Association analysis of the chromosome 4p-located G protein-coupled receptor 78 (GPR78) gene in bipolar affective disorder and schizophrenia
The orphan G protein-coupled receptor 78 ( GPR78 ) gene lies within a region of chromosome 4p where we have previously shown linkage to bipolar affective disorder (BPAD) in a large Scottish family. GPR78 was screened for single-nucleotide polymorphisms (SNPs) and a linkage disequilibrium map was con...
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| Veröffentlicht in: | Molecular psychiatry 2006-04, Vol.11 (4), p.384-394 |
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| creator | Underwood, S L Christoforou, A Thomson, P A Wray, N R Tenesa, A Whittaker, J Adams, R A Le Hellard, S Morris, S W Blackwood, D H R Muir, W J Porteous, D J Evans, K L |
| description | The orphan
G protein-coupled receptor 78
(
GPR78
) gene lies within a region of chromosome 4p where we have previously shown linkage to bipolar affective disorder (BPAD) in a large Scottish family.
GPR78
was screened for single-nucleotide polymorphisms (SNPs) and a linkage disequilibrium map was constructed. Six tagging SNPs were selected and tested for association on a sample of 377 BPAD, 392 schizophrenia (SCZ) and 470 control individuals. Using standard
χ
2
statistics and a backwards logistic regression approach to adjust for the effect of sex, SNP rs1282, located approximately 3 kb upstream of the coding region, was identified as a potentially important variant in SCZ (
χ
2
P
=0.044; LRT
P
=0.065). When the analysis was restricted to females, the strength of association increased to an uncorrected allele
P
-value of 0.015 (odds ratios (OR)=1.688, 95% confidence intervals (CI): 1.104–2.581) and uncorrected genotype
P
-value of 0.015 (OR=5.991, 95% CI: 1.545–23.232). Under the recessive model, the genotype
P
-value improved further to 0.005 (OR=5.618, 95% CI: 1.460–21.617) and remained significant after correcting for multiple testing (
P
=0.017). No single-marker association was detected in the SCZ males, in the BPAD individuals or with any other SNP. Haplotype analysis of the case–control samples revealed several global and individual haplotypes, with
P
-values |
| doi_str_mv | 10.1038/sj.mp.4001786 |
| format | Article |
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G protein-coupled receptor 78
(
GPR78
) gene lies within a region of chromosome 4p where we have previously shown linkage to bipolar affective disorder (BPAD) in a large Scottish family.
GPR78
was screened for single-nucleotide polymorphisms (SNPs) and a linkage disequilibrium map was constructed. Six tagging SNPs were selected and tested for association on a sample of 377 BPAD, 392 schizophrenia (SCZ) and 470 control individuals. Using standard
χ
2
statistics and a backwards logistic regression approach to adjust for the effect of sex, SNP rs1282, located approximately 3 kb upstream of the coding region, was identified as a potentially important variant in SCZ (
χ
2
P
=0.044; LRT
P
=0.065). When the analysis was restricted to females, the strength of association increased to an uncorrected allele
P
-value of 0.015 (odds ratios (OR)=1.688, 95% confidence intervals (CI): 1.104–2.581) and uncorrected genotype
P
-value of 0.015 (OR=5.991, 95% CI: 1.545–23.232). Under the recessive model, the genotype
P
-value improved further to 0.005 (OR=5.618, 95% CI: 1.460–21.617) and remained significant after correcting for multiple testing (
P
=0.017). No single-marker association was detected in the SCZ males, in the BPAD individuals or with any other SNP. Haplotype analysis of the case–control samples revealed several global and individual haplotypes, with
P
-values <0.05, all but one of which contained SNP rs1282. After correcting for multiple testing, two haplotypes remained significant in both the female BPAD individuals (
P
=0.038 and 0.032) and in the full sample of affected female individuals (
P
=0.044 and 0.033). Our results provide preliminary evidence for the involvement of
GPR78
