{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T02:22:31Z","timestamp":1780626151497,"version":"3.54.1"},"reference-count":46,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,1,2]],"date-time":"2017-01-02T00:00:00Z","timestamp":1483315200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"National Institutes of Health-National Heart, Lung, and Blood Institute"},{"name":"Parker B Francis Foundation"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>There have been a number of candidate gene association studies of cancer cachexia\u2010related traits, but no genome\u2010wide association study (GWAS) has been published to date. Cachexia presents in patients with a number of complex traits, including both cancer and COPD. The objective of the current investigation was to search for a shared genetic aetiology for change in body mass index (\u0394BMI) among cancer and COPD by using GWAS data in the Framingham Heart Study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A linear mixed effects model accounting for age, sex, and change in smoking status was used to calculate \u0394BMI in participants over 40\u2009years of age with three consecutive BMI time points (<jats:italic>n<\/jats:italic>\u2009=\u20094162). Four GWAS of \u0394BMI using generalized estimating equations were performed among 1085 participants with a cancer diagnosis, 204 with gastrointestinal (GI) cancer, 112 with lung cancer, and 237 with COPD to test for association with 418\u2009365 single\u2010nucleotide polymorphisms (SNPs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Two SNPs reached a level of genome\u2010wide significance (<jats:italic>P<\/jats:italic>\u2009&lt;\u20095\u2009\u00d7\u200910<jats:sup>\u22128<\/jats:sup>) with \u0394BMI: (i) rs41526344 within the <jats:italic>CNTN4<\/jats:italic> gene, among COPD cases (<jats:italic>\u03b2<\/jats:italic>\u2009=\u20090.13, <jats:italic>P<\/jats:italic>\u2009=\u20094.3\u2009\u00d7\u200910<jats:sup>\u22128<\/jats:sup>); and (ii) rs4751240 in the gene Dedicator of Cytokinesis 1 (<jats:italic>DOCK1<\/jats:italic>) among GI cancer cases (<jats:italic>\u03b2<\/jats:italic>\u2009=\u20090.10, <jats:italic>P<\/jats:italic>\u2009=\u20091.9\u2009\u00d7\u200910<jats:sup>\u22128<\/jats:sup>). The <jats:italic>DOCK1<\/jats:italic> SNP association replicated in the \u0394BMI GWAS among COPD cases (<jats:italic>\u03b2<\/jats:italic><jats:sub>meta\u2010analyis<\/jats:sub>\u2009=\u20090.10, <jats:italic>P<\/jats:italic><jats:sub>meta\u2010analyis<\/jats:sub>\u2009=\u20099.3\u2009\u00d7\u200910<jats:sup>\u221210<\/jats:sup>). The <jats:italic>DOCK1<\/jats:italic> gene codes for the dedicator of cytokinesis 1 protein, which has a role in myoblast fusion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In sum, one statistically significant common variant in the <jats:italic>DOCK1<\/jats:italic> gene was associated with \u0394BMI in GI cancer and COPD cases providing support for at least partially shared aetiology of \u0394BMI in complex diseases.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12171","type":"journal-article","created":{"date-parts":[[2017,1,3]],"date-time":"2017-01-03T02:26:50Z","timestamp":1483410410000},"page":"428-436","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Body mass index change in gastrointestinal cancer and chronic obstructive pulmonary disease is associated with Dedicator of Cytokinesis 1"],"prefix":"10.1002","volume":"8","author":[{"given":"Merry\u2010Lynn Noelle","family":"McDonald","sequence":"first","affiliation":[{"name":"Channing Division of Network Medicine, Brigham and Women's Hospital Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sungho","family":"Won","sequence":"additional","affiliation":[{"name":"Department of Public Health Science Seoul National University  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Mattheisen","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Centre for integrative Sequencing (iSEQ) Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Castaldi","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine, Brigham and Women's Hospital Harvard Medical School  Boston MA USA"},{"name":"Division of Primary Care and Internal Medicine, Brigham and Women's Hospital Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael H.","family":"Cho","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine, Brigham and Women's Hospital Harvard Medical School  Boston MA USA"},{"name":"Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Rutten","sequence":"additional","affiliation":[{"name":"CIRO+ Centre of Expertise for Chronic Organ Failure  Horn The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Hardin","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine, Brigham and Women's Hospital Harvard Medical School  Boston MA USA"},{"name":"Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai\u2010Ki","family":"Yip","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Harvard School of Public Health  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen I.","family":"Rennard","sequence":"additional","affiliation":[{"name":"Department of Medicine Nebraska Medical Center  Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Lomas","sequence":"additional","affiliation":[{"name":"UCL Respiratory, Division of Medicine University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emiel F.M.","family":"Wouters","sequence":"additional","affiliation":[{"name":"CIRO+ Centre of Expertise for Chronic Organ Failure  Horn The Netherlands"},{"name":"Department of Respiratory Medicine Maastricht University Medical Center Maastricht  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvar","family":"Agusti","sequence":"additional","affiliation":[{"name":"Thorax Institute, Hospital Clinic\u2010IDIBAPS, CIBERES University of Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Casaburi","sequence":"additional","affiliation":[{"name":"Rehabilitation Clinical Trials Center, Los Angeles Biomedical Research Institute Harbor\u2010UCLA Medical Center  Torrance CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph P.","family":"Lange","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Harvard School of Public Health  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"O'Connor","sequence":"additional","affiliation":[{"name":"The National Heart, Lung, and Blood Institute's Framingham Heart Study  Framingham MA USA"},{"name":"Section of 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