Screening ABCG1, the human homologue of the Drosophila white gene, for polymorphisms and association with bipolar affective disorder

Kirov, George; Lowry, Christopher A.; Stephens, M.F.C.; Oldfield, Susan; O'Donovan, Michael Conlon; Lightman, Stafford L.

doi:10.1038/sj.mp.4000899

Cited by 20 publications

(16 citation statements)

References 27 publications

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“…An allele of a poly T repeat polymorphism in the 3 0 UTR of the ABCG1 genes has shown association with mood and panic disorders. 26 However, no significant association of this polymorphism with bipolar disorder was detected by Kirov et al, 24 or by ourselves. In our analyses 'risk' haplotypes derived from markers showing high levels of marker to marker LD have been identified, but we have not yet been able to pinpoint any obvious pathogenic base pair changes.…”

Section: Discussionmentioning

confidence: 93%

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Fine mapping of a susceptibility locus for bipolar and genetically related unipolar affective disorders, to a region containing the C21ORF29 and TRPM2 genes on chromosome 21q22.3

et al. 2005

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Linkage analyses of bipolar families have confirmed that there is a susceptibility locus near the telomere on chromosome 21q. To fine map this locus we carried out tests of allelic association using 30 genetic markers near the telomere at 21q22.3 in 600 bipolar research subjects and 450 ancestrally matched supernormal control subjects. We found significant allelic association with the microsatellite markers D21S171 (P ¼ 0.016) and two closely linked single-nucleotide polymorphisms, rs1556314 (P ¼ 0.008) and rs1785467 (P ¼ 0.025). A test of association with a three locus haplotype across the susceptibility region was significant with a permutation test of P ¼ 0.011. A two SNP haplotype was also significantly associated with bipolar disorder (P ¼ 0.01). Only two brain expressed genes, TRPM2 and C21ORF29 (TSPEAR), are present in the associated region. TRPM2 encodes a calcium channel receptor and TSPEAR encodes a peptide with repeats associated with epilepsy in the mouse. DNA from subjects who had inherited the associated marker alleles was sequenced. A base pair change (rs1556314) in exon 11 of TRPM2, which caused a change from an aspartic acid to a glutamic acid at peptide position 543 was found. This SNP showed the strongest association with bipolar disorder (P ¼ 0.008). Deletion of exon 11 of TRPM2 is known to cause dysregulation of cellular calcium homeostasis in response to oxidative stress. A second nonconservative change from arginine to cysteine at position 755 in TRPM2 (ss48297761) was also detected. A third nonconservative change from histidine to glutamic acid was found in exon 8 of TSPEAR. These changes need further investigation to establish any aetiological role in bipolar disorder.

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Section: Discussionmentioning

confidence: 93%

“…24,25 Neither gene was associated with bipolar disorder, and no mutations were detected. An allele of a poly T repeat polymorphism in the 3 0 UTR of the ABCG1 genes has shown association with mood and panic disorders.…”

Section: Discussionmentioning

confidence: 99%

Fine mapping of a susceptibility locus for bipolar and genetically related unipolar affective disorders, to a region containing the C21ORF29 and TRPM2 genes on chromosome 21q22.3

et al. 2005

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“…13,71 Three were not association studies. 26,31,40 Four investigated other genes 37,43,64,65 and three investigated polymorphisms other than the 5-HTTLPR and the intron 2 VNTR. 36,45,55 Six papers studied a specific clinical feature of BPD rather than the illness itself.…”

Section: Resultsmentioning

confidence: 99%

Population-based and family-based studies on the serotonin transporter gene polymorphisms and bipolar disorder: a systematic review and meta-analysis

