embryonic gut that may cause midgut volvulus either in children or adults. Our understanding of its genetic background stems from reports of syndromic or familial forms and no genome-wide association studies (GWAS) have been reported. We perform the first GWAS to identify common variants associated with this malformation.

Methods: Subjects were enrolled and genotyped as part of the Mass General Brigham Biobank and individuals with diagnosis of intestinal malrotation were identified. Single nucleotide polymorphisms (SNPs) with minor allele frequency ≥ 5% were examined for association with intestinal malrotation using mixed linear model association analysis. SNPs that surpassed the significance threshold (p < 5E-08) were further examined in a separate validation cohort.

Results: The derivation cohort included 11,106 individuals (70 [0.6%] cases), and the validation cohort included 4134 individuals (21 [0.5%] cases). Five exonic SNPs in two loci at chromosomes 17p13 (lead SNP rs75147837, beta = 0.0044, and p = 7.97E-10) and 10q26 (lead SNP rs3121846, beta = 0.0057, p = 3.28E-08) had p < 5E-08. After validation, 2 SNPs at 17p13 were associated with the phenotype (rs72631499 adjusted-p = 0.010 and rs148094507 adjusted-p = 0.014). eQTL (expression Quantitative Trait Loci) analysis mapped 6 genes to the identified locus (PITPNA, TRARG1, INPP5K, YWHAE, PITPNA-AS1, and FAM57A).

Conclusion: We report results from the first GWAS on intestinal malrotation. A locus at 17p13 is associated with intestinal malrotation and may guide genetic guidance and improve our understanding of this malformation. Rs72631499 was found to be a binding site for HNF4A, a transcription factor that plays important roles in normal embryonic gut development.

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来源期刊

World Journal of Surgery 医学-外科

CiteScore

5.10

自引率

3.80%

发文量

460

审稿时长

3 months

期刊介绍： World Journal of Surgery is the official publication of the International Society of Surgery/Societe Internationale de Chirurgie (iss-sic.com). Under the editorship of Dr. Julie Ann Sosa, World Journal of Surgery provides an in-depth, international forum for the most authoritative information on major clinical problems in the fields of clinical and experimental surgery, surgical education, and socioeconomic aspects of surgical care. Contributions are reviewed and selected by a group of distinguished surgeons from across the world who make up the Editorial Board.