in susceptibility to BPAD and SCZ in the Scottish population.</description><identifier>ISSN: 1359-4184</identifier><identifier>EISSN: 1476-5578</identifier><identifier>DOI: 10.1038/sj.mp.4001786</identifier><identifier>PMID: 16389273</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Association analysis ; Behavioral Sciences ; Biological Psychology ; Bipolar disorder ; Bipolar Disorder - genetics ; Case-Control Studies ; Chi-Square Distribution ; Chromosome 4 ; Chromosome Mapping ; Chromosomes ; Chromosomes, Human, Pair 4 - genetics ; Endoplasmic Reticulum Chaperone BiP ; Female ; Females ; Genetic Predisposition to Disease ; Genetics ; Genomes ; Haplotypes ; Humans ; Ligands ; Linkage disequilibrium ; Lod Score ; Logistic Models ; Male ; Medicine ; Medicine & Public Health ; Mental disorders ; Neurosciences ; original-article ; Pedigree ; Pharmacotherapy ; Polymorphism, Single Nucleotide - genetics ; Proteins ; Psychiatry ; Receptors, G-Protein-Coupled - genetics ; Receptors, Neuropeptide - genetics ; Schizophrenia ; Schizophrenia - genetics ; Sex Factors ; Single-nucleotide polymorphism ; Statistical analysis</subject><ispartof>Molecular psychiatry, 2006-04, Vol.11 (4), p.384-394</ispartof><rights>Springer Nature Limited 2006</rights><rights>Molecular Psychiatry (2006) 11, 384-394. doi:10.1038/sj.mp.4001786; published online 3 January 2006.</rights><rights>COPYRIGHT 2006 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Apr 2006</rights><rights>Nature Publishing Group 2006.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c589t-dd8a82d66b230ea7eae24fbd378bc276b876de843aef39e6740d340adceb86483</citedby><cites>FETCH-LOGICAL-c589t-dd8a82d66b230ea7eae24fbd378bc276b876de843aef39e6740d340adceb86483</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/sj.mp.4001786$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/sj.mp.4001786$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16389273$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Underwood, S L</creatorcontrib><creatorcontrib>Christoforou, A</creatorcontrib><creatorcontrib>Thomson, P A</creatorcontrib><creatorcontrib>Wray, N R</creatorcontrib><creatorcontrib>Tenesa, A</creatorcontrib><creatorcontrib>Whittaker, J</creatorcontrib><creatorcontrib>Adams, R A</creatorcontrib><creatorcontrib>Le Hellard, S</creatorcontrib><creatorcontrib>Morris, S W</creatorcontrib><creatorcontrib>Blackwood, D H R</creatorcontrib><creatorcontrib>Muir, W J</creatorcontrib><creatorcontrib>Porteous, D J</creatorcontrib><creatorcontrib>Evans, K L</creatorcontrib><title>Association analysis of the chromosome 4p-located G protein-coupled receptor 78 (GPR78) gene in bipolar affective disorder and schizophrenia</title><title>Molecular psychiatry</title><addtitle>Mol Psychiatry</addtitle><addtitle>Mol Psychiatry</addtitle><description>The orphan
G protein-coupled receptor 78
(
GPR78
) gene lies within a region of chromosome 4p where we have previously shown linkage to bipolar affective disorder (BPAD) in a large Scottish family.
GPR78
was screened for single-nucleotide polymorphisms (SNPs) and a linkage disequilibrium map was constructed. Six tagging SNPs were selected and tested for association on a sample of 377 BPAD, 392 schizophrenia (SCZ) and 470 control individuals. Using standard
χ
2
statistics and a backwards logistic regression approach to adjust for the effect of sex, SNP rs1282, located approximately 3 kb upstream of the coding region, was identified as a potentially important variant in SCZ (
χ
2
P
=0.044; LRT
P
=0.065). When the analysis was restricted to females, the strength of association increased to an uncorrected allele
P
-value of 0.015 (odds ratios (OR)=1.688, 95% confidence intervals (CI): 1.104–2.581) and uncorrected genotype
P
-value of 0.015 (OR=5.991, 95% CI: 1.545–23.232). Under the recessive model, the genotype
P
-value improved further to 0.005 (OR=5.618, 95% CI: 1.460–21.617) and remained significant after correcting for multiple testing (
P
=0.017). No single-marker association was detected in the SCZ males, in the BPAD individuals or with any other SNP. Haplotype analysis of the case–control samples revealed several global and individual haplotypes, with
P
-values <0.05, all but one of which contained SNP rs1282. After correcting for multiple testing, two haplotypes remained significant in both the female BPAD individuals (
P
=0.038 and 0.032) and in the full sample of affected female individuals (
P
=0.044 and 0.033). Our results provide preliminary evidence for the involvement of
GPR78
