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Linkage disequilibrium mapping of a chromosome 15q25-26 major depression linkage region and sequencing of NTRK3

Verma, Ranjana, Holmans, Peter Alan, Knowles, James A., Grover, Deepak, Evgrafov, Oleg V., Crowe, Raymond R., Scheftner, William A., Weissman, Myrna M., DePaulo, J. Raymond, Potash, James B. and Levinson, Douglas F. 2008. Linkage disequilibrium mapping of a chromosome 15q25-26 major depression linkage region and sequencing of NTRK3. Biological psychiatry 63 (12) , pp. 1185-1189. 10.1016/j.biopsych.2008.02.005

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Abstract

BACKGROUND: We reported genome-wide significant linkage on chromosome 15q25.3-26.2 to recurrent early-onset major depressive disorder (MDD-RE). Here we present initial linkage-disequilibrium (LD) fine mapping of this signal and sequence analysis of NTRK3 (neurotrophic receptor kinase-3), a biologically plausible candidate gene. METHODS: In 300 pedigrees informative for family-based association, 1195 individuals were genotyped for 795 single nucleotide polymorphism (SNPs). We resequenced 21 exons and 7 highly conserved NTRK3 regions in 176 MDD-RE cases to test for an excess of rare functional variants and, 176 controls for case-control analysis of common variants. RESULTS: LD mapping showed nominally significant association in NTRK3, FLJ12484, RHCG, DKFZp547K1113, VPS33B, SV2B, SLCO3A1, RGMA, and MCTP2 with MDD-RE. In NTRK3, five SNPs had nominally significant p values (.035-.001). Sequence analysis revealed 35 variants (24 novel, including 9 rare exonic); the number of rare variants did not exceed chance expectation. Case-control analysis of 13 common variants showed modest nominal association of MDD-RE with rs4887379, rs6496463, and rs3825882 (p = .008, .048, and .034), which were in partial LD with four of five associated SNPs from the family-based experiment. CONCLUSIONS: Common variants in NTRK3 or other genes identified might play a role in MDD-RE. However, much larger studies are required for full evaluation of this region.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > R Medicine (General)
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords: Association; major depression; neurotrophin NTRK3; tag SNPs; TRKC
Publisher: Elsevier
ISSN: 0006-3223
Last Modified: 02 May 2019 12:33
URI: http://orca.cf.ac.uk/id/eprint/23819

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