Volume 151, Issue 2, Pages e28 (August 2016)

Slides:

Advertisements

Similar presentations

Kyung Won Kim, MD, PhD, Rachel A

Advertisements

Ursodeoxycholic Acid and Diets Higher in Fat Prevent Gallbladder Stones During Weight Loss: A Meta-analysis of Randomized Controlled Trials Caroline.

The Value of a 24/7 Online Nationwide Multidisciplinary Expert Panel for Acute Necrotizing Pancreatitis Janneke van Grinsven, Sandra van Brunschot Gastroenterology

Pancreatic Fusion Abnormality Found During a Whipple Procedure

Inflammatory Markers Are Associated With Risk of Colorectal Cancer and Chemopreventive Response to Anti-Inflammatory Drugs Andrew T. Chan, Shuji Ogino,

Pigmentation-Independent Susceptibility Loci for Actinic Keratosis Highlighted by Compound Heterozygosity Analysis Kaiyin Zhong, Joris A.C. Verkouteren,

Immunology and the Lynch Syndrome

Volume 153, Issue 2, Pages (August 2017)

Volume 141, Issue 1, Pages (July 2011)

Volume 136, Issue 2, Pages (February 2009)

The Value of a 24/7 Online Nationwide Multidisciplinary Expert Panel for Acute Necrotizing Pancreatitis Janneke van Grinsven, Sandra van Brunschot Gastroenterology

Covering the Cover Gastroenterology

Volume 141, Issue 2, Pages (August 2011)

Volume 152, Issue 3, Pages e5 (February 2017)

Accuracy of Spleen Stiffness Measurement in Detection of Esophageal Varices in Patients With Chronic Liver Disease: Systematic Review and Meta-analysis

Ursodeoxycholic Acid and Diets Higher in Fat Prevent Gallbladder Stones During Weight Loss: A Meta-analysis of Randomized Controlled Trials Caroline.

Outcomes Among Living Liver Donors

Volume 143, Issue 1, Pages e4 (July 2012)

Cigarette Smoking and Adenomatous Polyps: A Meta-analysis

Pancreatic Fusion Abnormality Found During a Whipple Procedure

Volume 139, Issue 6, Pages e2 (December 2010)

Volume 139, Issue 4, Pages e3 (October 2010)

Combined Analysis of Genome-wide Association Studies for Crohn Disease and Psoriasis Identifies Seven Shared Susceptibility Loci David Ellinghaus, Eva.

Meta-analysis of 65,734 Individuals Identifies TSPAN15 and SLC44A2 as Two Susceptibility Loci for Venous Thromboembolism Marine Germain, Daniel I. Chasman,

Effectiveness of Colorectal Cancer Screening in Detecting Earlier-Stage Disease—A Nationwide Cohort Study in Denmark Mette Bach Larsen, Sisse Njor, Peter.

Volume 135, Issue 3, Pages e10 (September 2008)

Volume 149, Issue 6, Pages e1 (November 2015)

The MC1R Gene and Youthful Looks

Association Between Consumption of Red and Processed Meat and Pancreatic Cancer Risk: A Systematic Review and Meta-analysis Zhanwei Zhao, Zifang Yin,

Volume 155, Issue 1, Pages (July 2018)

Weight Loss after Gastric Bypass Is Associated with a Variant at 15q26

Volume 139, Issue 1, Pages e24 (July 2010)

Volume 139, Issue 5, Pages e6 (November 2010)

Volume 142, Issue 6, Pages e3 (May 2012)

Immunology and the Lynch Syndrome

An Unusual Case Presented With Multiple Liver Cystic Lesions

Genome-wide Association Study Identifies Four Genetic Loci Associated with Thyroid Volume and Goiter Risk Alexander Teumer, Rajesh Rawal, Georg Homuth,

Meta-analysis Shows That Prevalence of Epstein–Barr Virus-Positive Gastric Cancer Differs Based on Sex and Anatomic Location Gwen Murphy, Ruth Pfeiffer,

Gene Expression in Skin and Lymphoblastoid Cells: Refined Statistical Method Reveals Extensive Overlap in cis-eQTL Signals Jun Ding, Johann E. Gudjonsson,

Volume 151, Issue 2, Pages e6 (August 2016)

Volume 143, Issue 5, Pages (November 2012)

Genome-Wide Association Studies: Present Status and Future Directions

Volume 25, Issue 24, Pages (December 2015)

Volume 153, Issue 2, Pages (August 2017)

Expression Quantitative Trait Loci Analysis Identifies Associations Between Genotype and Gene Expression in Human Intestine Boyko Kabakchiev, Mark S.

