Association analyses suggest GPR24 as a shared susceptibility gene for bipolar affective disorder and schizophrenia

J E Severinsen, T D Als, H Binderup, T A Kruse, A G Wang, M Vang, W J Muir, D H R Blackwood, O Mors, A D Børglum

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Linkage analyses suggest that chromosome 22q12-13 may harbor a shared susceptibility locus for bipolar affective disorder (BPD) and schizophrenia (SZ). In a study of a sample from the Faeroe Islands we have previously reported association between both disorders and microsatellite markers in a 3.6 cM segment on 22q13. The present study investigated three candidate genes located in this segment: GPR24, ADSL, and ST13. Nine SNPs located in these genes and one microsatellite marker (D22S279) were applied in an association analysis of two samples: an extension of the previously analyzed Faeroese sample comprising 28 distantly related cases (17 BPD, 11 SZ subjects) and 44 controls, and a Scottish sample including 162 patients with BPD, 103 with SZ, and 200 controls. In both samples significant associations were observed in both disorders with predominantly GPR24 SNPs and haplotypes. In the Faeroese sample overall P-values of 0.0009, 0.0054, and 0.0023 were found for haplotypes in BPD, SZ, and combined cases, respectively, and in the Scottish sample overall P-values of 0.0003, 0.0005, and 0.016 were observed for similar groupings. Specific haplotypes showed associations with lowest P-values of 7 x 10(-5) and 0.0006 in the combined group of cases from the Faeroe Islands and Scotland, respectively. The G protein-coupled receptor 24 encoded by GPR24 binds melanin-concentrating hormone (MCH) and has been implicated with feeding behavior, energy metabolism, and regulation of stress and mood. To our knowledge this is the first study reporting association between GPR24 and BPD and SZ, suggesting that GPR24 variants may confer susceptibility to both disorders.

OriginalsprogEngelsk
TidsskriftAmerican Journal of Medical Genetics. Part B: Neuropsychiatric Genetics
Vol/bind141B
Udgave nummer5
Sider (fra-til)524-33
ISSN1552-4841
DOI
StatusUdgivet - 5. jul. 2006

Fingeraftryk

Haplotypes
Denmark
Single Nucleotide Polymorphism
Chromosomes, Human, Pair 13
Scotland
G-Protein-Coupled Receptors
Energy Metabolism

Citer dette

Severinsen, J E ; Als, T D ; Binderup, H ; Kruse, T A ; Wang, A G ; Vang, M ; Muir, W J ; Blackwood, D H R ; Mors, O ; Børglum, A D. / Association analyses suggest GPR24 as a shared susceptibility gene for bipolar affective disorder and schizophrenia. I: American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics. 2006 ; Bind 141B, Nr. 5. s. 524-33.
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title = "Association analyses suggest GPR24 as a shared susceptibility gene for bipolar affective disorder and schizophrenia",
abstract = "Linkage analyses suggest that chromosome 22q12-13 may harbor a shared susceptibility locus for bipolar affective disorder (BPD) and schizophrenia (SZ). In a study of a sample from the Faeroe Islands we have previously reported association between both disorders and microsatellite markers in a 3.6 cM segment on 22q13. The present study investigated three candidate genes located in this segment: GPR24, ADSL, and ST13. Nine SNPs located in these genes and one microsatellite marker (D22S279) were applied in an association analysis of two samples: an extension of the previously analyzed Faeroese sample comprising 28 distantly related cases (17 BPD, 11 SZ subjects) and 44 controls, and a Scottish sample including 162 patients with BPD, 103 with SZ, and 200 controls. In both samples significant associations were observed in both disorders with predominantly GPR24 SNPs and haplotypes. In the Faeroese sample overall P-values of 0.0009, 0.0054, and 0.0023 were found for haplotypes in BPD, SZ, and combined cases, respectively, and in the Scottish sample overall P-values of 0.0003, 0.0005, and 0.016 were observed for similar groupings. Specific haplotypes showed associations with lowest P-values of 7 x 10(-5) and 0.0006 in the combined group of cases from the Faeroe Islands and Scotland, respectively. The G protein-coupled receptor 24 encoded by GPR24 binds melanin-concentrating hormone (MCH) and has been implicated with feeding behavior, energy metabolism, and regulation of stress and mood. To our knowledge this is the first study reporting association between GPR24 and BPD and SZ, suggesting that GPR24 variants may confer susceptibility to both disorders.",
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Association analyses suggest GPR24 as a shared susceptibility gene for bipolar affective disorder and schizophrenia. / Severinsen, J E; Als, T D; Binderup, H; Kruse, T A; Wang, A G; Vang, M; Muir, W J; Blackwood, D H R; Mors, O; Børglum, A D.

