Genome‐scan for bipolar disorder with sib‐pair families in the Sardinian population: A new susceptibility locus on chromosome 1p22–p21?

Zompo, Maria Del; Severino, Giovanni; Ardau, Raffaella; Chillotti, Caterina; Piccardi, M.P.; Dib, Colette; Muzard, Gaëlle; Soubigou, Stéphane; Derock, Murielle; Fournel, Raphaël; Vaubien, Yves; Roche, Sandrine; Bowen-Squires, Laurent; Génin, Emmanuelle; Cousin, Emmanuelle; Deleuze, Jean‐François; Biguet, Nicole Faucon; Mallet, Jacques; Meloni, Rolando

doi:10.1002/ajmg.b.31092

Cited by 12 publications

(20 citation statements)

References 54 publications

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“…A genome-wide scan on a sample of 88 nuclear families with at least two affected sibs with bipolar disorder (BD) recruited in the Sardinian population, showed positive nonparametric linkage (NPL) scores exceeding 3.4 with P-values <0.0003 with two adjacent markers, D1S206 and D1S435 at 1p22-p21, a chromosomal region that had never been linked to BD before. Moreover, a subsequent fine mapping of the 1p22-p21 region confirmed the suggestive linkage finding for this region with NPL values above 2.2 and P-values < 0.02 for a cluster of nine markers comprising D1S435 (Del Zompo et al 2010).…”

Section: Introductionsupporting

confidence: 61%

“…2010). More specifically, it is less than 4000 kb on the telomeric side of D1S293, which with D1S424 and D1S2804 constitutes a block of markers displaying NPL scores exceeding 2.35.…”

Section: Resultsmentioning

confidence: 99%

“…Also, GPR88 is less than 700 kb on the centromeric side of D1S206, which is part of a series of markers displaying NPL score above 1.7, according to the results obtained using estimated allele frequencies in our previous linkage study (Del Zompo et al. 2010). …”

Section: Resultsmentioning

confidence: 99%

“…2010), we have assessed the genetic association of GPR88, a candidate gene located in this region, both with BD and SZ.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, a subsequent fine mapping of the 1p22-p21 region confirmed the suggestive linkage finding for this region with NPL values above 2.2 and P -values < 0.02 for a cluster of nine markers comprising D1S435 (Del Zompo et al. 2010). …”

Section: Introductionmentioning

confidence: 99%

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Association study in three different populations between the GPR88 gene and major psychoses

Zompo

Deleuze

Chillotti

et al. 2013

Molec Gen & Gen Med

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GPR88, coding for a G protein-coupled orphan receptor that is highly represented in the striatum, is a strong functional candidate gene for neuropsychiatric disorders and is located at 1p22-p21, a chromosomal region that we have previously linked to bipolar disorder (BD) in the Sardinian population. In order to ascertain the relevance of GPR88 as a risk factor for psychiatric diseases, we performed a genetic association analysis between GPR88 and BD in a sample of triads (patient and both parents) recruited in the Sardinian and the Palestinian population as well as between GPR88 and schizophrenia (SZ) in triads from the Xhosa population in South Africa. We found a positive association between GPR88 and BD in the Sardinian and Palestinian triads. Moreover, we found a positive association between GPR88 and SZ in triads from the Xhosa population in South Africa. When these results were corrected for multiple testing, the association between GPR88 and BD was maintained in the Palestinian population. Thus, these results suggest that GPR88 deserves consideration as a candidate gene for psychiatric diseases and requires to be further investigated in other populations.

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Section: Introductionsupporting

confidence: 61%

“…2010). More specifically, it is less than 4000 kb on the telomeric side of D1S293, which with D1S424 and D1S2804 constitutes a block of markers displaying NPL scores exceeding 2.35.…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…2010), we have assessed the genetic association of GPR88, a candidate gene located in this region, both with BD and SZ.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Association study in three different populations between the GPR88 gene and major psychoses

Zompo

Deleuze

Chillotti

et al. 2013

Molec Gen & Gen Med

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A genome‐wide linkage scan of bipolar disorder in Latino families identifies susceptibility loci at 8q24 and 14q32

Gonzalez

Camarillo

Rodriguez

et al. 2014

American J of Med Genetics Pt B

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A genome-wide nonparametric linkage screen was performed to localize Bipolar Disorder (BP) susceptibility loci in a sample of 3757 individuals of Latino ancestry. The sample included 963 individuals with BP phenotype (704 relative pairs) from 686 families recruited from the US, Mexico, Costa Rica, and Guatemala. Non-parametric analyses were performed over a 5 cM grid with an average genetic coverage of 0.67 cM. Multipoint analyses were conducted across the genome using non-parametric Kong & Cox LOD scores along with Sall statistics for all relative pairs. Suggestive and significant genome-wide thresholds were calculated based on 1000 simulations. Single-marker association tests in the presence of linkage were performed assuming a multiplicative model with a population prevalence of 2%. We identified two genome-wide significant susceptibly loci for BP at 8q24 and 14q32, and a third suggestive locus at 2q13-q14. Within these three linkage regions, the top associated single marker (rs1847694, P = 2.40 × 10(-5)) is located 195 Kb upstream of DPP10 in Chromosome 2. DPP10 is prominently expressed in brain neuronal populations, where it has been shown to bind and regulate Kv4-mediated A-type potassium channels. Taken together, these results provide additional evidence that 8q24, 14q32, and 2q13-q14 are susceptibly loci for BP and these regions may be involved in the pathogenesis of BP in the Latino population.

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Orphan Receptor GPR88 as an Emerging Neurotherapeutic Target

Mao

et al. 2018

ACS Chem. Neurosci.

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Although G protein-coupled receptors (GPCRs) are recognized as pivotal drug targets involved in multiple physiological and pathological processes, the majority of GPCRs including orphan GPCRs (oGPCRs) are unexploited. GPR88, a brain-specific oGPCR with particularly robust expression in the striatum, regulates diverse brain and behavioral functions, including cognition, mood, movement control, and reward-based learning, and is thus emerging as a novel drug target for central nervous system disorders including schizophrenia, Parkinson’s disease, anxiety, and addiction. Nevertheless, no effective GPR88 synthetic ligands have yet entered into clinical trials, and GPR88 endogenous ligands remain unknown. Despite the recent discovery and early stage study of several GPR88 agonists, such as 2-PCCA, RTI-13951–33, and phenylglycinol derivatives, further research into GPR88 pharmacology, medicinal chemistry, and chemical biology is urgently needed to yield structurally diversified GPR88-specific ligands. Drug-like pharmacological tool function and relevant signaling elucidation will also accelerate the evaluation of this receptor as a viable neurotherapeutic target.

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Genome‐scan for bipolar disorder with sib‐pair families in the Sardinian population: A new susceptibility locus on chromosome 1p22–p21?

Cited by 12 publications

References 54 publications

Association study in three different populations between the GPR88 gene and major psychoses

Association study in three different populations between the GPR88 gene and major psychoses

A genome‐wide linkage scan of bipolar disorder in Latino families identifies susceptibility loci at 8q24 and 14q32

Orphan Receptor GPR88 as an Emerging Neurotherapeutic Target

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