in susceptibility to BPAD and SCZ in the Scottish population.</description><subject>Association analysis</subject><subject>Behavioral Sciences</subject><subject>Biological Psychology</subject><subject>Bipolar disorder</subject><subject>Bipolar Disorder - genetics</subject><subject>Case-Control Studies</subject><subject>Chi-Square Distribution</subject><subject>Chromosome 4</subject><subject>Chromosome Mapping</subject><subject>Chromosomes</subject><subject>Chromosomes, Human, Pair 4 - genetics</subject><subject>Endoplasmic Reticulum Chaperone BiP</subject><subject>Female</subject><subject>Females</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetics</subject><subject>Genomes</subject><subject>Haplotypes</subject><subject>Humans</subject><subject>Ligands</subject><subject>Linkage disequilibrium</subject><subject>Lod Score</subject><subject>Logistic Models</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mental disorders</subject><subject>Neurosciences</subject><subject>original-article</subject><subject>Pedigree</subject><subject>Pharmacotherapy</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Proteins</subject><subject>Psychiatry</subject><subject>Receptors, G-Protein-Coupled - genetics</subject><subject>Receptors, Neuropeptide - genetics</subject><subject>Schizophrenia</subject><subject>Schizophrenia - genetics</subject><subject>Sex Factors</subject><subject>Single-nucleotide polymorphism</subject><subject>Statistical analysis</subject><issn>1359-4184</issn><issn>1476-5578</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kkuLFDEQxxtR3IcevUpQ8HHoMemkk_RxWNZRWFBEzyGdVM9k6E7aJC2sn8EPbYYdGJRVckio-tW_HqmqekbwimAq36X9appXDGMiJH9QnRMmeN22Qj4sb9p2NSOSnVUXKe0LU5zt4-qMcCq7RtDz6tc6pWCczi54pL0eb5NLKAwo7wCZXQxTSGECxOZ6DEZnsGiD5hgyOF-bsMxjsUQwMOcQkZDozebzFyHfoi14QM6j3s1h1BHpYQCT3Q9A1qUQLRSTtyiZnfsZ5l0E7_ST6tGgxwRPj_dl9e399derD_XNp83Hq_VNbVrZ5dpaqWVjOe8bikEL0NCwobdUyN40gvdScAuSUQ0D7YALhi1lWFsDveRM0svq9Z1uaeT7AimrySUD46g9hCUp0Xa0jEgcyFf_JbmQWBa0gC__AvdhiWWeSTWctaItX0IK9eKfVEOIaAjHJ6mtHkE5P4QctTnkVWsiZct4h0WhVvdQ5ViYnAkeBlfsfwTUdwEmhpQiDGqObtLxVhGsDquk0l5NszquUuGfH2td-gnsiT7uzqmCVFx-C_HUzP2KvwGqWNL5</recordid><startdate>20060401</startdate><enddate>20060401</enddate><creator>Underwood, S L</creator><creator>Christoforou, A</creator><creator>Thomson, P A</creator><creator>Wray, N R</creator><creator>Tenesa, A</creator><creator>Whittaker, J</creator><creator>Adams, R A</creator><creator>Le Hellard, S</creator><creator>Morris, S W</creator><creator>Blackwood, D H R</creator><creator>Muir, W J</creator><creator>Porteous, D J</creator><creator>Evans, K L</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20060401</creationdate><title>Association analysis of the chromosome 4p-located G protein-coupled receptor 78 (GPR78) gene in bipolar affective disorder and schizophrenia</title><author>Underwood, S L ; Christoforou, A ; Thomson, P A ; Wray, N R ; Tenesa, A ; Whittaker, J ; Adams, R A ; Le Hellard, S ; Morris, S W ; Blackwood, D H R ; Muir, W J ; Porteous, D J ; Evans, K L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c589t-dd8a82d66b230ea7eae24fbd378bc276b876de843aef39e6740d340adceb86483</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Association analysis</topic><topic>Behavioral Sciences</topic><topic>Biological Psychology</topic><topic>Bipolar disorder</topic><topic>Bipolar Disorder - genetics</topic><topic>Case-Control Studies</topic><topic>Chi-Square Distribution</topic><topic>Chromosome 4</topic><topic>Chromosome Mapping</topic><topic>Chromosomes</topic><topic>Chromosomes, Human, Pair 4 - genetics</topic><topic>Endoplasmic Reticulum Chaperone BiP</topic><topic>Female</topic><topic>Females</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetics</topic><topic>Genomes</topic><topic>Haplotypes</topic><topic>Humans</topic><topic>Ligands</topic><topic>Linkage disequilibrium</topic><topic>Lod Score</topic><topic>Logistic Models</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mental disorders</topic><topic>Neurosciences</topic><topic>original-article</topic><topic>Pedigree</topic><topic>Pharmacotherapy</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>Proteins</topic><topic>Psychiatry</topic><topic>Receptors, G-Protein-Coupled - genetics</topic><topic>Receptors, Neuropeptide - genetics</topic><topic>Schizophrenia</topic><topic>Schizophrenia - genetics</topic><topic>Sex Factors</topic><topic>Single-nucleotide polymorphism</topic><topic>Statistical analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Underwood, S L</creatorcontrib><creatorcontrib>Christoforou, A</creatorcontrib><creatorcontrib>Thomson, P A</creatorcontrib><creatorcontrib>Wray, N