et al. 2005

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The serotonin transporter (5-HTT) is a candidate gene for bipolar disorder (BPD). It has been investigated for association with the illness in a series of studies, but overall results have been inconsistent and its role in the disorder remains controversial. Systematic reviews using metaanalytical techniques are a useful method for objectively and reproducibly assessing individual studies and generating combined results. We performed two meta-analyses of published studies-both population-based and family-based studies-investigating the association between BPD and the 5-HTT gene-linked polymorphic region (5-HTTLPR) and the intron 2 variable numbers of tandem repeats (VNTR) polymorphisms. The literature was searched using Medline and Embase to identify studies for inclusion. We statistically joined population-based and family-based studies into a single meta-analysis. For both polymorphisms, our review revealed significant pooled odds ratios (ORs): 1.12 (95% CI 1.03-1.21) for the 5-HTTLPR and 1.12 (95% CI 1.02-1.22) for the intron 2 VNTR. Meta-regression showed that neither the study type (population-based vs family-based; P ¼ 0.41 for the 5-HTTLPR and P ¼ 0.91 for the intron 2 VNTR) nor the sample ethnicity (Caucasian vs non-Caucasian; P ¼ 0.35 for the 5-HTTLPR and P ¼ 0.66 for the intron 2 VNTR) significantly contributed to the heterogeneity of the meta-analyses. The observed ORs could be regarded simply as a very small but detectable effect of the 5-HTT, which has an additive effect when combined with other susceptibility loci. Alternative hypotheses on this finding were also discussed: a stronger effect of the haplotypes involving the two polymorphisms or other SNP markers; a more direct effect of these polymorphisms on specific phenotypes of BPD; and the presence of gene-environment interaction as a mediator of the genetic effects of 5-HTT. Keywords: bipolar disorder; serotonin transporter; polymorphisms; genetics; association study; meta-analysis Bipolar disorder (BPD), also known as manic-depressive illness, is a frequent and severe psychiatric disorder with the lifetime prevalence between 1 and 2% in the general population, being equally distributed across sexes. 1 The etiology is unknown although the presence of a complex dysfunction at multiple levels such as neurotransmitter system, prefrontallimbic-subcortical circuit and neuroendocrinological system has been suggested. 2 Family studies have indicated a marked increase in lifetime risk of the illness in first-degree relatives of the proband, varying between five and 10 times that of the general population. 3 Twin studies have shown an increased risk in monozygotic co-twins compared with dizygotic co-twins of a proband with BPD. The risk in monozygotic co-twins has been estimated at 45-75 times that of the general population. 3,4 Adoption studies have also shown that the risk of BPD is greater in biological relatives than in adoptive relatives of the probands. 5 Most of the segregation studies have shown that the inheritance of BPD cannot be explained b...

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“…All three variants were scored blindly by two individuals. The À32A > G SNP in Ga t2 was analysed using the primer extension technique as described by Kirov et al [2001] using a 373 DNA sequencer, and the data were analysed using the ABI GENESCAN analysis and GENOTYPER software.…”

Section: Individual Genotypingmentioning

confidence: 99%

Direct analysis of the genes encoding G proteins Gα_T2, Gα_o, Gα_Z in ADHD

Turic

Langley

Kirov

et al. 2004

American J of Med Genetics Pt B

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We have followed up the extensive replicated evidence that the dopamine DRD4 receptor is involved in the aetiology of ADHD by undertaking direct analysis of genes encoding other proteins in this effector system. We prioritised the genes encoding G protein alpha subunits G alpha(T2), G alpha(o), G alpha(Z) as these have been shown to transduce the effects of ligand binding at DRD4. We screened the exons of all three genes for sequence variation in 28 unrelated subjects with ADHD and identified 13 novel polymorphisms. All were tested for possible association with ADHD using a combination of pooled and individual genotyping. The results of our study do not suggest that polymorphisms in these genes contribute to susceptibility to ADHD.

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Screening ABCG1, the human homologue of the Drosophila white gene, for polymorphisms and association with bipolar affective disorder

Cited by 20 publications

References 27 publications

Fine mapping of a susceptibility locus for bipolar and genetically related unipolar affective disorders, to a region containing the C21ORF29 and TRPM2 genes on chromosome 21q22.3

Fine mapping of a susceptibility locus for bipolar and genetically related unipolar affective disorders, to a region containing the C21ORF29 and TRPM2 genes on chromosome 21q22.3

Population-based and family-based studies on the serotonin transporter gene polymorphisms and bipolar disorder: a systematic review and meta-analysis

Direct analysis of the genes encoding G proteins Gα_T2, Gα_o, Gα_Z in ADHD

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Screening ABCG1, the human homologue of the Drosophila white gene, for polymorphisms and association with bipolar affective disorder

Cited by 20 publications

References 27 publications

Fine mapping of a susceptibility locus for bipolar and genetically related unipolar affective disorders, to a region containing the C21ORF29 and TRPM2 genes on chromosome 21q22.3

Fine mapping of a susceptibility locus for bipolar and genetically related unipolar affective disorders, to a region containing the C21ORF29 and TRPM2 genes on chromosome 21q22.3

Population-based and family-based studies on the serotonin transporter gene polymorphisms and bipolar disorder: a systematic review and meta-analysis

Direct analysis of the genes encoding G proteins GαT2, Gαo, GαZ in ADHD

Contact Info

Product

Resources

About

Direct analysis of the genes encoding G proteins Gα_T2, Gα_o, Gα_Z in ADHD