Effects of vitamin D-related gene polymorphisms on attempted suicide

Abstract

Objective Emerging evidence suggests that vitamin D might protect from attempted suicide. The study aimed to investigate the associations between single-nucleotide polymorphisms (SNPs) related to vitamin D levels identified in a large genome-wide association study and attempted suicide in rural China.Methods This 1:1 matched case-control study included altogether 510 suicide attempters and 510 community controls. Genotypes of four target SNPs (DHCR7-rs12785878, CYP2R1-rs10741657, GC-rs2282679, and CYP24A1-rs6013897) were determined, and a genetic risk score (GRS) was constructed to evaluate the combined effect of them. Demographic and psychological information was acquired through face-to-face interviews. ResultsThe A allele of CYP24A1-rs6013897 was significantly associated with attempted suicide (OR = 1.27, 95% CI, 1.03-1.58, P = 0.029), even after adjusting for demographic and psychological confounders (adjusted OR = 1.53, 95% CI, 1.01-2.30, P = 0.043). The GRS analyses revealed a significantly higher risk of attempted suicide with a greater number of low vitamin D alleles (adjusted OR = 1.33, 95% CI, 1.13-1.58, P < 0.001). Subgroup analyses stratified by sex indicated that the genetic associations were only significant among males with adjusted ORs of 3.77 (95% CI, 1.56-9.10) for the A allele of rs6013897 and 2.04 (95% CI, 1.32-3.17) for GRS. ConclusionsOur findings identity CYP24A1-rs6013897 as a potential biomarker for attempted suicide and indicate that a genetic predisposition to lower vitamin D levels may contribute to attempted suicide. It suggests the possibility that vitamin D may have the preventive potential for attempted suicide.

Vitamin D and suicidality: a Chinese early adolescent cohort and Mendelian randomization study

“…One case-control study constructed a genetic risk score (GRS) using four vitamin D-related gene polymorphisms (namely, DHCR7-rs12785878, CYP2R1-rs10741657, GC-rs2282679 and CYP24A1-rs6013897). GRS analysis showed a higher risk of attempted suicide with a greater number of low vitamin D alleles in men but not in women (Wei et al, 2021), indicating a sexspecific relationship. Additionally, the relationship between vitamin D and other mental problems was reported to be sex-specific (Hinata et al, 2023;Wang et al, 2022).…”

“…GRS analysis showed a higher risk of attempted suicide with a greater number of low vitamin D alleles in men but not in women (Wei et al. , 2021 ), indicating a sex-specific relationship. Additionally, the relationship between vitamin D and other mental problems was reported to be sex-specific (Hinata et al.…”

The association between vitamin D serum levels, supplementation, and suicide attempts and intentional self-harm

“…Emerging evidence suggests a possible correlation between low vitamin D levels and depression [4]. Vitamin D receptors are located in areas of the brain involved in developing depression, including the hippocampus and hypothalamus [5,6]. Adjuvant treatment of depression with vitamin D supplementation has been recommended [9].…”

“…A growing body of evidence has identified associations between suicidal behavior [3,[6][7][8][9][10][11][12][13] or depressive symptoms [14][15][16][17][18][19][20][21] and low levels of serum 25-hydroxyvitamin D (serum Vitamin D). In a case-control study of 495 service members who had been deployed and later died by suicide, those with seasonally-adjusted Vitamin D serum levels [ ]) less than 15.5 ng/mL had the highest risk of a suicide attempt [3].…”

Vitamin D in Depression: A Potential Bioactive Agent to Reduce Suicide and Suicide Attempt Risk

“…Polymorphisms in the VDR gene can alter its expression in several cells and tissues, including the brain [ 19 , 112 , 113 , 114 ]. Moreover, polymorphisms in this gene can alter the VDR’s function and reduce or enhance the expression of other genes induced by vitamin D [ 115 ].…”