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Gender-stratified analysis of DLG5 R30Q in 4707 Crohn's disease patients and 4973 controls from 12 Caucasian cohorts
  1. Brian L Browning (b.browning{at}auckland.ac.nz)
  1. The University of Auckland, New Zealand
    1. Murray L Barclay (murray.barclay{at}cdhb.govt.nz)
    1. Christchurch Hospital, New Zealand
      1. Sheila A Bingham (sab{at}mrc-dunn.cam.ac.uk)
      1. University of Cambridge, United Kingdom
        1. Stephan Brand (stephan.brand{at}med.uni-muenchen.de)
        1. University of Munich, Germany
          1. Carsten Buning (carsten.buening{at}charite.de)
          1. Universitatsmedizin Berlin, Germany
            1. Massimo Castro (castro{at}opbg.net)
            1. IRCCS Bambino Gesu Children's Hospital, Italy
              1. Salvatore Cucchiara (salvatore.cucchiara{at}uniroma1.it)
              1. University of Rome La Sapienza, Italy
                1. Bruno Dallapiccola (dallapiccola{at}operapadrepio.it)
                1. IRCCS CSS-Mendel Institute, Italy
                  1. Hazel Drummond (hdrummond{at}ed.ac.uk)
                  1. University of Edinburgh, United Kingdom
                    1. Lynnette R Ferguson (l.ferguson{at}auckland.ac.nz)
                    1. The University of Auckland, New Zealand
                      1. Alessandro Ferraris (a.ferraris{at}css-mendel.it)
                      1. CSS - Mendel Institute, Italy
                        1. Sheila A Fisher (sheila.fisher{at}genetics.kcl.ac.uk)
                        1. Kings College London School of Medicine, United Kingdom
                          1. Richard B Gearry (richard.gearry{at}cdhb.govt.nz)
                          1. Christchurch Hospital, New Zealand
                            1. Jurgen Glas (juergen.glas{at}med.uni-muenchen.de)
                            1. University of Munich, Germany
                              1. Liesbet Henckaerts (liesbet.henckaerts{at}uz.kuleuven.ac.be)
                              1. UZ Gasthuisberg, Belgium
                                1. Claudia Huebner (c.huebner{at}auckland.ac.nz)
                                1. The University of Auckland, New Zealand
                                  1. Daniela Knafelz (knafelz{at}opbg.net)
                                  1. IRCCS Bambino Gesu Children's Hospital, Italy
                                    1. Laszlo Lakatos (lakatos.laszlo{at}vmkorhaz.hu)
                                    1. Csolnoky F. County Hospital, Hungary
                                      1. Peter Laszlo Lakatos (kislakpet{at}yahoo.com)
                                      1. Semmelweis University, Hungary
                                        1. Anna Latiano (a.latiano{at}operapadrepio.it)
                                        1. IRCCS Casa Sollievo della Sofferenza, Italy
                                          1. Xiangdong Liu (xiangdong.liu{at}uhn.on.ca)
                                          1. University of Toronto, Canada
                                            1. Christopher G Mathew (christopher.mathew{at}genetics.kcl.ac.uk)
                                            1. King's College London School of Medicine, United Kingdom
                                              1. Bertram Müller-Myhsok (bmm{at}mpipsykl.mpg.de)
                                              1. Max-Planck-Institut für Psychiatrie, Germany
                                                1. William G Newman (william.newman{at}manchester.ac.uk)
                                                1. University of Manchester, United Kingdom
                                                  1. Elaine R Nimmo (enimmo{at}staffmail.ed.ac.uk)
                                                  1. University of Edinburgh, United Kingdom
                                                    1. Colin L Noble (noblecolin{at}hotmail.com)
                                                    1. University of Edinburgh, United Kingdom
                                                      1. Orazio Palmieri (o.palmieri{at}operapadrepio.it)
                                                      1. IRCCS Caso Sollievo della Sofferenza, Italy
                                                        1. Miles Parkes (miles.parkes{at}addenbrookes.nhs.uk)
                                                        1. Addenbrookes Hospital, United Kingdom
                                                          1. Ivonne Petermann (i.petermann{at}auckland.ac.nz)
                                                          1. The University of Auckland, New Zealand
                                                            1. Paul Rutgeerts (paul.rutgeerts{at}uz.kuleuven.ac.be)
                                                            1. UZ Gasthuisberg, Belgium
                                                              1. Jack Satsangi (j.satsangi{at}ed.ac.uk)
                                                              1. University of Edinburgh, United Kingdom
                                                                1. Andrew N Shelling (a.shelling{at}auckland.ac.nz)
                                                                1. University of Auckland, New Zealand
                                                                  1. Katherine A Siminovitch (ksiminovitch{at}mtsinai.on.ca)
                                                                  1. University of Toronto, Canada
                                                                    1. Helga-Paula Torok (helga.toeroek{at}med.uni-muenchen.de)
                                                                    1. University of Munich, Germany
                                                                      1. Mark Tremelling (mark.tremelling{at}addenbrookes.nhs.uk)
                                                                      1. Addenbrookes Hospital, United Kingdom
                                                                        1. Severine Vermeire (severine.vermeire{at}uz.kuleuven.ac.be)
                                                                        1. UZ Gasthuisberg, Belgium
                                                                          1. Rossella Valvano (mr.valvano{at}operapadrepio.it)
                                                                          1. IRCCS Casa Sollievo della Sofferenza, Italy
                                                                            1. Annese Vito (v.annese{at}operapadrepio.it)
                                                                            1. IRCCS Casa Sollievo della Sofferenza, Italy
                                                                              1. Heiko Witt (heiko.witt{at}charite.de)
                                                                              1. Universitatsmedizin Berlin, Germany

                                                                                Abstract

                                                                                Background: DLG5 p.R30Q has been reported to be associated with Crohn’s disease (CD), but this association has not been replicated in most studies. A recent analysis of gender-stratified data from two case-control studies and two population cohorts found an association of DLG5 30Q with increased risk of CD in men, but not in women, and found differences between male and female 30Q population frequencies. Male-female differences in population allele frequencies and male-specific risk could explain the difficulty in replicating the association with CD.

                                                                                Methods: We collected DLG5 R30Q genotype data for CD patients and controls from 11 studies that did not include gender-stratified allele counts in their published reports, and we tested for male-female frequency differences in controls, and for case-control frequency differences in men and in women

                                                                                Results: Our data shows no male-female allele frequency differences in controls. An exact conditional test gives marginal evidence that 30Q is associated with decreased risk of CD in women (p = 0.049, OR 0.87, 95% CI 0.77-1.00). There was also a trend of reduced 30Q frequencies in male CD patients compared to male controls, but this was not significant at the 0.05 level (p = 0.058, OR 0.87, 95% CI 0.74–1.01). When our data are combined with previously published, gender-stratified data, the 30Q allele is associated with decreased risk of CD in women (p = 0.010, OR 0.86, 95% CI 0.76-0.97), but not in men.

                                                                                Conclusion: DLG5 30Q is associated with a small reduction in risk of CD in women.

                                                                                • Crohn's disease
                                                                                • DLG5
                                                                                • R30Q
                                                                                • inflammatory bowel disease
                                                                                • meta-analysis

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