Meta-analysis of GABRB2 polymorphisms and the risk of schizophrenia combined with GWAS data of the Han Chinese population and psychiatric genomics consortium

Abstract

Schizophrenia (SCZ) is a severe psychiatric disorder with evidence of a strong genetic component in the complex etiologies. Some studies indicated that gamma-aminobutyric acid (GABA)A receptor β2 subunit gene (GABRB2) was associated with SCZ. Other studies reported a negative association. Moreover, the results of two previous meta-analyses of GABRB2 with SCZ were inconsistent and the sample sizes were limited. Therefore, an updated meta-analysis combined with genome-wide association study (GWAS) data of the Han Chinese population and Psychiatric Genomics Consortium (PGC) was performed. Available case–control and family-based genetic data were extracted from association studies, and the GWAS data were included. The findings showed no association between six single-nucleotide polymorphisms of GABRB2 (rs6556547, rs1816071, rs1816072, rs194072, rs252944, and rs187269) and SCZ in a total of 51,491 patients and 74,667 controls. The ethnic subgroup analysis revealed no significant association in Asian populations. Since the PGC data of SCZ (SCZ-PGC, 2014) contained 3 studies of Asian populations (1866 patients and 3418 controls), only the data of European samples in SCZ-PGC were used for the meta-analysis of the Caucasian population in the present study. The result still showed no association in the Caucasian population. In conclusion, the present meta-analysis on combined data from GWASs of the Han Chinese population and PGC suggested that GABRB2 polymorphisms might not be associated with SCZ.

Meta-analyses of genome wide association studies in lines of laying hens divergently selected for feather pecking using imputed sequence level genotypes

“…Although we were not able to confirm the aforementioned genes related to GABAergic signaling, we were able to detect 52 intron variants, among them two insertions, with -log10(p) > 5 on GGA13 (8,084,380 -8,135,739 bp), which affect the GABA-receptor subunit GABRB2 (Additional File 2). For GABRB2 as well strong evidence exists to be a causative gene for schizophrenia [43][44][45][46][47][48][49][50] and it seems to be involved in opioid addiction [51]. Iffland et al [6] found the QTL region on GGA1 also associated with FPD, but we were not able to confirm this in our GWAS based on imputed sequence level genotypes.…”

Investigation of candidate genes and mechanisms underlying obesity associated type 2 diabetes mellitus using bioinformatics analysis and screening of small drug molecules

“…Genes such as KCNE5 [ 45 ], SHANK3 [ 46 ], CASQ2 [ 47 ], EDNRA (endothelin receptor type A) [ 48 ], EPHB4 [ 49 ], ALPK3 [ 50 ], WNT11 [ 51 ], IRAK2 [ 52 ], FBN1 [ 53 ], SFRP2 [ 54 ], CLCA2 [ 55 ], NEXN (nexilin F-actin binding protein) [ 56 ], PALLD (palladin, cytoskeletal associated protein) [ 57 ], DAB2 [ 58 ], NRP2 [ 59 ], THBS2 [ 60 ], CSF1R [ 61 ], KCNA2 [ 62 ], CACNA1C [ 63 ], F2R [ 64 ], UCHL1 [ 65 ], CCL18 [ 66 ], ITGB1BP2 [ 67 ] and FMOD (fibromodulin) [ 68 ] were reportedly involved in cardio vascular diseases, but these genes might be key for progression of obesity associated type 2 diabetes mellitus. Hu et al [ 69 ], Liu et al [ 70 ], Eltokhi et al [ 71 ], Cai et al [ 72 ], Pfeiffer et al [ 73 ], Lin et al [ 74 ], Royer-Zemmour et al [ 75 ], Pastor et al [ 76 ], Goodspeed et al [ 77 ], Zhang et al [ 78 ], Rogers et al [ 79 ], Su et al [ 80 ] and Foale et al [ 81 ] reported that NRXN1, CRHR1, SHANK2, PSEN2, CKB (creatine kinase B), CD200R1, SRPX2, PTPRZ1, SLC6A1, GABRB2, KCNA1, ASAH1 and LINGO1 were the genes expressed in progression of neuropsychiatric disorders, but these genes might be involved in advancement of obesity associated type 2 diabetes mellitus. Reports indicate that genes include SPHK2 [ 82 ], NPC1L1 [ 83 ], CNTFR (ciliaryneurotrophic factor receptor) [ 84 ], SLC2A4 [ 85 ], EDA (ectodysplasin A) [ 86 ], TGM2 [ 87 ], GCK (glucokinase) [ 88 ], FASN (fatty acid synthase) [ 89 ], FAP (fibroblast activation protein alpha) [ 90 ], PRNP (prion protein) [ 91 ], LYVE1 [ 92 ], SERPINE1 [ 93 ], TNF (tumor necrosis factor) [ 94 ], FASLG (Fas ligand) [ 95 ...…”

Investigation of Candidate Genes and Mechanisms Underlying Obesity Associated Type 2 Diabetes Mellitus Using Bioinformatics Analysis and Screening of Small Drug Molecules 

“…KCNE5 [45], SHANK3 [46], CASQ2 [47], EDNRA (endothelin receptor type A) [48], EPHB4 [49], ALPK3 [50], WNT11 [51], IRAK2 [52], FBN1 [53], SFRP2 [54], CLCA2 [55], NEXN (nexilin F-actin binding protein) [56], PALLD (palladin, cytoskeletal associated protein) [57], DAB2 [58], NRP2 [59], THBS2 [60], CSF1R [61], KCNA2 [62], CACNA1C [63], F2R [64], UCHL1 [65], CCL18 [66], ITGB1BP2 [67] and FMOD ( bromodulin) [68] were reportedly involved in cardio vascular diseases, but these genes might be key for progression of obesity associated type 2 diabetes mellitus. Hu et al [69], Liu et al [70], Eltokhi et al [71], Cai et al [72], Pfeiffer et al [73], Lin et al [74], Royer-Zemmour et al [75], Pastor et al [76], Goodspeed et al [77], Zhang et al [78], Rogers et al [79], Su et al [80] and Foale et al [81] reported that NRXN1, CRHR1, SHANK2, PSEN2, CKB (creatine kinase B), CD200R1, SRPX2, PTPRZ1, SLC6A1, GABRB2, KCNA1, ASAH1 and LINGO1 were linked with progression of neuropsychiatric disorders, but these genes might be involved in advancement of obesity associated type 2 diabetes mellitus. Reports indicate that SPHK2 [82], NPC1L1 [83], CNTFR (ciliaryneurotrophic factor receptor)…”