Linkage and related analyses of barrett’s esophagus and its associated adenocarcinomas

Xiangqing Sun, Robert Elston, Gary W. Falk, William M. Grady, Ashley Faulx, Sumeet K. Mittal, Marcia Canto, Nicholas J. Shaheen, Jean S. Wang, Prasad G. Iyer, Julian A. Abrams, Joseph E. Willis, Kishore Guda, Sanford Markowitz, Jill S. Barnholtz-Sloan, Apoorva Chandar, Wendy Brock, Amitabh Chak

Research output: Contribution to journalArticle

Abstract

Background Familial aggregation and segregation analysis studies have provided evidence of a genetic basis for esophageal adenocarcinoma (EAC) and its premalignant precursor, Barrett’s esophagus (BE). We aim to demonstrate the utility of linkage analysis to identify the genomic regions that might contain the genetic variants that predispose individuals to this complex trait (BE and EAC). Methods We genotyped 144 individuals in 42 multiplex pedigrees chosen from 1000 singly ascertained BE/EAC pedigrees, and performed both model-based and model-free linkage analyses, using S.A.G.E. and other software. Segregation models were fitted, from the data on both the 42 pedigrees and the 1000 pedigrees, to determine parameters for performing model-based linkage analysis. Model-based and model-free linkage analyses were conducted in two sets of pedigrees: the 42 pedigrees and a subset of 18 pedigrees with female affected members that are expected to be more genetically homogeneous. Genome-wide associations were also tested in these families. Results Linkage analyses on the 42 pedigrees identified several regions consistently suggestive of linkage by different linkage analysis methods on chromosomes 2q31, 12q23, and 4p14. A linkage on 15q26 is the only consistent linkage region identified in the 18 female-affected pedigrees, in which the linkage signal is higher than in the 42 pedigrees. Other tentative linkage signals are also reported. Conclusion Our linkage study of BE/EAC pedigrees identified linkage regions on chromosomes 2, 4, 12, and 15, with some reported associations located within our linkage peaks. Our linkage results can help prioritize association tests to delineate the genetic determinants underlying susceptibility to BE and EAC.

Original languageEnglish (US)
Pages (from-to)407-419
Number of pages13
JournalMolecular Genetics and Genomic Medicine
Volume4
Issue number4
DOIs
StatePublished - Jul 1 2016

Fingerprint

Barrett Esophagus
Pedigree
Adenocarcinoma
Chromosomes, Human, Pair 4
Chromosomes, Human, Pair 2
Software
Chromosomes
Genome

Keywords

  • Barrett’s esophagus
  • Esophageal adenocarcinoma
  • Familial
  • Genetics
  • Linkage

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Sun, X., Elston, R., Falk, G. W., Grady, W. M., Faulx, A., Mittal, S. K., ... Chak, A. (2016). Linkage and related analyses of barrett’s esophagus and its associated adenocarcinomas. Molecular Genetics and Genomic Medicine, 4(4), 407-419. https://doi.org/10.1002/mgg3.211

Linkage and related analyses of barrett’s esophagus and its associated adenocarcinomas. / Sun, Xiangqing; Elston, Robert; Falk, Gary W.; Grady, William M.; Faulx, Ashley; Mittal, Sumeet K.; Canto, Marcia; Shaheen, Nicholas J.; Wang, Jean S.; Iyer, Prasad G.; Abrams, Julian A.; Willis, Joseph E.; Guda, Kishore; Markowitz, Sanford; Barnholtz-Sloan, Jill S.; Chandar, Apoorva; Brock, Wendy; Chak, Amitabh.

In: Molecular Genetics and Genomic Medicine, Vol. 4, No. 4, 01.07.2016, p. 407-419.

