Multi-ancestry GWAS of diarrhea during acute SARS-CoV2 infection identifies multiple novel loci and contrasting etiological roles of irritable bowel syndrome subtypes

Author:

Chaudhary Ninad S.,Weldon Catherine H.,Nandakumar Priyanka,Shelton Janie F., ,Holmes Michael V.,Aslibekyan Stella

Abstract

ABSTRACTA substantial proportion of acute SARS-CoV2 infection cases exhibit gastrointestinal symptoms, yet the genetic determinants of these extrapulmonary manifestations are poorly understood. Using survey data from 239,866 individuals who tested positively for SARS-CoV2, we conducted a multi-ancestry GWAS of 80,289 cases of diarrhea occurring during acute COVID-19 infection (33.5%). Six loci (CYP7A1, LZFTL1- -CCR9, TEME182, NALCN, LFNG, GCKR) met genome-wide significance in a trans-ancestral analysis. The top significant GWAS hit mapped to theCYP7A1locus, which plays an etiologic role in bile acid metabolism and is in high LD (r2= 0.93) with theSDCBPgene, which was previously implicated in antigen processing and presentation in the COVID-19 context. Another association was observed with variants in theLZTFL1–CCR9region, which is a known locus for COVID-19 susceptibility and severity. PheWAS showed a shared association across three of the six SNPs with irritable bowel syndrome (IBS) and its subtypes. Mendelian randomization showed that genetic liability to IBS-diarrhea increased (OR=1.40,95%,CI[1.33-1.47]), and liability to IBS-constipation decreased (OR=0.86, 95%CI[0.79-0.94]) the relative odds of experiencing COVID-19+ diarrhea. Our genetic findings provide etiological insights into the extrapulmonary manifestations of acute SARS-CoV2 infection.

Publisher

Cold Spring Harbor Laboratory

Reference53 articles.

1. Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19: a systematic review and meta-analysis;Lancet Gastroenterol. Hepatol,2020

2. Prevalence of Gastrointestinal Symptoms and Fecal Viral Shedding in Patients With Coronavirus Disease 2019: A Systematic Review and Meta-analysis. JAMA Netw;Open,2020

3. AGA Institute Rapid Review of the Gastrointestinal and Liver Manifestations of COVID-19, Meta-Analysis of International Data, and Recommendations for the Consultative Management of Patients with COVID-19;Gastroenterology,2020

4. Pathophysiological mechanisms of liver injury in COVID-19;Liver Int. Off. J. Int. Assoc. Study Liver,2021

5. Gastrointestinal symptoms of 95 cases with SARS-CoV-2 infection

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3