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Association of Whole-Genome and NETRIN1 Signaling Pathway–Derived Polygenic Risk Scores for Major Depressive Disorder and White Matter Microstructure in the UK Biobank

Publication ,  Journal Article
Barbu, MC; Zeng, Y; Shen, X; Cox, SR; Clarke, TK; Gibson, J; Adams, MJ; Johnstone, M; Haley, CS; Lawrie, SM; Deary, IJ; Wray, NR; Ripke, S ...
Published in: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
January 1, 2019

Background: Major depressive disorder is a clinically heterogeneous psychiatric disorder with a polygenic architecture. Genome-wide association studies have identified a number of risk-associated variants across the genome and have reported growing evidence of NETRIN1 pathway involvement. Stratifying disease risk by genetic variation within the NETRIN1 pathway may provide important routes for identification of disease mechanisms by focusing on a specific process, excluding heterogeneous risk-associated variation in other pathways. Here, we sought to investigate whether major depressive disorder polygenic risk scores derived from the NETRIN1 signaling pathway (NETRIN1-PRSs) and the whole genome, excluding NETRIN1 pathway genes (genomic-PRSs), were associated with white matter microstructure. Methods: We used two diffusion tensor imaging measures, fractional anisotropy (FA) and mean diffusivity (MD), in the most up-to-date UK Biobank neuroimaging data release (FA: n = 6401; MD: n = 6390). Results: We found significantly lower FA in the superior longitudinal fasciculus (β = −.035, pcorrected =.029) and significantly higher MD in a global measure of thalamic radiations (β =.029, pcorrected =.021), as well as higher MD in the superior (β =.034, pcorrected =.039) and inferior (β =.029, pcorrected =.043) longitudinal fasciculus and in the anterior (β =.025, pcorrected =.046) and superior (β =.027, pcorrected =.043) thalamic radiation associated with NETRIN1-PRS. Genomic-PRS was also associated with lower FA and higher MD in several tracts. Conclusions: Our findings indicate that variation in the NETRIN1 signaling pathway may confer risk for major depressive disorder through effects on a number of white matter tracts.

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Published In

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

DOI

EISSN

2451-9030

ISSN

2451-9022

Publication Date

January 1, 2019

Volume

4

Issue

1

Start / End Page

91 / 100

Related Subject Headings

  • 5203 Clinical and health psychology
  • 5202 Biological psychology
  • 3209 Neurosciences
 

Citation

APA
Chicago
ICMJE
MLA
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Barbu, M. C., Zeng, Y., Shen, X., Cox, S. R., Clarke, T. K., Gibson, J., … Owen, M. J. (2019). Association of Whole-Genome and NETRIN1 Signaling Pathway–Derived Polygenic Risk Scores for Major Depressive Disorder and White Matter Microstructure in the UK Biobank. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 4(1), 91–100. https://doi.org/10.1016/j.bpsc.2018.07.006
Barbu, M. C., Y. Zeng, X. Shen, S. R. Cox, T. K. Clarke, J. Gibson, M. J. Adams, et al. “Association of Whole-Genome and NETRIN1 Signaling Pathway–Derived Polygenic Risk Scores for Major Depressive Disorder and White Matter Microstructure in the UK Biobank.” Biological Psychiatry: Cognitive Neuroscience and Neuroimaging 4, no. 1 (January 1, 2019): 91–100. https://doi.org/10.1016/j.bpsc.2018.07.006.
Barbu MC, Zeng Y, Shen X, Cox SR, Clarke TK, Gibson J, et al. Association of Whole-Genome and NETRIN1 Signaling Pathway–Derived Polygenic Risk Scores for Major Depressive Disorder and White Matter Microstructure in the UK Biobank. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. 2019 Jan 1;4(1):91–100.
Barbu, M. C., et al. “Association of Whole-Genome and NETRIN1 Signaling Pathway–Derived Polygenic Risk Scores for Major Depressive Disorder and White Matter Microstructure in the UK Biobank.” Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, vol. 4, no. 1, Jan. 2019, pp. 91–100. Scopus, doi:10.1016/j.bpsc.2018.07.006.
Barbu MC, Zeng Y, Shen X, Cox SR, Clarke TK, Gibson J, Adams MJ, Johnstone M, Haley CS, Lawrie SM, Deary IJ, Wray NR, Ripke S, Mattheisen M, Trzaskowski M, Byrne EM, Abdellaoui A, Agerbo E, Air TM, Andlauer TFM, Bacanu SA, Bækvad-Hansen M, Beekman ATF, Bigdeli TB, Binder EB, Blackwood DHR, Bryois J, Buttenschøn HN, Bybjerg-Grauholm J, Cai N, Castelao E, Christensen JH, Coleman JRI, Colodro-Conde L, Couvy-Duchesne B, Craddock N, Crawford GE, Davies G, Degenhardt F, Derks EM, Direk N, Dolan CV, Dunn EC, Eley TC, Escott-Price V, Hassan Kiadeh FF, Finucane HK, Forstner AJ, Frank J, Gaspar HA, Gill M, Goes FS, Gordon SD, Grove J, Hall LS, Hansen CS, Hansen TF, Herms S, Hickie IB, Hoffmann P, Homuth G, Horn C, Hottenga JJ, Hougaard DM, Ising M, Jansen R, Jorgenson E, Knowles JA, Kohane IS, Kraft J, Kretzschmar WW, Krogh J, Kutalik Z, Li Y, Lind PA, MacIntyre DJ, MacKinnon DF, Maier RM, Maier W, Marchini J, Mbarek H, McGrath P, McGuffin P, Medland SE, Mehta D, Middeldorp CM, Mihailov E, Milaneschi Y, Milani L, Mondimore FM, Montgomery GW, Mostafavi S, Mullins N, Nauck M, Ng B, Nivard MG, Nyholt DR, O’Reilly PF, Oskarsson H, Owen MJ. Association of Whole-Genome and NETRIN1 Signaling Pathway–Derived Polygenic Risk Scores for Major Depressive Disorder and White Matter Microstructure in the UK Biobank. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. 2019 Jan 1;4(1):91–100.

Published In

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

DOI

EISSN

2451-9030

ISSN

2451-9022

Publication Date

January 1, 2019

Volume

4

Issue

1

Start / End Page

91 / 100

Related Subject Headings

  • 5203 Clinical and health psychology
  • 5202 Biological psychology
  • 3209 Neurosciences