PMID- 12161822 OWN - NLM STAT- MEDLINE DCOM- 20021011 LR - 20220309 IS - 0002-9297 (Print) IS - 1537-6605 (Electronic) IS - 0002-9297 (Linking) VI - 71 IP - 3 DP - 2002 Sep TI - The brain-derived neurotrophic factor gene confers susceptibility to bipolar disorder: evidence from a family-based association study. PG - 651-5 AB - Bipolar disorder (BP) is a severe psychiatric disease, with a strong genetic component, that affects 1% of the population worldwide and is characterized by recurrent episodes of mania and depression. Brain-derived neurotrophic factor (BDNF) has been implicated in the pathogenesis of mood disorders, and the aim of the present study was to test for the presence of linkage disequilibrium between two polymorphisms in the BDNF gene and BP in 283 nuclear families. Family-based association test (FBAT) results for the dinucleotide repeat (GT)(N) polymorphism at position -1040 bp showed that allele A3 was preferentially transmitted to the affected individuals (Z=2.035 and P=.042). FBAT results for the val66met SNP showed a significant association for allele G (Z=3.415 and P=.00064). Transmission/disequilibrium test (TDT) haplotype analysis showed a significant result for the 3-G allele combination (P=.000394), suggesting that a DNA variant in the vicinity of the BDNF locus confers susceptibility to BP. Given that there is no direct evidence that either of the polymorphisms we examined alters function, it is unlikely that the actual risk-conferring allele is from these two sites. Rather, the causative site is likely nearby and in linkage disequilibrium with the 3-G haplotype that we have identified. FAU - Neves-Pereira, Maria AU - Neves-Pereira M AD - Neurogenetics Section, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ontario, M5T 1R8, Canada. FAU - Mundo, Emanuela AU - Mundo E FAU - Muglia, Pierandrea AU - Muglia P FAU - King, Nicole AU - King N FAU - Macciardi, Fabio AU - Macciardi F FAU - Kennedy, James L AU - Kennedy JL LA - eng GR - MH59561/MH/NIMH NIH HHS/United States GR - MH59585/MH/NIMH NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. DEP - 20020802 PL - United States TA - Am J Hum Genet JT - American journal of human genetics JID - 0370475 RN - 0 (Brain-Derived Neurotrophic Factor) SB - IM MH - Adult MH - Age of Onset MH - Bipolar Disorder/*genetics MH - Brain-Derived Neurotrophic Factor/*genetics MH - Female MH - Gene Frequency MH - *Genetic Predisposition to Disease MH - Haplotypes/genetics MH - Humans MH - Linkage Disequilibrium/genetics MH - Male MH - Polymorphism, Genetic/*genetics MH - Polymorphism, Single Nucleotide/genetics PMC - PMC379201 EDAT- 2002/08/06 10:00 MHDA- 2002/10/12 04:00 PMCR- 2003/03/01 CRDT- 2002/08/06 10:00 PHST- 2002/03/22 00:00 [received] PHST- 2002/06/11 00:00 [accepted] PHST- 2002/08/06 10:00 [pubmed] PHST- 2002/10/12 04:00 [medline] PHST- 2002/08/06 10:00 [entrez] PHST- 2003/03/01 00:00 [pmc-release] AID - S0002-9297(07)60346-2 [pii] AID - 023922 [pii] AID - 10.1086/342288 [doi] PST - ppublish SO - Am J Hum Genet. 2002 Sep;71(3):651-5. doi: 10.1086/342288. Epub 2002 Aug 2.