Genome wide association study identifies variants in NBEA associated with migraine in bipolar disorder
Kaya K. Jacobsen(Haukeland University Hospital), Caroline M. Nievergelt(University of California San Diego), Tetyana Zayats(Haukeland University Hospital), Tiffany A. Greenwood(University of California San Diego), Verneri Anttila(Broad Institute), Hagop S. Akiskal(University of San Diego), Jan Haavik(Haukeland University Hospital), Ole Bernt Fasmer(Haukeland University Hospital), John R. Kelsoe(University of San Diego), Stefan Johansson(Haukeland University Hospital), Ketil J. Øedegaard(Haukeland University Hospital), John R. Kelsoe(University of San Diego), Tiffany A. Greenwood(University of California San Diego), Caroline M. Nievergelt(University of California San Diego), Rebecca McKinney(University of California San Diego), Paul D. Shilling(University of California San Diego), Erin N. Smith(University of California San Diego), Nicholas J. Schork(Scripps Research Institute), Cinnamon S. Bloss(Scripps Research Institute), John I. Nürnberger(Indiana University – Purdue University Indianapolis), Howard J. Edenberg(Indiana University – Purdue University Indianapolis), Tatiana Foroud(Indiana University – Purdue University Indianapolis), Daniel L. Koller(Indiana University – Purdue University Indianapolis), Elliot S. Gershon(University of Illinois Chicago), Judith A. Badner(University of Illinois Chicago), Chunyu Liu, William A. Scheftner(Rush University Medical Center), William Lawson(Reykjavík University), Evaristus Nwulia(Howard University), Maria Hipolito(Institute for Molecular Medicine Finland), James B. Potash(University of Iowa), William Coryell(University of Iowa), John Rice(University of California San Diego), William Byerley(University of California, San Francisco), Francis J. McMahon(Harvard University), Wade H. Berrettini(University of Bergen), Peter P. Zandi(Johns Hopkins University), Pamela B. Mahon(Harvard University), Melvin G. McInnis(Tampere University), Sebastian Zöllner(University of Michigan), Peng Zhang(University of Michigan), David W. Craig(Translational Genomics Research Institute), Szabolics Szelinger(Translational Genomics Research Institute), Thomas B. Barrett(Tampere University), Thomas G. Schulze(University of Göttingen), Juho Wedenoja(University of Helsinki), Mari Kaunisto(Institute for Molecular Medicine Finland), Kauko Heikkilä(University of Helsinki), Jaakko Kaprio(Institute for Molecular Medicine Finland), Maija Wessman(Institute for Molecular Medicine Finland), Mikko Kallela, Markus Färkkilä, Ville Artto, Arpo Aromaa(University of Oslo), Johan G. Eriksson, Bendik S. Winsvold(University of Bergen), John‐Anker Zwart(deCODE Genetics (Iceland)), Padhraig Gormley(Wellcome Sanger Institute), Aarno Palotie(Institute for Molecular Medicine Finland), Tobias Kurth(Harvard University), Lynda Rose(Harvard University), Julie E. Buring(Harvard University), Paul M. Ridker(Harvard University), Daniel I. Chasman(Harvard University), Francesco Bettella(deCODE Genetics (Iceland)), Stacy Steinberg(deCODE Genetics (Iceland)), Hreinn Stefánsson(deCODE Genetics (Iceland)), Kāri Stefánsson(Leiden University Medical Center), George McMahon(deCODE Genetics (Iceland)), George Davey-Smith(deCODE Genetics (Iceland)), Rainer Malik(Tampere University), Tobias Freilinger(Ludwig-Maximilians-Universität München), Heinz Erich Wichmann(Leiden University Medical Center), Martin Dichgans(Leiden University Medical Center), Bertram Müller‐Myhsok(Tampere University), Thomas Meitinger(University of Bergen), Boukje de Vries(Leiden University Medical Center), Gisela M. Terwindt(Leiden University Medical Center), Anine H Stam(Leiden University Medical Center), Rune R. Frants(Leiden University Medical Center), Nadine Pelzer(Leiden University Medical Center), Claudia M Weller(Leiden University Medical Center), Ronald Zielman(Leiden University Medical Center), Michel D. Ferrari(Leiden University Medical Center), Arn M.J.M. van den Maagdenberg(Harvard University), Sarah E. Medland(QIMR Berghofer Medical Research Institute), Grant W. Montgomery(Tampere University), Nicholas G. Martin(QIMR Berghofer Medical Research Institute), Dale R. Nyholt(QIMR Berghofer Medical Research Institute), Unda Todt(King's College London), Guntram Borck(King's College London), Christian Kubisch(King's College London), Lydia Quaye(Washington University in St. Louis), Frances M. K. Williams(University of Bergen), Lynn Cherkas(Tampere University), Markku Koiranen(Leiden University Medical Center), Anna‐Liisa Hartikainen(deCODE Genetics (Iceland)), Anneli Pouta(Institute for Molecular Medicine Finland), Marjo‐Riitta Järvelin(University of Oulu), M. Arfan Ikram(Institute for Molecular Medicine Finland), Joyce van den Ende(Tampere University), André G. Uitterlinden(Tampere University), Albert Hofman(Tampere University), Najaf Amin(Tampere University), Cornelia M. van Duijn(University of Helsinki), Terho Lehtimäki(Tampere University), Lannie Ligthart(Leiden University Medical Center), Jouke‐Jan Hottenga(University of Helsinki), Jacqueline M. Vink(Essen University Hospital), Brenda W.J.H. Penninx(Essen University Hospital), Dorret I. Boomsma(Essen University Hospital), Markus Schürks, Finnbogi Jakobsson(Reykjavík University), Jean Schoenen(University of Liège), Andrew C. Heath(Washington University in St. Louis), Pamela A. F. Madden(Washington University in St. Louis), Hartmut Göbel(University of Bergen), Axel Heinze(University of Bergen), Katja Heinze‐Kuhn(Leiden University Medical Center), Stefan Schreiber(Haukeland University Hospital), Verneri Anttila(Broad Institute), Mark J. Daly(Institute for Molecular Medicine Finland), Michael P. Alexander(Leiden University Medical Center), Olli T. Raitakari(University of London), David P. Strachan(University of Helsinki)
Cited by 21Open Access
Abstract
BACKGROUND: Migraine is a common comorbidity among individuals with bipolar disorder, but the underlying mechanisms for this co-occurrence are poorly understood. The aim of this study was to investigate the genetic background of bipolar patients with and without migraine. METHODS: We performed a genome-wide association analysis contrasting 460 bipolar migraneurs with 914 bipolar patients without migraine from the Bipolar Genome Study (BiGS). RESULTS: We identified one genome-wide significant association between migraine in bipolar disorder patients and rs1160720, an intronic single nucleotide polymorphism (SNP) in the NBEA gene (P=2.97 × 10(-8), OR: 1.82, 95% CI: 1.47-2.25), although this was not replicated in a smaller sample of 289 migraine cases. LIMITATIONS: Our study is based on self-reported migraine. CONCLUSIONS: NBEA encodes neurobeachin, a scaffolding protein primarily expressed in the brain and involved in trafficking of vesicles containing neurotransmitter receptors. This locus has not previously been implicated in migraine per se. We found no evidence of association in data from the GWAS migraine meta-analysis consortium (n=118,710 participants) suggesting that the association might be specific to migraine co-morbid with bipolar disorder.
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