Research output: Contribution to journalArticle

Sun, X, Elston, R, Falk, GW, Grady, WM, Faulx, A, Mittal, SK, Canto, M, Shaheen, NJ, Wang, JS, Iyer, PG, Abrams, JA, Willis, JE, Guda, K, Markowitz, S, Barnholtz-Sloan, JS, Chandar, A, Brock, W & Chak, A 2016, 'Linkage and related analyses of barrett’s esophagus and its associated adenocarcinomas', Molecular Genetics and Genomic Medicine, vol. 4, no. 4, pp. 407-419. https://doi.org/10.1002/mgg3.211
Sun, Xiangqing ; Elston, Robert ; Falk, Gary W. ; Grady, William M. ; Faulx, Ashley ; Mittal, Sumeet K. ; Canto, Marcia ; Shaheen, Nicholas J. ; Wang, Jean S. ; Iyer, Prasad G. ; Abrams, Julian A. ; Willis, Joseph E. ; Guda, Kishore ; Markowitz, Sanford ; Barnholtz-Sloan, Jill S. ; Chandar, Apoorva ; Brock, Wendy ; Chak, Amitabh. / Linkage and related analyses of barrett’s esophagus and its associated adenocarcinomas. In: Molecular Genetics and Genomic Medicine. 2016 ; Vol. 4, No. 4. pp. 407-419.
@article{9061d7ad48c74c5fbaef945f676548e6,
title = "Linkage and related analyses of barrett’s esophagus and its associated adenocarcinomas",
abstract = "Background Familial aggregation and segregation analysis studies have provided evidence of a genetic basis for esophageal adenocarcinoma (EAC) and its premalignant precursor, Barrett’s esophagus (BE). We aim to demonstrate the utility of linkage analysis to identify the genomic regions that might contain the genetic variants that predispose individuals to this complex trait (BE and EAC). Methods We genotyped 144 individuals in 42 multiplex pedigrees chosen from 1000 singly ascertained BE/EAC pedigrees, and performed both model-based and model-free linkage analyses, using S.A.G.E. and other software. Segregation models were fitted, from the data on both the 42 pedigrees and the 1000 pedigrees, to determine parameters for performing model-based linkage analysis. Model-based and model-free linkage analyses were conducted in two sets of pedigrees: the 42 pedigrees and a subset of 18 pedigrees with female affected members that are expected to be more genetically homogeneous. Genome-wide associations were also tested in these families. Results Linkage analyses on the 42 pedigrees identified several regions consistently suggestive of linkage by different linkage analysis methods on chromosomes 2q31, 12q23, and 4p14. A linkage on 15q26 is the only consistent linkage region identified in the 18 female-affected pedigrees, in which the linkage signal is higher than in the 42 pedigrees. Other tentative linkage signals are also reported. Conclusion Our linkage study of BE/EAC pedigrees identified linkage regions on chromosomes 2, 4, 12, and 15, with some reported associations located within our linkage peaks. Our linkage results can help prioritize association tests to delineate the genetic determinants underlying susceptibility to BE and EAC.",
keywords = "Barrett’s esophagus, Esophageal adenocarcinoma, Familial, Genetics, Linkage",
author = "Xiangqing Sun and Robert Elston and Falk, {Gary W.} and Grady, {William M.} and Ashley Faulx and Mittal, {Sumeet K.} and Marcia Canto and Shaheen, {Nicholas J.} and Wang, {Jean S.} and Iyer, {Prasad G.} and Abrams, {Julian A.} and Willis, {Joseph E.} and Kishore Guda and Sanford Markowitz and Barnholtz-Sloan, {Jill S.} and Apoorva Chandar and Wendy Brock and Amitabh Chak",
year = "2016",
month = "7",
day = "1",
doi = "10.1002/mgg3.211",
language = "English (US)",
volume = "4",
pages = "407--419",
journal = "Molecular genetics & genomic medicine",
issn = "2324-9269",
publisher = "John Wiley and Sons Inc.",
number = "4",

}

TY - JOUR

T1 - Linkage and related analyses of barrett’s esophagus and its associated adenocarcinomas

AU - Sun, Xiangqing

AU - Elston, Robert

AU - Falk, Gary W.

AU - Grady, William M.

AU - Faulx, Ashley

AU - Mittal, Sumeet K.

AU - Canto, Marcia

AU - Shaheen, Nicholas J.

AU - Wang, Jean S.

