title: Epiregulin (EREG) and human V-ATPase (TCIRG1): genetic variation, ethnicity and pulmonary tuberculosis susceptibility in Guinea-Bissau and The Gambia.
abstract: We analyzed two West African samples (Guinea-Bissau: n=289 cases and 322 controls; The Gambia: n=240 cases and 248 controls) to evaluate single-nucleotide polymorphisms (SNPs) in Epiregulin (EREG) and V-ATPase (T-cell immune regulator 1 (TCIRG1)) using single and multilocus analyses to determine whether previously described associations with pulmonary tuberculosis (PTB) in Vietnamese and Italians would replicate in African populations. We did not detect any significant single locus or haplotype associations in either sample. We also performed exploratory pairwise interaction analyses using Visualization of Statistical Epistasis Networks (ViSEN), a novel method to detect only interactions among multiple variables, to elucidate possible interaction effects between SNPs and demographic factors. Although we found no strong evidence of marginal effects, there were several significant pairwise interactions that were identified in either the Guinea-Bissau or the Gambian samples, two of which replicated across populations. Our results indicate that the effects of EREG and TCIRG1 variants on PTB susceptibility, to the extent that they exist, are dependent on gene-gene interactions in West African populations as detected with ViSEN. In addition, epistatic effects are likely to be influenced by inter- and intra-population differences in genetic or environmental context and/or the mycobacterial lineages causing disease.
authors.affiliation: 1] Center for Human Genetics Research, Vanderbilt University, Nashville, TN, USA [2] Department of Genetics and Institute of Quantitative Biomedical Sciences, Dartmouth College, Hanover, NH, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: White
authors.affiliation: Centro di Ricerca, Ospedale San Pietro Fatebenefratelli, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Tacconelli
authors.affiliation: Department of Genetics and Institute of Quantitative Biomedical Sciences, Dartmouth College, Hanover, NH, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Chen
authors.affiliation: 1] Bandim Health Project, Danish Epidemiology Science Centre and Statens Serum Institute, Bissau, Guinea-Bissau [2] Department of Infectious Diseases, Aarhus University Hospital, Skejby, Denmark [3] Center for Global Health, School of Public Health, Aarhus University, Skejby, Denmark.
authors.forename: C
authors.initials: C
authors.lastname: Wejse
authors.affiliation: 1] Centre for International Health, University of Otago School of Medicine, Dunedin, New Zealand [2] MRC Laboratories, Fajara, The Gambia.
authors.forename: P C
authors.initials: PC
authors.lastname: Hill
authors.affiliation: Bandim Health Project, Danish Epidemiology Science Centre and Statens Serum Institute, Bissau, Guinea-Bissau.
authors.forename: V F
authors.initials: VF
authors.lastname: Gomes
authors.affiliation: 1] Vanderbilt Epidemiology Center, Vanderbilt University, Nashville, TN, USA [2] Institute for Medicine and Public Health, Vanderbilt University, Nashville, TN, USA [3] Center for Human Genetics Research, Vanderbilt University, Nashville, TN, USA [4] Department of Obstetrics and Gynecology, Vanderbilt University, Nashville, TN, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Velez-Edwards
authors.affiliation: Department of Infectious Diseases, Aarhus University Hospital, Skejby, Denmark.
authors.forename: L J
authors.initials: LJ
authors.lastname: Østergaard
authors.affiliation: Department of Genetics and Institute of Quantitative Biomedical Sciences, Dartmouth College, Hanover, NH, USA.
authors.forename: T
authors.initials: T
authors.lastname: Hu
authors.affiliation: Department of Genetics and Institute of Quantitative Biomedical Sciences, Dartmouth College, Hanover, NH, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Moore
authors.affiliation: 1] Centro di Ricerca, Ospedale San Pietro Fatebenefratelli, Rome, Italy [2] Dipartimento di Biomedicina e Prevenzione, Sezione di Genetica, Università di Roma 'Tor Vergata', Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Novelli
authors.affiliation: Dr John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: W K
authors.initials: WK
authors.lastname: Scott
authors.affiliation: Department of Genetics and Institute of Quantitative Biomedical Sciences, Dartmouth College, Hanover, NH, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Williams
authors.affiliation: Centro di Ricerca, Ospedale San Pietro Fatebenefratelli, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Sirugo
mesh_terms: D000328:Adult; D000483:Alleles; D044383:Black People / Q000235:genetics; D066260:Epiregulin / Q000235:genetics*; D004843:Epistasis, Genetic; D005714:Gambia; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D005838:Genotype; D006169:Guinea-Bissau; D006801:Humans; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D014397:Tuberculosis, Pulmonary / Q000208:ethnology / Q000235:genetics*; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics*
chemical_list: D066260:Epiregulin; C472421:TCIRG1 protein, human; D025262:Vacuolar Proton-Translocating ATPases