Nonsynonymous Variation in NKPD1 Increases Depressive Symptoms in European Populations

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Nonsynonymous Variation in NKPD1 Increases Depressive Symptoms in European Populations. / Amin, Najaf; Belonogova, Nadezhda M.; Jovanova, Olivera et al.

In: Biological Psychiatry, Vol. 81, No. 8, 15.04.2017, p. 702-707.

Research output: Contribution to journal › Article › peer-review

Harvard

Amin, N, Belonogova, NM, Jovanova, O, Brouwer, RWW, van Rooij, JGJ, van den Hout, MCGN, Svishcheva, GR, Kraaij, R, Zorkoltseva, IV, Kirichenko, AV, Hofman, A, Uitterlinden, AG, van IJcken, WFJ, Tiemeier, H, Axenovich, TI & van Duijn, CM 2017, 'Nonsynonymous Variation in NKPD1 Increases Depressive Symptoms in European Populations', Biological Psychiatry, vol. 81, no. 8, pp. 702-707. https://doi.org/10.1016/j.biopsych.2016.08.008

APA

Amin, N., Belonogova, N. M., Jovanova, O., Brouwer, R. W. W., van Rooij, J. G. J., van den Hout, M. C. G. N., Svishcheva, G. R., Kraaij, R., Zorkoltseva, I. V., Kirichenko, A. V., Hofman, A., Uitterlinden, A. G., van IJcken, W. F. J., Tiemeier, H., Axenovich, T. I., & van Duijn, C. M. (2017). Nonsynonymous Variation in NKPD1 Increases Depressive Symptoms in European Populations. Biological Psychiatry, 81(8), 702-707. https://doi.org/10.1016/j.biopsych.2016.08.008

Vancouver

Amin N, Belonogova NM, Jovanova O, Brouwer RWW, van Rooij JGJ, van den Hout MCGN et al. Nonsynonymous Variation in NKPD1 Increases Depressive Symptoms in European Populations. Biological Psychiatry. 2017 Apr 15;81(8):702-707. doi: 10.1016/j.biopsych.2016.08.008

Author

Amin, Najaf ; Belonogova, Nadezhda M. ; Jovanova, Olivera et al. / Nonsynonymous Variation in NKPD1 Increases Depressive Symptoms in European Populations. In: Biological Psychiatry. 2017 ; Vol. 81, No. 8. pp. 702-707.

BibTeX

@article{6e213496413d476798bc4c3b10b9cfce,

title = "Nonsynonymous Variation in NKPD1 Increases Depressive Symptoms in European Populations",

abstract = "Background Despite high heritability, little success was achieved in mapping genetic determinants of depression-related traits by means of genome-wide association studies. Methods To identify genes associated with depressive symptomology, we performed a gene-based association analysis of nonsynonymous variation captured using exome-sequencing and exome-chip genotyping in a genetically isolated population from the Netherlands (n = 1999). Finally, we reproduced our significant findings in an independent population-based cohort (n = 1604). Results We detected significant association of depressive symptoms with a gene NKPD1 (p = 3.7 × 10−08). Nonsynonymous variants in the gene explained 0.9% of sex- and age-adjusted variance of depressive symptoms in the discovery study, which is translated into 3.8% of the total estimated heritability (h2 = 0.24). Significant association of depressive symptoms with NKPD1 was also observed (n = 1604; p = 1.5 × 10−03) in the independent replication sample despite little overlap with the discovery cohort in the set of nonsynonymous genetic variants observed in the NKPD1 gene. Meta-analysis of the discovery and replication studies improved the association signal (p = 1.0 × 10−09). Conclusions Our study suggests that nonsynonymous variation in the gene NKPD1 affects depressive symptoms in the general population. NKPD1 is predicted to be involved in the de novo synthesis of sphingolipids, which have been implicated in the pathogenesis of depression.",

keywords = "CESD, Depressive symptoms, Exome sequencing, Major depression, MDD, NKPD1, European Continental Ancestry Group/genetics, Genome-Wide Association Study, Humans, Middle Aged, Membrane Proteins/genetics, Male, Nucleoside-Triphosphatase/genetics, Depressive Disorder, Major/genetics, Exome, Genetic Variation, Depression/genetics, Netherlands, Nerve Tissue Proteins/genetics, Female, Polymorphism, Single Nucleotide, METAANALYSIS, RARE, CELL-LINES, INDIVIDUALS, SERINE PALMITOYLTRANSFERASE, GENOME-WIDE ASSOCIATION, VARIANTS, MAJOR DEPRESSION, LESCH-NYHAN-DISEASE, SEQUENCING DATA",

author = "Najaf Amin and Belonogova, {Nadezhda M.} and Olivera Jovanova and Brouwer, {Rutger W.W.} and {van Rooij}, {Jeroen G.J.} and {van den Hout}, {Mirjam C.G.N.} and Svishcheva, {Gulnara R.} and Robert Kraaij and Zorkoltseva, {Irina V.} and Kirichenko, {Anatoly V.} and Albert Hofman and Uitterlinden, {Andr{\'e} G.} and {van IJcken}, {Wilfred F.J.} and Henning Tiemeier and Axenovich, {Tatiana I.} and {van Duijn}, {Cornelia M.}",

year = "2017",

month = apr,

day = "15",

doi = "10.1016/j.biopsych.2016.08.008",

language = "English",

volume = "81",

pages = "702--707",

journal = "Biological Psychiatry",

issn = "0006-3223",

publisher = "Elsevier Science Inc.",

number = "8",

}

RIS

TY - JOUR

T1 - Nonsynonymous Variation in NKPD1 Increases Depressive Symptoms in European Populations

AU - Amin, Najaf

AU - Belonogova, Nadezhda M.

