Julio Licinio1, Chuanhui Dong, Ma-Li Wong. 1. Center on Pharmacogenomics, Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, Florida 33136, USA. licinio@miami.edu
Abstract
CONTEXT: Variations in the brain-derived neurotrophic factor gene (BDNF) have been associated with psychiatric disorders. Deep sequencing of the BDNF gene may identify new variations and bring further insight into psychiatric genetics. OBJECTIVE: To better characterize sequence variability in the BDNF gene by resequencing a genomic DNA region of 22 kilobases that contained all BDNF exons and their flanking regions. DESIGN: Case-control study. SETTING: University of California, Los Angeles, and University of Miami. PARTICIPANTS: Two hundred sixty-four controls and 272 Mexican Americans with major depressive disorder (MDD) from Los Angeles who were assessed by the same bilingual clinical research team. MAIN OUTCOME MEASURES: Identification of novel genetic polymorphisms in the BDNF gene and assessment of their frequencies and associations with MDD or antidepressant response. RESULTS: We identified 83 novel single-nucleotide polymorphisms (SNPs): 30 in untranslated regions, 4 in coding sequences, 37 in introns, and 12 in upstream regions; 3 of 4 rare novel coding SNPs were nonsynonymous. Association analyses of patients with MDD and controls showed that 6 SNPs were associated with MDD (rs12273539, rs11030103, rs6265, rs28722151, rs41282918, and rs11030101) and 2 haplotypes in different blocks (one including Val66, another near exon VIIIh) were significantly associated with MDD. One recently reported 5' untranslated region SNP, rs61888800, was associated with antidepressant response after adjusting for age, sex, medication, and baseline score on the 21-item Hamilton Depression Rating Scale. CONCLUSIONS: Our data support the concept that extensive resequencing of key candidate genes can lead to the discovery of substantial numbers of new variants. Further studies using larger independent samples are needed to confirm the association of the rs61888800 SNP with antidepressant response. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00265291.
RCT Entities:
CONTEXT: Variations in the brain-derived neurotrophic factor gene (BDNF) have been associated with psychiatric disorders. Deep sequencing of the BDNF gene may identify new variations and bring further insight into psychiatric genetics. OBJECTIVE: To better characterize sequence variability in the BDNF gene by resequencing a genomic DNA region of 22 kilobases that contained all BDNF exons and their flanking regions. DESIGN: Case-control study. SETTING: University of California, Los Angeles, and University of Miami. PARTICIPANTS: Two hundred sixty-four controls and 272 Mexican Americans with major depressive disorder (MDD) from Los Angeles who were assessed by the same bilingual clinical research team. MAIN OUTCOME MEASURES: Identification of novel genetic polymorphisms in the BDNF gene and assessment of their frequencies and associations with MDD or antidepressant response. RESULTS: We identified 83 novel single-nucleotide polymorphisms (SNPs): 30 in untranslated regions, 4 in coding sequences, 37 in introns, and 12 in upstream regions; 3 of 4 rare novel coding SNPs were nonsynonymous. Association analyses of patients with MDD and controls showed that 6 SNPs were associated with MDD (rs12273539, rs11030103, rs6265, rs28722151, rs41282918, and rs11030101) and 2 haplotypes in different blocks (one including Val66, another near exon VIIIh) were significantly associated with MDD. One recently reported 5' untranslated region SNP, rs61888800, was associated with antidepressant response after adjusting for age, sex, medication, and baseline score on the 21-item Hamilton Depression Rating Scale. CONCLUSIONS: Our data support the concept that extensive resequencing of key candidate genes can lead to the discovery of substantial numbers of new variants. Further studies using larger independent samples are needed to confirm the association of the rs61888800 SNP with antidepressant response. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00265291.
Authors: Jane Winantea; My Ngo Hoang; Stefanie Ohlraun; Marcella Rietschel; Sven Cichon; Peter Propping; Markus M Nöthen; Jan Freudenberg; Yun Freudenberg-Hua Journal: Eur J Hum Genet Date: 2006-05-31 Impact factor: 4.246
Authors: Michael F Egan; Masami Kojima; Joseph H Callicott; Terry E Goldberg; Bhaskar S Kolachana; Alessandro Bertolino; Eugene Zaitsev; Bert Gold; David Goldman; Michael Dean; Bai Lu; Daniel R Weinberger Journal: Cell Date: 2003-01-24 Impact factor: 41.582
Authors: Andrew J Saykin; Li Shen; Tatiana M Foroud; Steven G Potkin; Shanker Swaminathan; Sungeun Kim; Shannon L Risacher; Kwangsik Nho; Matthew J Huentelman; David W Craig; Paul M Thompson; Jason L Stein; Jason H Moore; Lindsay A Farrer; Robert C Green; Lars Bertram; Clifford R Jack; Michael W Weiner Journal: Alzheimers Dement Date: 2010-05 Impact factor: 21.566
Authors: George S Alexopoulos; Charles E Glatt; Matthew J Hoptman; Dora Kanellopoulos; Christopher F Murphy; Robert E Kelly; Sarah S Morimoto; Kelvin O Lim; Faith M Gunning Journal: J Affect Disord Date: 2010-03-25 Impact factor: 4.839
Authors: Francesca Cirulli; Andreas Reif; Sabine Herterich; K Peter Lesch; Alessandra Berry; Nadia Francia; Luigi Aloe; Christina S Barr; Stephen J Suomi; Enrico Alleva Journal: Psychoneuroendocrinology Date: 2010-12-09 Impact factor: 4.905
Authors: Rong Jiang; Beverly H Brummett; Michael A Babyak; Ilene C Siegler; Redford B Williams Journal: J Psychiatr Res Date: 2012-11-08 Impact factor: 4.791