Genetics Research
rs2439312
Population Frequencies12
African
A 0.23633G 0.76367AA 0.05642AG/GA 0.359818GG 0.583762pop=57,568
African American
A 0.2361G 0.7639AA 0.056205AG/GA 0.359793GG 0.584002pop=55,582
African Others
A 0.2427G 0.7573AA 0.062437AG/GA 0.360524GG 0.577039pop=1,986
Asian
A 0.18392G 0.81608AA 0.044615AG/GA 0.27861GG 0.676775pop=17,214
East Asian
A 0.15264G 0.84736AA 0.026519AG/GA 0.252236GG 0.721246pop=12,972
European
A 0.215234G 0.784766AA 0.04644AG/GA 0.337588GG 0.615972pop=601,894
Latin American 1
A 0.1809G 0.8191AA 0.033171AG/GA 0.295482GG 0.671347pop=9,828
Latin American 2
A 0.11606G 0.88394AA 0.014909AG/GA 0.202306GG 0.782786pop=23,074
Other
A 0.21401G 0.78599AA 0.051588AG/GA 0.32484GG 0.623572pop=31,868
Other Asian
A 0.2796G 0.7204AA 0.099953AG/GA 0.359264GG 0.540783pop=4,242
South Asian
A 0.331G 0.669AA 0.120804AG/GA 0.420416GG 0.458781pop=8,758
Studies6
Unread Studies6 ▼
1
Schizophrenia is a debilitating neuropsychiatric disorder affecting approximately 1% of the global population. Unfortunately, antipsychotic treatment is ineffective in 50% of patients. The complex, heterogeneous and multifactorial nature of antipsychotic response presents a challenge with respect to elucidating the underlying mechanisms. Although genetic, neuroimaging, and clinical studies of antipsychotic response have shown much progress and potential, clinically actionable findings remain incredibly limited. This has hindered the progress toward more personalised treatment approaches, highlighting the necessity of implementing larger cohorts and more integrated approaches in antipsychotic treatment response studies. Genetic and brain structural variation has been widely implicated in antipsychotic response, and there is emerging evidence for a role of childhood trauma in differential treatment outcomes. Although imaging genetics and geneenvironment interaction (GxE) studies have begun to disentangle the underlying relationships between these variables, studies of this nature in antipsychotic response remain scarce. This study aimed to investigate the interplay between genetics, brain structure, childhood trauma, and antipsychotic response, using an integrative approach. This was done with a cohort of 103 first-episode schizophrenia patients treated with a long-acting injectable antipsychotic. Data was available for genome-wide variants, baseline regional brain volumes, childhood trauma severity, and treatment response. Candidate genes previously associated with
2
Context Previous genome-wide association studies have shown that single-nucleotide polymorphism (SNP) rs2439302 in chromosome 8p12 is significantly associated with papillary thyroid carcinoma (PTC) risk and dysregulated NRG1 expression. The underlying mechanisms remain to be discovered. Objective To evaluate the expression of NRG1 isoforms, candidate functional variants, and potential genes downstream of NRG1 in thyroid tissue. Methods Quantitative reverse transcription polymerase chain reaction was applied for gene expression analysis. SNaPshot assay, haplotype, and computer analyses were performed to evaluate candidate functional variants. Other functional assays [chromatin immunoprecipitation (ChIP) assay, luciferase assay, small interfering RNA knockdown, and RNA sequencing] were performed. Results Three NRG1 isoforms (NM_004495, NM_013958, and NM_001160008) tested were highly expressed in thyroid tissue. The expression levels of the three isoforms were significantly correlated with the genotypes of rs2439302. A DNA block of ~32 kb containing the risk G allele of rs2439302 was revealed, harboring multiple candidate functional variants. ChIP assay for active chromatin markers indicated at least nine regions in the DNA block showing strong H3Kme1 and H3K27Ac signals in thyroid tissue. Luciferase reporter assays revealed differential allelic activities associated with seven SNPs. Knocking down NRG1 in primary thyroid cells revealed downstream or interacting genes related to NRG1. Conclusions Our data suggest a role for transcriptional regulation of NRG1 in the predisposition to PTC.
3
… In this study, the significant SNP rs2439312 was strongly associated with T2D (P = 7.00E-6) (Murea et al., 2011) and was highly associated with NRG1 in monocytes (P < E-26) by eQTL …
4
The large volume of GWAS data poses great computational challenges for analyzing genetic interactions associated with common human diseases. We propose a computational …
5
Schizophrenia (SCZ) is highly heritable (up to 80%), but finding vulnerability genes for SCZ is very difficult. The findings from genome-wide association studies do not …
6
African-Americans (AAs) with diabetes have high incidence rates of end-stage renal disease (ESRD) with associated high mortality. Genetic factors modulating the risk of …
Curated Studies0 ▼
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