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. 2018 May 3;8(1):6983.
doi: 10.1038/s41598-018-25529-y.

Gene-based analysis of genes related to neurotrophic pathway suggests association of BDNF and VEGFA with antidepressant treatment-response in depressed patients

Chung-Feng Kao  1 , Yu-Li Liu  2 , Younger W-Y Yu  3 , Albert C Yang  4   5   6   7 , Eugene Lin  8   9 , Po-Hsiu Kuo  10 , Shih-Jen Tsai  11   12   13
Affiliations

Gene-based analysis of genes related to neurotrophic pathway suggests association of BDNF and VEGFA with antidepressant treatment-response in depressed patients

Chung-Feng Kao et al. Sci Rep. .

Abstract

It is well established that brain-derived neurotrophic factor (BDNF) signaling pathway plays a key role in the pathophysiology of major depressive disorder (MDD) and in therapeutic mechanisms of antidepressants. We aim to identify genetic vairiants related to MDD susceptibility and antidepressant therapeutic response by using gene-based association analysis with genes related to the neurotrophic pathway. The present study investigated the role of genetic variants in the 10 neurotrophic-related genes (BDNF, NGFR, NTRK2, MTOR, VEGFA, S100A10, SERPINE1, ARHGAP33, GSK3B, CREB1) in MDD susceptibility through a case-control (455 MDD patients and 2,998 healthy controls) study and in antidepressant efficacy (n = 455). Measures of antidepressant therapeutic efficacy were evaluated using the 21-item Hamilton Rating Scale for Depression. Our single-marker and gene-based analyses with ten genes related to the neurotrophic pathway identified 6 polymorphisms that reached a significant level (p-value < 5.0 × 10-3) in both meta- and mega-analyses in antidepressant therapeutic response. One polymorphism was mapped to BDNF and 5 other polymorphisms were mapped to VEGFA. For case-control association study, we found that all of these reported polymorphisms and genes did not reach a suggestive level. The present study supported a role of BDNF and VEGFA variants in MDD therapeutic response.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Manhattan plot of meta-analysis of selected candidate genes for Remitted (Score).
Figure 2
Figure 2
Manhattan plot of mega-analysis of selected candidate genes for Remitted (Score).
Figure 3
Figure 3
Manhattan plot of meta-analysis of selected candidate genes for Response (%ΔHRSD, continuous).
Figure 4
Figure 4
Manhattan plot of mega-analysis of selected candidate genes for Response (%ΔHRSD, continuous).
See this image and copyright information in PMC

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