AU - Iyer, Prasad G.

AU - Abrams, Julian A.

AU - Willis, Joseph E.

AU - Guda, Kishore

AU - Markowitz, Sanford

AU - Barnholtz-Sloan, Jill S.

AU - Chandar, Apoorva

AU - Brock, Wendy

AU - Chak, Amitabh

PY - 2016/7/1

Y1 - 2016/7/1

N2 - Background Familial aggregation and segregation analysis studies have provided evidence of a genetic basis for esophageal adenocarcinoma (EAC) and its premalignant precursor, Barrett’s esophagus (BE). We aim to demonstrate the utility of linkage analysis to identify the genomic regions that might contain the genetic variants that predispose individuals to this complex trait (BE and EAC). Methods We genotyped 144 individuals in 42 multiplex pedigrees chosen from 1000 singly ascertained BE/EAC pedigrees, and performed both model-based and model-free linkage analyses, using S.A.G.E. and other software. Segregation models were fitted, from the data on both the 42 pedigrees and the 1000 pedigrees, to determine parameters for performing model-based linkage analysis. Model-based and model-free linkage analyses were conducted in two sets of pedigrees: the 42 pedigrees and a subset of 18 pedigrees with female affected members that are expected to be more genetically homogeneous. Genome-wide associations were also tested in these families. Results Linkage analyses on the 42 pedigrees identified several regions consistently suggestive of linkage by different linkage analysis methods on chromosomes 2q31, 12q23, and 4p14. A linkage on 15q26 is the only consistent linkage region identified in the 18 female-affected pedigrees, in which the linkage signal is higher than in the 42 pedigrees. Other tentative linkage signals are also reported. Conclusion Our linkage study of BE/EAC pedigrees identified linkage regions on chromosomes 2, 4, 12, and 15, with some reported associations located within our linkage peaks. Our linkage results can help prioritize association tests to delineate the genetic determinants underlying susceptibility to BE and EAC.

AB - Background Familial aggregation and segregation analysis studies have provided evidence of a genetic basis for esophageal adenocarcinoma (EAC) and its premalignant precursor, Barrett’s esophagus (BE). We aim to demonstrate the utility of linkage analysis to identify the genomic regions that might contain the genetic variants that predispose individuals to this complex trait (BE and EAC). Methods We genotyped 144 individuals in 42 multiplex pedigrees chosen from 1000 singly ascertained BE/EAC pedigrees, and performed both model-based and model-free linkage analyses, using S.A.G.E. and other software. Segregation models were fitted, from the data on both the 42 pedigrees and the 1000 pedigrees, to determine parameters for performing model-based linkage analysis. Model-based and model-free linkage analyses were conducted in two sets of pedigrees: the 42 pedigrees and a subset of 18 pedigrees with female affected members that are expected to be more genetically homogeneous. Genome-wide associations were also tested in these families. Results Linkage analyses on the 42 pedigrees identified several regions consistently suggestive of linkage by different linkage analysis methods on chromosomes 2q31, 12q23, and 4p14. A linkage on 15q26 is the only consistent linkage region identified in the 18 female-affected pedigrees, in which the linkage signal is higher than in the 42 pedigrees. Other tentative linkage signals are also reported. Conclusion Our linkage study of BE/EAC pedigrees identified linkage regions on chromosomes 2, 4, 12, and 15, with some reported associations located within our linkage peaks. Our linkage results can help prioritize association tests to delineate the genetic determinants underlying susceptibility to BE and EAC.

KW - Barrett’s esophagus

KW - Esophageal adenocarcinoma

KW - Familial

KW - Genetics

KW - Linkage

UR - http://www.scopus.com/inward/record.url?scp=85028717244&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85028717244&partnerID=8YFLogxK

U2 - 10.1002/mgg3.211

DO - 10.1002/mgg3.211

M3 - Article

AN - SCOPUS:85028717244

VL - 4

SP - 407

EP - 419

JO - Molecular genetics & genomic medicine

JF - Molecular genetics & genomic medicine

SN - 2324-9269

IS - 4

ER -