Genome wide association study identifies variants in NBEA associated with migraine in bipolar disorder

Kaya K Jacobsen; Caroline M Nievergelt; Tetyana Zayats; Tiffany A Greenwood; Verneri Anttila; Hagop S Akiskal; BiGS Consortium; IHG Consortium; Jan Haavik; Ole Bernt Fasmer; John R Kelsoe; Stefan Johansson; Ketil J Oedegaard

doi:10.1016/j.jad.2014.10.004

Genome wide association study identifies variants in NBEA associated with migraine in bipolar disorder

J Affect Disord. 2015 Feb 1:172:453-61. doi: 10.1016/j.jad.2014.10.004. Epub 2014 Oct 12.

Collaborators

John R Kelsoe, Tiffany A Greenwood, Caroline M Nievergelt, Rebecca McKinney, Paul D Shilling, Erin N Smith, Nicholas J Schork, Cinnamon S Bloss, John I Nurnberger Jr, Howard J Edenberg, Tatiana Foroud, Daniel L Koller, Elliot S Gershon, Judith A Badner, Chunyu Liu, William A Scheftner, William B Lawson, Evaristus A Nwulia, Maria Hipolito, James Potash, William Coryell, John Rice, William Byerley, Francis J McMahon, Wade H Berrettini, Peter P Zandi, Pamela B Mahon, Melvin G McInnis, Sebastian Zöllner, Peng Zhang, David W Craig, Szabolics Szelinger, Thomas B Barrett, Thomas G Schulze, Juho Wedenoja, Mari A Kaunisto, Kauko Heikkilä, Jaakko Kaprio, Maija Wessman, Mikko Kallela, Markus Färkkilä, Ville Artto, Arpo Aromaa, Johan G Eriksson, Bendik S Winsvold, John-Anker Zwart, Padhraig Gormley, Aarno Palotie, Tobias Kurth, Lynda M Rose, Julie E Buring, Paul M Ridker, Daniel I Chasman, Francesco Bettella, Stacy Steinberg, Hreinn Stefansson, Kari Stefansson, George McMahon, George Davey-Smith, Rainer Malik, Tobias Freilinger, Heinz Erich Wichmann, Martin Dichgans, Bertram Muller-Myhsok, Thomas Meitinger, Boukje de Vries, Gisela Terwindt, Anine H Stam, Rune R Frants, Nadine Pelzer, Claudia M Weller, Ronald Zielman, Michel D Ferrari, Arn M J M van den Maagdenberg, Sarah E Medland, Grant W Montgomery, Nicholas G Martin, Dale R Nyholt, Unda Todt, Guntram Borck, Christian Kubisch, Lydia Quaye, Frances M K Williams, Lynn Cherkas, Markku Koiranen, Anna-Liisa Hartikainen, Anneli Pouta, Marjo-Riitta Jarvelin, M Arfan Ikram, Joyce van den Ende, Andre G Uitterlinden, Albert Hofman, Najaf Amin, Cornelia van Duijn, Terho Lehtimäki, Lannie Ligthart, Jouke-Jan Hottenga, Jacqueline M Vink, Brenda W Penninx, Dorret I Boomsma, Markus Schürks, Finnbogi Jakobsson, Jean Schoenen, Andrew C Heath, Pamela A F Madden, Hartmut Göbel, Axel Heinze, Katja Heinze-Kuhn, Stefan Schreiber, Verneri Anttila, Mark J Daly, Michael Alexander, Olli Raitakari, David P Strachan

Affiliations

¹ KG Jebsen Center for Neurophyciatric research, Department of Biomedicine, University of Bergen, Bergen, Norway; Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway. Electronic address: kja098@biomed.uib.no.
² Department of Psychiatry, University of California, San Diego, USA.
³ KG Jebsen Center for Neurophyciatric research, Department of Biomedicine, University of Bergen, Bergen, Norway; Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
⁴ Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
⁵ Department of Psychiatry, University of California, San Diego, USA; Department of Psychiatry, VA Hospital, San Diego, USA.
⁶ KG Jebsen Center for Neurophyciatric research, Department of Biomedicine, University of Bergen, Bergen, Norway; Division of Psychiatry, Haukeland University Hospital, Bergen, Norway.
⁷ KG Jebsen Center for Neurophyciatric research, Department of Clinical Medicine, University of Bergen, Bergen, Norway; Division of Psychiatry, Haukeland University Hospital, Bergen, Norway.
⁸ KG Jebsen Center for Neurophyciatric research, Department of Biomedicine, University of Bergen, Bergen, Norway; Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Norway.

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.

Keywords: Bipolar disorder; Genetics; Migraine; NBEA; Neurobeachin.

Publication types

Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural

MeSH terms

Adult
Bipolar Disorder / complications*
Bipolar Disorder / epidemiology
Bipolar Disorder / genetics
Carrier Proteins / genetics*
Comorbidity
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Male
Migraine Disorders / epidemiology
Migraine Disorders / etiology
Migraine Disorders / genetics*
Nerve Tissue Proteins / genetics*
Polymorphism, Single Nucleotide*

Substances

Carrier Proteins
NBEA protein, human
Nerve Tissue Proteins

Genome wide association study identifies variants in NBEA associated with migraine in bipolar disorder

Authors

Collaborators

Affiliations

Abstract

Publication types

MeSH terms

Substances

Grants and funding