Inflammatory Markers Are Associated With Risk of Colorectal Cancer and Chemopreventive Response to Anti-Inflammatory Drugs Andrew T. Chan, Shuji Ogino,

Loci Related to Metabolic-Syndrome Pathways Including LEPR,HNF1A, IL6R, and GCKR Associate with Plasma C-Reactive Protein: The Women's Genome Health Study

Structural Architecture of SNP Effects on Complex Traits

Histologic Changes in Liver Tissue From Patients With Chronic Hepatitis B and Minimal Increases in Levels of Alanine Aminotransferase: A Meta-analysis.

Eva Ellinghaus, Philip E. Stuart, David Ellinghaus, Rajan P

Volume 138, Issue 5, Pages (May 2010)

Volume 133, Issue 2, Pages (August 2007)

Five Years of GWAS Discovery

Volume 377, Issue 9766, Pages (February 2011)

Accuracy of Spleen Stiffness Measurement in Detection of Esophageal Varices in Patients With Chronic Liver Disease: Systematic Review and Meta-analysis

Covering the Cover Gastroenterology

Volume 142, Issue 3, Pages (March 2012)

Javier Oliver, Blanca Rueda, Miguel A

Covering the Cover Gastroenterology

Volume 148, Issue 5, Pages e4 (May 2015)

Hunting for Celiac Disease Genes

Volume 156, Issue 5, Pages e7 (April 2019)

Daniel Mønsted Shabanzadeh, Lars Tue Sørensen, Torben Jørgensen

End-Stage Liver Disease in 2008: Finally a Glass Half Full

Genome-wide Linkage and Association Analyses Implicate FASN in Predisposition to Uterine Leiomyomata Stacey L. Eggert, Karen L. Huyck, Priya Somasundaram,

Electronic Clinical Challenges and Images in GI

Volume 27, Issue 11, Pages e4 (June 2019)

Leveraging Multi-ethnic Evidence for Mapping Complex Traits in Minority Populations: An Empirical Bayes Approach Marc A. Coram, Sophie I. Candille, Qing.

Genome-Wide Association Studies Identify Multiple Genetic Loci Influencing Eyebrow Color Variation in Europeans Fuduan Peng, Gu Zhu, Pirro G. Hysi, Ryan.

Ursodeoxycholic Acid and Diets Higher in Fat Prevent Gallbladder Stones During Weight Loss: A Meta-analysis of Randomized Controlled Trials Caroline.

Presentation transcript:

Volume 151, Issue 2, Pages 351-363.e28 (August 2016) Four Susceptibility Loci for Gallstone Disease Identified in a Meta-analysis of Genome- Wide Association Studies Amit D. Joshi, Charlotte Andersson, Stephan Buch, Stefan Stender, Raymond Noordam, Lu-Chen Weng, Peter E. Weeke, Paul L. Auer, Bernhard Boehm, Constance Chen, Hyon Choi, Gary Curhan, Joshua C. Denny, Immaculata De Vivo, John D. Eicher, David Ellinghaus, Aaron R. Folsom, Charles Fuchs, Manish Gala, Jeffrey Haessler, Albert Hofman, Frank Hu, David J. Hunter, Harry L.A. Janssen, Jae H. Kang, Charles Kooperberg, Peter Kraft, Wolfgang Kratzer, Wolfgang Lieb, Pamela L. Lutsey, Sarwa Darwish Murad, Børge G. Nordestgaard, Louis R. Pasquale, Alex P. Reiner, Paul M. Ridker, Eric Rimm, Lynda M. Rose, Christian M. Shaffer, Clemens Schafmayer, Rulla M. Tamimi, André G. Uitterlinden, Uwe Völker, Henry Völzke, Yoshiyuki Wakabayashi, Janey L. Wiggs, Jun Zhu, Dan M. Roden, Bruno H. Stricker, Weihong Tang, Alexander Teumer, Jochen Hampe, Anne Tybjærg-Hansen, Daniel I. Chasman, Andrew T. Chan, Andrew D. Johnson Gastroenterology Volume 151, Issue 2, Pages 351-363.e28 (August 2016) DOI: 10.1053/j.gastro.2016.04.007 Copyright © 2016 AGA Institute Terms and Conditions

