{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The gamma‐aminobutyric acid receptor rho‐2 subunit, encoded by the GABRR2 gene, is an integral component of GABA receptors that belong to the GABA"}, {"type": "i", "children": [{"type": "t", "text": "C"}]}, {"type": "t", "text": " (or GABA_A/GABA"}, {"type": "i", "children": [{"type": "t", "text": "C"}]}, {"type": "t", "text": ") receptor family. Several human genetic studies have implicated GABRR2 in the modulation of inhibitory neurotransmission that underlies diverse brain functions. For example, in research on autism spectrum disorder, a single‐nucleotide polymorphism within GABRR2 was found to be significantly associated with the condition, suggesting that subtle alterations in GABA"}, {"type": "i", "children": [{"type": "t", "text": "C"}]}, {"type": "t", "text": " receptor composition might contribute to neurodevelopmental risk."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, a meta‐analysis investigating schizophrenia and bipolar disorder identified one of the top single-nucleotide polymorphisms very close to the GABRR2 locus, lending support to the idea that variations in or near this gene may influence susceptibility to major psychiatric disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n There is also evidence from studies of epilepsy that population-specific genetic variation in GABRR2 could contribute to disease predisposition."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In the context of alcohol dependence, family-based association analyses have identified a coding polymorphism (Met430Thr) in GABRR2 with a stronger effect among individuals with earlier onset of the disorder, highlighting the potential importance of GABA"}, {"type": "i", "children": [{"type": "t", "text": "C"}]}, {"type": "t", "text": " receptor modification in addictive behaviors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Furthermore, analyses of transcripts during brain development have shown that among the three rho subunits expressed in brain regions such as the hippocampus and superior colliculus, rho2 (GABRR2) is highly represented, indicating that it may play a crucial role in establishing proper inhibitory signaling during early postnatal maturation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its roles in neurodevelopment and neurotransmission, alterations in GABRR2 expression have been observed in peripheral tissues. For instance, in a genome-wide association study of serum creatinine levels, polymorphisms in a locus harboring GABRR2 provided corroborative evidence for a role of GABA receptors in the regulation of the glomerular basement membrane, linking GABAergic mechanisms to kidney function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Moreover, changes in GABRR2 expression have been detected in peripheral blood following risperidone treatment in first-episode psychosis patients, suggesting that the gene’s regulation might be responsive to antipsychotic therapy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Finally, a recent study in a Chinese Han population has provided evidence that a genetic variant in GABRR2 can modulate performance on measures of general cognitive ability, implying that GABRR2-dependent modulation of inhibitory transmission may impact higher-order cognitive function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these findings support a multifaceted role for GABRR2 in modulating neural inhibition that may influence neurodevelopment, cognitive processes, and susceptibility to a range of neuropsychiatric and even peripheral phenotypes. \n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "D Q Ma, P L Whitehead, M M Menold, et al. 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