ORIGINAL ARTICLESEvidence of association between brain-derived neurotrophic factor gene and bipolar disorderLiu, Lixianga; Foroud, Tatianaa; Xuei, Xiaolinga; Berrettini, Wadeb; Byerley, Williamc; Coryell, Williame; El-Mallakh, Riff; Gershon, Elliot S.g; Kelsoe, John R.d; Lawson, William B.i; MacKinnon, Dean F.j; McInnis, Melvinl; McMahon, Francis J.k; Murphy, Dennis L.k; Rice, Johnm; Scheftner, Williamh; Zandi, Peter P.j; Lohoff, Falk W.b; Niculescu, Alexander B.a; Meyer, Eric T.a; Edenberg, Howard J.a; Nurnberger, John I. Jra Author Information aIndiana University, Indianapolis, Indiana bUniversity of Pennsylvania, Philadelphia, Pennsylvania cUniversity of California Irvine, Irvine dUniversity of California San Diego, La Jolla, California eUniversity of Iowa, Iowa City, Iowa fUniversity of Louisville, Louisville, Kentucky gUniversity of Chicago hRush University Medical Center, Chicago, Illinois iHoward University, Washington, DC jThe Johns Hopkins Hospital, Baltimore kNational Institute of Mental Health, National Institute of Health, Bethesda, Maryland lUniversity of Michigan, Ann Arbor, Michigan mWashington University St Louis, St Louis, Missouri, USA Correspondence to Dr Tatiana Foroud, PhD, Department of Medical and Molecular Genetics, Indiana University School of Medicine, Health Information and Translational Sciences HS 4000, 410 West 10th Street, Indianapolis, IN 46202-3002, USA Tel: +1 317 278 1291; fax: +1 317 278 1100; e-mail: [email protected] Received 15 June 2007 Revised 16 December 2007 Accepted 6 February 2008 Psychiatric Genetics: December 2008 - Volume 18 - Issue 6 - p 267-274 doi: 10.1097/YPG.0b013e3283060f59 Buy Metrics Abstract Objective Brain-derived neurotrophic factor (BDNF) plays an important role in the survival, differentiation, and outgrowth of select peripheral and central neurons throughout adulthood. Growing evidence suggests that BDNF is involved in the pathophysiology of mood disorders. Methods Ten single nucleotide polymorphisms (SNPs) across the BDNF gene were genotyped in a sample of 1749 Caucasian Americans from 250 multiplex bipolar families. Family-based association analysis was used with three hierarchical bipolar disorder models to test for an association between SNPs in BDNF and the risk of bipolar disorder. In addition, an exploratory analysis was performed to test for an association of the SNPs in BDNF and the phenotypes of rapid cycling and episode frequency. Results Evidence of association (P<0.05) was found with several of the SNPs using multiple models of bipolar disorder; one of these SNPs also showed evidence of association (P<0.05) with rapid cycling. Conclusion These results provide further evidence that variation in BDNF affects the risk for bipolar disorder. © 2008 Lippincott Williams & Wilkins, Inc.