Figure 1 Manhattan plot of the results of genome-wide meta-analysis of gallstone disease in 10 studies. The plot shows –log10-transformed P values for all SNPs. The red horizontal line represents a P value of 5 × 10-8. The blue horizontal line represents a P value of 1 × 10-5. Gastroenterology 2016 151, 351-363.e28DOI: (10.1053/j.gastro.2016.04.007) Copyright © 2016 AGA Institute Terms and Conditions

Figure 2 Forest plots of meta-analyses of genome-wide significant SNPs in each of the discovery and replication data sets. (A) Fixed-effects meta-analysis: rs1260326. (B) Random-effects meta-analysis: rs11887534. (C) Fixed-effects meta-analysis: rs4245791. (D) Fixed-effects meta-analysis: rs9843304. (E) Random-effects meta-analysis: rs6471717. (F) Fixed-effects meta-analysis: rs2547231. Gastroenterology 2016 151, 351-363.e28DOI: (10.1053/j.gastro.2016.04.007) Copyright © 2016 AGA Institute Terms and Conditions

Figure 3 The possible role of novel susceptibility loci in gallstone formation. Gastroenterology 2016 151, 351-363.e28DOI: (10.1053/j.gastro.2016.04.007) Copyright © 2016 AGA Institute Terms and Conditions

Supplementary Figure 1 Flow chart of study cohorts and methods in the discovery and replication stages. GCTA, Genome-wide complex trait analysis; LD, linkage disequilibrium. Gastroenterology 2016 151, 351-363.e28DOI: (10.1053/j.gastro.2016.04.007) Copyright © 2016 AGA Institute Terms and Conditions

Supplementary Figure 2 Quantile-Quantile plot of gallstone disease GWAS meta-analysis. Gastroenterology 2016 151, 351-363.e28DOI: (10.1053/j.gastro.2016.04.007) Copyright © 2016 AGA Institute Terms and Conditions

Supplementary Figure 3 Regional association plots for discovered loci in GWAS meta-analysis. (A) ABCG8 locus, (B) CYP7A1 locus, (C) GCKR locus, (D) TM4SF4 locus, and (E) SULT2A1 locus. Gastroenterology 2016 151, 351-363.e28DOI: (10.1053/j.gastro.2016.04.007) Copyright © 2016 AGA Institute Terms and Conditions

Supplementary Figure 4 Receiver operator characteristic plots in replication studies. (A) Kiel study (total), (B) women in the Kiel study, (C) men in the Kiel study, (D) NHS replication study, and (E) HPFS replication study. Gastroenterology 2016 151, 351-363.e28DOI: (10.1053/j.gastro.2016.04.007) Copyright © 2016 AGA Institute Terms and Conditions

Supplementary Figure 5 RNA sequencing results from gallbladder and liver from chronic gallstones case and normal gallbladders. Comparison of reads per kilobase of transcript per million (RPKM) values for expressed genes in chronic gallstone gallbladder vs chronic gallstone liver (left panel) and chronic gallstone gallbladder vs normal (nongallstones) gallbladder. The point corresponding to TM4SF4 expression is indicated. The following genes were excluded from the plots because of their high RPKM values: MTRNR2L8, ALB, and APOA2. Gastroenterology 2016 151, 351-363.e28DOI: (10.1053/j.gastro.2016.04.007) Copyright © 2016 AGA Institute Terms and Conditions