The NCAM1 gene set is linked to depressive symptoms and their brain structural correlates in healthy individuals

Abstract

Depressive symptoms exist on a continuum, the far end of which is found in depressive disorders. Utilizing the continuous spectrum of depressive symptoms may therefore contribute to the understanding of the biological underpinnings of depression. Gene set enrichment analysis (GSEA) is an important tool for the identification of gene groups linked to complex traits, and was applied in the present study on genome-wide association study (GWAS) data of depression scores and their brain-level structural correlates in healthy young individuals. On symptom level (i.e. depression scores), robust enrichment was identified for two gene sets: NCAM1 Interactions and Collagen Formation. Depression scores were also associated with decreased fractional anisotropy (FA) - a brain white matter property - within the forceps minor and the left superior temporal longitudinal fasciculus. Within each of these tracts, mean FA value of depression score-associated voxels was used as a phenotype in a subsequent GSEA. The NCAM1 Interactions gene set was significantly enriched in these tracts. By linking the NCAM1 Interactions gene set to depression scores and their structural brain correlates in healthy participants, the current study contributes to the understanding of the molecular underpinnings of depressive symptomatology.

GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal effect of schizophrenia liability

“…NCAM1 is located in the NCAM1-TTC12-ANKK1-DRD2 gene cluster, which is related to neurogenesis and dopaminergic neurotransmission. This gene cluster has been associated with smoking, alcohol use, and illicit drug use 12,33–35 and has been implicated in psychiatric disorders, such as schizophrenia and mood disorders 36,37 .…”

siRNA‐mediated NCAM1 gene silencing suppresses oxidative stress in pre‐eclampsia by inhibiting the p38MAPK signaling pathway

“…In hypertensive families, genetic variance in NCAM1 benefits to the thickness of left ventricular wall . NCAM1 gene set contributes to the depressive symptoms . Furthermore, single nucleotide polymorphisms within NCAM1 confer differential risk to schizophrenia and bipolar disorder .…”

“…27 NCAM1 gene set contributes to the depressive symptoms. 28 Furthermore, single nucleotide polymorphisms within NCAM1 confer differential risk to schizophrenia and bipolar disorder. 29 PE remains a pregnancy-specific complication that characterized by proteinuria and hypertension.…”

Genome-wide association analysis of lifetime cannabis use (N=184,765) identifies new risk loci, genetic overlap with mental health, and a causal influence of schizophrenia on cannabis use

“…NCAM1 is located in the NCAM1-TTC12-ANKK1-DRD2 gene cluster, which is related to neurogenesis and dopaminergic neurotransmission. This gene cluster has been associated with smoking, alcohol use, and illicit drug use [11][12][13][14] and has been implicated in psychiatric disorders, such as schizophrenia and mood disorders [15,16].…”

“…We used existing GWAS summary statistics from the ICC, based on data from 35,297 individuals of European ancestry from 16 cohorts from Northern America, Europe, and Australia [5]. The overall sample included 55.5% females and the age ranged between 16…”