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. 2008 Jun 15;63(12):1185-9.
doi: 10.1016/j.biopsych.2008.02.005. Epub 2008 Mar 25.

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

Ranjana Verma  1 , Peter Holmans, James A Knowles, Deepak Grover, Oleg V Evgrafov, Raymond R Crowe, William A Scheftner, Myrna M Weissman, J Raymond DePaulo Jr, James B Potash, Douglas F Levinson
Affiliations

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

Ranjana Verma et al. Biol Psychiatry. .

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.

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Figures

Figure
Figure. Genomic organization and allelic association results for the NTRK3 gene
The upper panel shows the exonic structure of the NTRK3 gene while the middle panel depicts the distribution of 47 common variants (MAF > 0.05) analyzed in the family-based (blue) and case-control (pink) association studies. The lower panel shows the allelic association –log p-values obtained through TRANSMIT and Fisher’s exact test statistics. The associated SNPs (p < 0.05) are marked in bold and underlined.
See this image and copyright information in PMC

References

    1. Holmans P, Zubenko GS, Crowe RR, DePaulo JR, Jr, Scheftner WA, Weissman MM, et al. Genomewide significant linkage to recurrent, early-onset major depressive disorder on chromosome 15q. Am J Hum Genet. 2004;74:1154–1167. - PMC - PubMed
    1. Holmans P, Weissman MM, Zubenko GS, Scheftner WA, Crowe RR, DePaulo JR, Jr, et al. Genetics of recurrent early-onset major depression (GenRED): final genome scan report. Am J Psychiatry. 2007;164:248–258. - PubMed
    1. Levinson DF, Evgrafov OV, Knowles JA, Potash JB, Weissman MM, Scheftner WS, et al. Genetics of recurrent early-onset major depression (GenRED): significant linkage on chromosome 15q25-q26 after fine-mapping with SNP markers. Am J Psychiatry. 2007;164:259–264. - PubMed
    1. Lamballe F, Klein R, Barbacid M. trkC, a new member of the trk family of tyrosine protein kinases, is a receptor for neurotrophin-3. Cell. 1991;66:967–979. - PubMed
    1. Watanabe Y, Gould E, Daniels DC, Cameron H, McEwen BS. Tianeptine attenuates stress-induced morphological changes in the hippocampus. Eur J Pharmacol. 1992;222:157–162. - PubMed

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