Gene‐level genome‐wide association analysis of suicide attempt, a preliminary study in a psychiatric Mexican population

Abstract

BackgroundEvidence suggests that liability for suicide behavior is heritable; additionally, suicide has been partly related to other psychiatric disorders. Nevertheless, most of the information reported so far address Caucasian and Asian individuals. Hence, our aim was to conduct a gene‐level association study in Mexican psychiatric individuals diagnosed with suicide attempt.MethodsWe recruited 192 individuals from two clinical centers in Mexico. All participants were born in Mexico and had Mexican parents and grandparents. Direct genotyping was performed using the commercial platform Infinium PsychArray BeadChip. A p‐value lower than 1e‐05 was considered as gene‐level significant and a p‐value lower than 1e‐04 was considered as gene‐level nominal significant.ResultsOur analyses showed that SCARA5 was associated to suicide intent at a gene‐level with statistical significance (p‐value = 1.12e‐6). Other genes were nominally associated with suicide attempt: GHSR (p‐value = 0.0004), RGS10 (p‐value = 5.13e‐5), and STK33 (p‐value = 3.62e‐5). Regarding gene variant analyses, the SNPs with a statistical association (p > .05) were rs561361616, rs1537577, rs11198999 for RGS10, and rs11041981, rs11041993, rs11041994, rs11041995, rs11041997, rs10840083, rs10769918 for STK33. For these genes, previous studies have associated SCARA5 with depression, GHSR with alcohol dependence and depression, and RGS10 with schizophrenia and depression. To date, STK33 has not been associated with any psychiatric disorder.ConclusionOur outcomes revealed that SCARA5, GHSR, RGS10 and STK33 could be considered as risk biomarkers for suicide attempt behavior in our Mexican psychiatric sample. We recommend to perform larger scale analyses to have conclusive results.

Genetic contributions to suicidal thoughts and behaviors

“…The lack of ancestral diversity in psychiatric genetics to date limits the identification and generalizability of potential genetic risk factors and can contribute to health disparities (Kang & Ruderfer, 2020 ). Smaller studies of STBs have been conducted in cohorts of African American (Levey et al, 2019 ; N = 3238 cases with SA), Mexican (González-Castro et al, 2019b ; N = 37 cases with SA), Peruvian (Shen et al, 2020 , N = 522 cases with SI) and East Asian (Otsuka et al, 2019 ; N = 746 suicide cases) ancestries. Notably, polygenic analyses from the suicide GWAS in Japan were successful, in which a significant SNP-based genetic correlation of suicide was observed between two independent Japanese cohorts of suicide death (Otsuka et al, 2019 ).…”

Investigation of de novo mutations in a schizophrenia case-parent trio by induced pluripotent stem cell-based in vitro disease modeling: convergence of schizophrenia- and autism-related cellular phenotypes

“…Wnt3A, Wnt6, Wnt7B, and Wnt10A both play an important role in brain and neuronal crest development. SCARA5, the most downregulated gene in the proband-derived NPCs, is associated with suicidal behavior in a recently published genome-wide association study [ 39 ]. Synapsin 3 (SYN3), another top downregulated DE gene, has been implicated in the regulation of hippocampal neurogenesis [ 40 ] and associated with SZ in genetic studies [ 41 ].…”

Investigation of de novo mutations in a schizophrenia case-parent trio by induced pluripotent stem cell based in vitro disease-modeling: Convergence of schizophrenia and autism-related cellular phenotypes

“…Wnt3A, Wnt6, Wnt7B and Wnt10A both play an important role in brain and neuronal crest development. SCARA5, the most downregulated gene in the proband-derived NPCs is associated with suicidal behavior in a recently published genome-wide association study (40). Synapsin 3 (SYN3), another top downregulated DE gene, has been implicated in the regulation of hippocampal neurogenesis (41), and associated with SZ in genetic studies (42).…”