I: American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics, Bind 141B, Nr. 5, 05.07.2006, s. 524-33.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Association analyses suggest GPR24 as a shared susceptibility gene for bipolar affective disorder and schizophrenia

AU - Severinsen, J E

AU - Als, T D

AU - Binderup, H

AU - Kruse, T A

AU - Wang, A G

AU - Vang, M

AU - Muir, W J

AU - Blackwood, D H R

AU - Mors, O

AU - Børglum, A D

N1 - (c) 2006 Wiley-Liss, Inc.

PY - 2006/7/5

Y1 - 2006/7/5

N2 - Linkage analyses suggest that chromosome 22q12-13 may harbor a shared susceptibility locus for bipolar affective disorder (BPD) and schizophrenia (SZ). In a study of a sample from the Faeroe Islands we have previously reported association between both disorders and microsatellite markers in a 3.6 cM segment on 22q13. The present study investigated three candidate genes located in this segment: GPR24, ADSL, and ST13. Nine SNPs located in these genes and one microsatellite marker (D22S279) were applied in an association analysis of two samples: an extension of the previously analyzed Faeroese sample comprising 28 distantly related cases (17 BPD, 11 SZ subjects) and 44 controls, and a Scottish sample including 162 patients with BPD, 103 with SZ, and 200 controls. In both samples significant associations were observed in both disorders with predominantly GPR24 SNPs and haplotypes. In the Faeroese sample overall P-values of 0.0009, 0.0054, and 0.0023 were found for haplotypes in BPD, SZ, and combined cases, respectively, and in the Scottish sample overall P-values of 0.0003, 0.0005, and 0.016 were observed for similar groupings. Specific haplotypes showed associations with lowest P-values of 7 x 10(-5) and 0.0006 in the combined group of cases from the Faeroe Islands and Scotland, respectively. The G protein-coupled receptor 24 encoded by GPR24 binds melanin-concentrating hormone (MCH) and has been implicated with feeding behavior, energy metabolism, and regulation of stress and mood. To our knowledge this is the first study reporting association between GPR24 and BPD and SZ, suggesting that GPR24 variants may confer susceptibility to both disorders.

AB - Linkage analyses suggest that chromosome 22q12-13 may harbor a shared susceptibility locus for bipolar affective disorder (BPD) and schizophrenia (SZ). In a study of a sample from the Faeroe Islands we have previously reported association between both disorders and microsatellite markers in a 3.6 cM segment on 22q13. The present study investigated three candidate genes located in this segment: GPR24, ADSL, and ST13. Nine SNPs located in these genes and one microsatellite marker (D22S279) were applied in an association analysis of two samples: an extension of the previously analyzed Faeroese sample comprising 28 distantly related cases (17 BPD, 11 SZ subjects) and 44 controls, and a Scottish sample including 162 patients with BPD, 103 with SZ, and 200 controls. In both samples significant associations were observed in both disorders with predominantly GPR24 SNPs and haplotypes. In the Faeroese sample overall P-values of 0.0009, 0.0054, and 0.0023 were found for haplotypes in BPD, SZ, and combined cases, respectively, and in the Scottish sample overall P-values of 0.0003, 0.0005, and 0.016 were observed for similar groupings. Specific haplotypes showed associations with lowest P-values of 7 x 10(-5) and 0.0006 in the combined group of cases from the Faeroe Islands and Scotland, respectively. The G protein-coupled receptor 24 encoded by GPR24 binds melanin-concentrating hormone (MCH) and has been implicated with feeding behavior, energy metabolism, and regulation of stress and mood. To our knowledge this is the first study reporting association between GPR24 and BPD and SZ, suggesting that GPR24 variants may confer susceptibility to both disorders.

KW - Bipolar Disorder

KW - Case-Control Studies

KW - Denmark

KW - Female

KW - Gene Frequency

KW - Genetic Predisposition to Disease

KW - Genotype

KW - Haplotypes

KW - Humans

KW - Linkage Disequilibrium

KW - Male

KW - Pedigree

KW - Polymorphism, Single Nucleotide

KW - Receptors, Somatostatin

KW - Schizophrenia

KW - Scotland

KW - Comparative Study

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1002/ajmg.b.30335

DO - 10.1002/ajmg.b.30335

M3 - Journal article

C2 - 16741940

VL - 141B

SP - 524

EP - 533

JO - American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics

JF - American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics

SN - 1552-4841

IS - 5

ER -