Association of mineralocorticoid receptor gene (NR3C2) hypermethylation in adult males with aggressive behavior.

Aggressive behavior may have adaptive value under some environmental conditions. However, when it is extreme or improper, it may also lead to maladaptive results, seriously threatening human and social well-being. Aggressive behavior is a multifactorial disease, and the etiology is largely unknown. The stress-related hypothalamic-pituitary-adrenal (HPA) axis is a crucial system in the stress response that has emerged as a potential mechanism of aggressive behavior. The NR3C2 gene is an important regulator of the HPA axis: it is involved in regulating HPA axis activity and behavioral adaptation to stressors. Moreover, the epigenetic mechanism of DNA methylation has been suggested to mediate the development of aggressive behavior. However, the association between NR3C2 methylation and aggressive behavior has not been studied. In the present study, we assessed NR3C2 methylation (including three regions: promoter P1, exon 1α, and the sequence downstream of exon 1α) in peripheral blood DNA of adult males with aggressive behavior (n = 106) and healthy controls (n = 104). We found the NR3C2 gene to be associated with aggressive behavior, with hypermethylation detected in the entire aggressive behavior group as well as in the robbery subgroup compared to controls. In addition, analysis of methylation at 75 CpG sites revealed that some important CpG sites are associated with aggressive behavior. Our results suggest that HPA axis-related gene NR3C2 methylation is associated with aggressive behavior. These results lend support for using NR3C2 DNA methylation as a potential biomarker of aggressive behavior.

Retraction "Methylation of the MAOA promoter is associated with schizophrenia".

[This retracts the article DOI: 10.21037/atm-20-4481.].

Methylation of the MAOA promoter is associated with schizophrenia.

BACKGROUND: Earlier studies have shown that patients with schizophrenia have abnormalities in DNA methylation. Monoamine oxidase A (MAOA) has been extensively studied due to its biological role in neurological function. However, the relationship between the DNA methylation of the MAOA gene and schizophrenia is unclear. This study aims to elucidate the relationship between the methylation of the MAOA gene promoter and schizophrenia. METHODS: There were 151 individuals with schizophrenia (104 males and 47 females), which were diagnosed according to DSM-V, the DNA of peripheral blood of all samples was extracted and chemically modified with bisulfite. The promoter region of MAOA gene was sequenced by Methylation Target Technical Method (MethylTargetTM), and 247 controls (204 males and 43 females) included in the study. MAOA gene promoter methylation was compared between the case and control groups. Meanwhile, we measured DNA methylation in two regions of MAOA (MAOA-2 and MAOA-3). RESULTS: In the male schizophrenia group (BM) and the male control group (DM), MAOA-2 and MAOA-3 methylation were positively associated with schizophrenia. In the female schizophrenia group (BF) and the female control group (DF), MAOA-2 methylation was associated with schizophrenia. CONCLUSIONS: Although the role of gene methylation in the development of schizophrenia is still unclear, our findings suggest that DNA methylation of MAOA may contribute to the onset of schizophrenia.

Massively parallel sequencing of STRs using a 29-plex panel reveals stutter sequence characteristics.

Massively parallel sequencing of forensic STRs simultaneously provides length-based genotypes and core repeat sequences as well as flanking sequence variations. Here, we report primer sequences and concentrations of a next-generation sequencing (NGS)-based in-house panel covering 28 autosomal STR loci (CSF1PO, D1GATA113, D1S1627, D1S1656, D1S1677, D2S441, D2S1776, D3S3053, D5S818, D6S474, D6S1017, D6S1043, D8S1179, D9S2157, D10S1435, D11S4463, D13S317, D14S1434, D16S539, D18S51, D18S853, D20S482, D20S1082, D22S1045, FGA, TH01, TPOX, and vWA) and the sex determinant locus Amelogenin. Preliminary evaluation experiments showed that the panel yielded intralocus- and interlocus-balanced sequencing data with a sensitivity as low as 62.5 pg input DNA. A total of 203 individuals from Yunnan Bai population were sequenced with this panel. Comparative forensic genetic analyses showed that sequence-based matching probability of this 29-plex panel reached 2.37 × 10-29 , which was 23 times lower than the length-based data. Compound stutter sequences of eight STRs were compared with parental alleles. For seven loci, repeat motif insertions or deletions occurred in the longest uninterrupted repeat sequences (LUS). However, LUS and non-LUS stutters co-existed in the locus D6S474 with different sequencing depth ratios. These results supplemented our current knowledge of forensic STR stutters, and provided a sound basis for DNA mixture deconvolution.

DNA Methylation Analysis of the NR3C1 Gene in Patients with Schizophrenia.

Schizophrenia is a heterogeneous mental disorder caused by genetic and environmental factors, and epigenetic mechanisms play a vital role in its pathogenesis. Evidence suggests that some psychiatric disorders are linked to methylation of the glucocorticoid receptor gene NR3C1, a key regulator of the hypothalamic-pituitary-adrenal (HPA) axis. However, the contribution of NR3C1 methylation to schizophrenia has not yet been investigated. By applying a case-control approach (N = 128 controls, N = 80 patients), we for the first time examined the methylation state of the NR3C1 gene promoter region and its role in schizophrenia. Using peripheral blood samples, NR3C1 methylation in exons 1D, 1B, 1F, and 1H was assessed via sodium bisulfite treatment combined with the MethylTarget method. NR3C1 methylation at exon 1B was positively associated with schizophrenia in females but not in males. Nonetheless, specific CpG sites in exon 1D, 1B, 1H, and 1F regions were found to be associated with schizophrenia, usually with sex specificity. These results suggest that epigenetic aberrations of NR3C1 are associated with the pathophysiology of schizophrenia, and epigenetic processes possibly mediate psychopathology through effects on HPA axis activity. Correlation analysis between NR3C1 gene methylation and schizophrenia may be helpful for the assessment of forensic psychiatry.