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Chunk #23 — Results

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Genome-wide Association Study Identifies a Regulatory Variant of RGMA Associated With Opioid Dependence in European Americans.
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The expression of six genes previously associated with psychiatric disorders and two potential regulators for RGMA were correlated with that of RGMA in brain tissue samples (n=1301). These genes are GRIN1 (glutamate receptor, ionotropic, N-methyl D-aspartate 1), KCNIP3 (Kv channel interacting protein 3, calsenilin), PTCHD1 (patched domain containing 1), FXYD6 (FXYD domain containing ion transport regulator 6), DLG4 (discs, large homolog 4) and NRG1 (neuregulin 1), as well as two potential regulators (TCF3 and TCF4). GRIN1, FXYD6, NRG1 and DLG4 have been associated with schizophrenia (21-24), KCNIP3 with Alzheimer's disease (25), PTCHD1 with autism (26), and NRG1 with psychosis (27). The E-box (5′-CANNTG-3′) motif of the two potential regulators, TCF3 and TCF4, was found in the promoter region of RGMA, GRIN1 and PTCHD1. We combined normalized expression data (z-scores) of 1301 brain tissue samples to test the pairwise correlation among the six genes. As shown in Supplementary figure 4A, the expressions of GRIN1, KCNIP3, FXYD6, PTCHD1, RGMA, TCF3 and TCF4 were highly inter-correlated. For RGMA, there was a strong positive correlation with GRIN1 (Pearson correlation coefficient r=0.40 and P=7.0×10-50) and KCNIP3 (r=0.38 and P=1.35×10-45) (Supplementary figure 4B), with the latter two also significantly inter-correlated (Supplementary figure 4A: r=0.73 and P=1×10-200).