MAD1L1 and TSNARE gene polymorphisms are associated with schizophrenia susceptibility in the Han Chinese population

Abstract

Background Schizophrenia (SCZ) is a severe mental illness with high heritability. This study aimed to explore the correlation between MAD1L1, TSNARE polymorphisms and SCZ susceptibility. Methods A total of 493 SCZ patients and 493 healthy controls were included. The genotypes of MAD1L1 and TSNARE polymorphisms were identified by Agena MassARRAY platform. Odds ratio (OR) and 95% confidence intervals (CIs) were tested via logistic regression analysis in multiple genetic models and different subgroups. Results We observed that AG genotype of rs1107592, AG genotype of rs4976976, and CA genotype of rs67756423 decreased the susceptibility to SCZ (p < 0.05). Age stratification analysis showed that the TC genotype of rs12666575, AG genotype of rs1107592, and AG genotype of rs4976976 decreased the risk of SCZ individuals older than 36 years (p < 0.05). In addition, the AG and AA genotype of rs4976976, the CA genotype of rs67756423 were associated with a lower risk of SCZ in males (p < 0.05). In females, the TT genotype of rs12666575 in recessive model, the AG and AA-AG genotype of rs1107592 in heterozygote and dominant model, could reduce the susceptibility to SCZ (p < 0.05). However, no significant association was found after Bonferroni correction. Conclusions Our results suggest that MAD1L1 and TSNARE genetic polymorphisms exert a protective role in the risk of SCZ. These findings provide evidence that MAD1L1 and TSNARE may serve as potential biomarkers of SCZ. However, a replication experiment in a cohort with large sample size are required to confirm our findings. Trial registration Not applicable.

Personality traits as mediators in the association between SIRT1 rs12415800 polymorphism and depressive symptoms among Chinese college students

“…This protective effect may be attributed to heterozygote advantage (28), a phenomenon in genetics where individuals carrying two different alleles for a particular gene have an advantage over those carrying two copies of the same allele. For instance, MAD1L1 (rs1107592) and TSNARE (rs4976976) heterozygotes showed a decreased risk of schizophrenia (29). Furthermore, variants of genes like SLC6A4 and ANK3 have also been associated with a higher risk of depression or bipolar disorder when present in two copies, but not when present in only one copy (30,31), suggesting that heterozygosity for such variants may confer protection against depression.…”

“…This protective effect can be attributed to the heterozygote advantage, which is a genetic phenomenon where individuals carrying two different alleles for a particular gene have an advantage over those carrying two copies of the same allele (28,32). This advantage has been observed in other genes as well, such as MAD1L1 (rs1107592) and TSNARE (rs4976976) heterozygotes who have a decreased risk of schizophrenia (29), and Ank3+/− heterozygous mice which exhibited similar behavioral alterations of reduced anxiety and increased motivation for reward when compared to wild-type Ank3+/+ mice (33). While the concept of heterozygote advantage is still an active area of research and debate in genetics, and its role in mental disorders is not yet fully established, our findings suggest that the SIRT1 gene may play a protective role in depressive symptoms.…”

DNA methylation as a potential mediator of the association between prenatal tobacco and alcohol exposure and child neurodevelopment in a South African birth cohort

“…Mitotic arrest deficient 1 like 1 ( MAD1L1) is a key regulatory gene of the cell cycle. It has been implicated in the etiology of neuropsychiatric disorders such as SZ and BPD in several genome-wide association studies (GWAS) and candidate gene studies, including one study which found altered levels of expression of MAD1L1 in human neural progenitor cells [ 76 – 78 ]. The biological mechanisms of both SZ and BPD are linked to changes in the mesolimbic reward pathway and high levels of MAD1L1 expression have been found in brain regions such as the ventral tegmental area [ 79 ].…”

DNA Methylation as a Potential Mediator of the Association Between Prenatal Tobacco and Alcohol Exposure and Child Neurodevelopment in a South African Birth Cohort

“…Mitotic arrest deficient 1 like 1 (MAD1L1) is a key regulatory gene of the cell cycle. It has been implicated in the etiology of neurodevelopmental disorders such as SZ and BPD in several genome-wide association studies (GWAS) and candidate gene studies, including one study which found altered levels of expression of MAD1L1 in human neural progenitor cells [69][70][71] . The biological mechanisms of both SZ and BPD are linked to changes in the mesolimbic reward pathway and high levels of MAD1L1 expression have been found in brain regions such as the ventral tegmental area 72 .…”