R</creatorcontrib><creatorcontrib>Tenesa, A</creatorcontrib><creatorcontrib>Whittaker, J</creatorcontrib><creatorcontrib>Adams, R A</creatorcontrib><creatorcontrib>Le Hellard, S</creatorcontrib><creatorcontrib>Morris, S W</creatorcontrib><creatorcontrib>Blackwood, D H R</creatorcontrib><creatorcontrib>Muir, W J</creatorcontrib><creatorcontrib>Porteous, D J</creatorcontrib><creatorcontrib>Evans, K L</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Psychology</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular psychiatry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Underwood, S L</au><au>Christoforou, A</au><au>Thomson, P A</au><au>Wray, N R</au><au>Tenesa, A</au><au>Whittaker, J</au><au>Adams, R A</au><au>Le Hellard, S</au><au>Morris, S W</au><au>Blackwood, D H R</au><au>Muir, W J</au><au>Porteous, D J</au><au>Evans, K L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association analysis of the chromosome 4p-located G protein-coupled receptor 78 (GPR78) gene in bipolar affective disorder and schizophrenia</atitle><jtitle>Molecular psychiatry</jtitle><stitle>Mol Psychiatry</stitle><addtitle>Mol Psychiatry</addtitle><date>2006-04-01</date><risdate>2006</risdate><volume>11</volume><issue>4</issue><spage>384</spage><epage>394</epage><pages>384-394</pages><issn>1359-4184</issn><eissn>1476-5578</eissn><abstract>The orphan
G protein-coupled receptor 78
(
GPR78
) gene lies within a region of chromosome 4p where we have previously shown linkage to bipolar affective disorder (BPAD) in a large Scottish family.
GPR78
was screened for single-nucleotide polymorphisms (SNPs) and a linkage disequilibrium map was constructed. Six tagging SNPs were selected and tested for association on a sample of 377 BPAD, 392 schizophrenia (SCZ) and 470 control individuals. Using standard
χ
2
statistics and a backwards logistic regression approach to adjust for the effect of sex, SNP rs1282, located approximately 3 kb upstream of the coding region, was identified as a potentially important variant in SCZ (
χ
2
P
=0.044; LRT
P
=0.065). When the analysis was restricted to females, the strength of association increased to an uncorrected allele
P
-value of 0.015 (odds ratios (OR)=1.688, 95% confidence intervals (CI): 1.104–2.581) and uncorrected genotype
P
-value of 0.015 (OR=5.991, 95% CI: 1.545–23.232). Under the recessive model, the genotype
P
-value improved further to 0.005 (OR=5.618, 95% CI: 1.460–21.617) and remained significant after correcting for multiple testing (
P
=0.017). No single-marker association was detected in the SCZ males, in the BPAD individuals or with any other SNP. Haplotype analysis of the case–control samples revealed several global and individual haplotypes, with
P
-values <0.05, all but one of which contained SNP rs1282. After correcting for multiple testing, two haplotypes remained significant in both the female BPAD individuals (
P
=0.038 and 0.032) and in the full sample of affected female individuals (
P
=0.044 and 0.033). Our results provide preliminary evidence for the involvement of
GPR78
in susceptibility to BPAD and SCZ in the Scottish population.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>16389273</pmid><doi>10.1038/sj.mp.4001786</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1359-4184 |
| ispartof | Molecular psychiatry, 2006-04, Vol.11 (4), p.384-394 |
| issn | 1359-4184 1476-5578 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_759316378 |
| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Association analysis Behavioral Sciences Biological Psychology Bipolar disorder Bipolar Disorder - genetics Case-Control Studies Chi-Square Distribution Chromosome 4 Chromosome Mapping Chromosomes Chromosomes, Human, Pair 4 - genetics Endoplasmic Reticulum Chaperone BiP Female Females Genetic Predisposition to Disease Genetics Genomes Haplotypes Humans Ligands Linkage disequilibrium Lod Score Logistic Models Male Medicine Medicine & Public Health Mental disorders Neurosciences original-article Pedigree Pharmacotherapy Polymorphism, Single Nucleotide - genetics Proteins Psychiatry Receptors, G-Protein-Coupled - genetics Receptors, Neuropeptide - genetics Schizophrenia Schizophrenia - genetics Sex Factors Single-nucleotide polymorphism Statistical analysis |
| title | Association analysis of the chromosome 4p-located G protein-coupled receptor 78 (GPR78) gene in bipolar affective disorder and schizophrenia |
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