Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
Nonsynonymous Variation in NKPD1 Increases Depressive Symptoms in European Populations. / Amin, Najaf; Belonogova, Nadezhda M.; Jovanova, Olivera и др.
в: Biological Psychiatry, Том 81, № 8, 15.04.2017, стр. 702-707.Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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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.
N1 - Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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