AU - Jovanova, Olivera

AU - Brouwer, Rutger W.W.

AU - van Rooij, Jeroen G.J.

AU - van den Hout, Mirjam C.G.N.

AU - Svishcheva, Gulnara R.

AU - Kraaij, Robert

AU - Zorkoltseva, Irina V.

AU - Kirichenko, Anatoly V.

AU - Hofman, Albert

AU - Uitterlinden, André G.

AU - van IJcken, Wilfred F.J.

AU - Tiemeier, Henning

AU - Axenovich, Tatiana I.

AU - van Duijn, Cornelia M.

PY - 2017/4/15

Y1 - 2017/4/15

N2 - Background Despite high heritability, little success was achieved in mapping genetic determinants of depression-related traits by means of genome-wide association studies. Methods To identify genes associated with depressive symptomology, we performed a gene-based association analysis of nonsynonymous variation captured using exome-sequencing and exome-chip genotyping in a genetically isolated population from the Netherlands (n = 1999). Finally, we reproduced our significant findings in an independent population-based cohort (n = 1604). Results We detected significant association of depressive symptoms with a gene NKPD1 (p = 3.7 × 10−08). Nonsynonymous variants in the gene explained 0.9% of sex- and age-adjusted variance of depressive symptoms in the discovery study, which is translated into 3.8% of the total estimated heritability (h2 = 0.24). Significant association of depressive symptoms with NKPD1 was also observed (n = 1604; p = 1.5 × 10−03) in the independent replication sample despite little overlap with the discovery cohort in the set of nonsynonymous genetic variants observed in the NKPD1 gene. Meta-analysis of the discovery and replication studies improved the association signal (p = 1.0 × 10−09). Conclusions Our study suggests that nonsynonymous variation in the gene NKPD1 affects depressive symptoms in the general population. NKPD1 is predicted to be involved in the de novo synthesis of sphingolipids, which have been implicated in the pathogenesis of depression.

AB - Background Despite high heritability, little success was achieved in mapping genetic determinants of depression-related traits by means of genome-wide association studies. Methods To identify genes associated with depressive symptomology, we performed a gene-based association analysis of nonsynonymous variation captured using exome-sequencing and exome-chip genotyping in a genetically isolated population from the Netherlands (n = 1999). Finally, we reproduced our significant findings in an independent population-based cohort (n = 1604). Results We detected significant association of depressive symptoms with a gene NKPD1 (p = 3.7 × 10−08). Nonsynonymous variants in the gene explained 0.9% of sex- and age-adjusted variance of depressive symptoms in the discovery study, which is translated into 3.8% of the total estimated heritability (h2 = 0.24). Significant association of depressive symptoms with NKPD1 was also observed (n = 1604; p = 1.5 × 10−03) in the independent replication sample despite little overlap with the discovery cohort in the set of nonsynonymous genetic variants observed in the NKPD1 gene. Meta-analysis of the discovery and replication studies improved the association signal (p = 1.0 × 10−09). Conclusions Our study suggests that nonsynonymous variation in the gene NKPD1 affects depressive symptoms in the general population. NKPD1 is predicted to be involved in the de novo synthesis of sphingolipids, which have been implicated in the pathogenesis of depression.

KW - CESD

KW - Depressive symptoms

KW - Exome sequencing

KW - Major depression

KW - MDD

KW - NKPD1

KW - European Continental Ancestry Group/genetics

KW - Genome-Wide Association Study

KW - Humans

KW - Middle Aged

KW - Membrane Proteins/genetics

KW - Male

KW - Nucleoside-Triphosphatase/genetics

KW - Depressive Disorder, Major/genetics

KW - Exome

KW - Genetic Variation

KW - Depression/genetics

KW - Netherlands

KW - Nerve Tissue Proteins/genetics

KW - Female

KW - Polymorphism, Single Nucleotide

KW - METAANALYSIS

KW - RARE

KW - CELL-LINES

KW - INDIVIDUALS

KW - SERINE PALMITOYLTRANSFERASE

KW - GENOME-WIDE ASSOCIATION

KW - VARIANTS

KW - MAJOR DEPRESSION

KW - LESCH-NYHAN-DISEASE

KW - SEQUENCING DATA

UR - http://www.scopus.com/inward/record.url?scp=84991225375&partnerID=8YFLogxK

U2 - 10.1016/j.biopsych.2016.08.008

DO - 10.1016/j.biopsych.2016.08.008

M3 - Article

C2 - 27745872

AN - SCOPUS:84991225375

VL - 81

SP - 702

EP - 707

JO - Biological Psychiatry

JF - Biological Psychiatry

SN - 0006-3223

IS - 8

ER -

ID: 10041002