Genome-wide association study for atopy and allergic rhinitis in a Singapore Chinese population
Allergic rhinitis (AR) is an atopic disease which affects about 600 million people worldwide and results from a complex interplay between genetic and environmental factors. However genetic association studies on known candidate genes yielded variable results. The aim of this study is to identify the...
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| creator | Andiappan, Anand Kumar Wang, De Yun Anantharaman, Ramani Parate, Pallavi Nilkanth Suri, Bani Kaur Low, Hui Qi Li, Yi Zhao, Wanting Castagnoli, Paola Liu, Jianjun Chew, Fook Tim |
| description | Allergic rhinitis (AR) is an atopic disease which affects about 600 million people worldwide and results from a complex interplay between genetic and environmental factors. However genetic association studies on known candidate genes yielded variable results. The aim of this study is to identify the genetic variants that influence predisposition towards allergic rhinitis in an ethnic Chinese population in Singapore using a genome-wide association study (GWAS) approach. A total of 4461 ethnic Chinese volunteers were recruited in Singapore and classified according to their allergic disease status. The GWAS included a discovery stage comparing 515 atopic cases (including 456 AR cases) and 486 non-allergic non-rhinitis (NANR) controls. The top SNPs were then validated in a replication cohort consisting of a separate 2323 atopic cases (including 676 AR cases) and 511 NANR controls. Two SNPs showed consistent association in both discovery and replication phases; MRPL4 SNP rs8111930 on 19q13.2 (OR = 0.69, P(combined) = 4.46×10(-05)) and BCAP SNP rs505010 on chromosome 10q24.1 (OR = 0.64, P(combined) = 1.10×10(-04)). In addition, we also replicated multiple associations within known candidates regions such as HLA-DQ and NPSR1 locus in the discovery phase. Our study suggests that MRPL4 and BCAP, key components of the HIF-1α and PI3K/Akt signaling pathways respectively, are two novel candidate genes for atopy and allergic rhinitis. Further study on these molecules and their signaling pathways would help in understanding of the pathogenesis of allergic rhinitis and identification of targets for new therapeutic intervention. |
| doi_str_mv | 10.1371/journal.pone.0019719 |
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However genetic association studies on known candidate genes yielded variable results. The aim of this study is to identify the genetic variants that influence predisposition towards allergic rhinitis in an ethnic Chinese population in Singapore using a genome-wide association study (GWAS) approach. A total of 4461 ethnic Chinese volunteers were recruited in Singapore and classified according to their allergic disease status. The GWAS included a discovery stage comparing 515 atopic cases (including 456 AR cases) and 486 non-allergic non-rhinitis (NANR) controls. The top SNPs were then validated in a replication cohort consisting of a separate 2323 atopic cases (including 676 AR cases) and 511 NANR controls. Two SNPs showed consistent association in both discovery and replication phases; MRPL4 SNP rs8111930 on 19q13.2 (OR = 0.69, P(combined) = 4.46×10(-05)) and BCAP SNP rs505010 on chromosome 10q24.1 (OR = 0.64, P(combined) = 1.10×10(-04)). In addition, we also replicated multiple associations within known candidates regions such as HLA-DQ and NPSR1 locus in the discovery phase. Our study suggests that MRPL4 and BCAP, key components of the HIF-1α and PI3K/Akt signaling pathways respectively, are two novel candidate genes for atopy and allergic rhinitis. Further study on these molecules and their signaling pathways would help in understanding of the pathogenesis of allergic rhinitis and identification of targets for new therapeutic intervention.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0019719</identifier><identifier>PMID: 21625490</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>1-Phosphatidylinositol 3-kinase ; AKT protein ; Allergic rhinitis ; Allergies ; Asian People - genetics ; Asthma ; Atopy ; B cells ; Biology ; Case-Control Studies ; Chromosome 10 ; Chronic obstructive pulmonary disease ; Critical care ; Disease ; Environmental factors ; Female ; Genes ; Genetic diversity ; Genetic Predisposition to Disease ; Genetic research ; Genetic variance ; Genetics ; Genome-wide association studies ; Genome-Wide Association Study ; Genomes ; Genomics ; Histocompatibility antigen HLA ; HLA antigens ; Humans ; Hypersensitivity - epidemiology ; Hypersensitivity - genetics ; Hypotheses ; Hypoxia ; Immunology ; Male ; Medicine ; Pathogenesis ; Pathways ; Permeability ; Phenotype ; Polymorphism, Single Nucleotide - genetics ; Population ; Principal components analysis ; Quality control ; Replication ; Rhinitis ; Rhinitis - epidemiology ; Rhinitis - genetics ; Signal transduction ; Signaling ; Singapore - epidemiology ; Single-nucleotide polymorphism ; Studies ; Target recognition ; Young Adult</subject><ispartof>PloS one, 2011-05, Vol.6 (5), p.e19719-e19719</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>2011 Andiappan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Andiappan et al. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c757t-139899bc7bdd3851bacb73a728a8c267cf3368b0462325b953881beb00f771643</citedby><cites>FETCH-LOGICAL-c757t-139899bc7bdd3851bacb73a728a8c267cf3368b0462325b953881beb00f771643</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098846/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098846/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21625490$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Andiappan, Anand Kumar</creatorcontrib><creatorcontrib>Wang, De Yun</creatorcontrib><creatorcontrib>Anantharaman, Ramani</creatorcontrib><creatorcontrib>Parate, Pallavi Nilkanth</creatorcontrib><creatorcontrib>Suri, Bani Kaur</creatorcontrib><creatorcontrib>Low, Hui Qi</creatorcontrib><creatorcontrib>Li, Yi</creatorcontrib><creatorcontrib>Zhao, Wanting</creatorcontrib><creatorcontrib>Castagnoli, Paola</creatorcontrib><creatorcontrib>Liu, Jianjun</creatorcontrib><creatorcontrib>Chew, Fook Tim</creatorcontrib><title>Genome-wide association study for atopy and allergic rhinitis in a Singapore Chinese population</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Allergic rhinitis (AR) is an atopic disease which affects about 600 million people worldwide and results from a complex interplay between genetic and environmental factors. However genetic association studies on known candidate genes yielded variable results. The aim of this study is to identify the genetic variants that influence predisposition towards allergic rhinitis in an ethnic Chinese population in Singapore using a genome-wide association study (GWAS) approach. A total of 4461 ethnic Chinese volunteers were recruited in Singapore and classified according to their allergic disease status. The GWAS included a discovery stage comparing 515 atopic cases (including 456 AR cases) and 486 non-allergic non-rhinitis (NANR) controls. The top SNPs were then validated in a replication cohort consisting of a separate 2323 atopic cases (including 676 AR cases) and 511 NANR controls. Two SNPs showed consistent association in both discovery and replication phases; MRPL4 SNP rs8111930 on 19q13.2 (OR = 0.69, P(combined) = 4.46×10(-05)) and BCAP SNP rs505010 on chromosome 10q24.1 (OR = 0.64, P(combined) = 1.10×10(-04)). In addition, we also replicated multiple associations within known candidates regions such as HLA-DQ and NPSR1 locus in the discovery phase. Our study suggests that MRPL4 and BCAP, key components of the HIF-1α and PI3K/Akt signaling pathways respectively, are two novel candidate genes for atopy and allergic rhinitis. Further study on these molecules and their signaling pathways would help in understanding of the pathogenesis of allergic rhinitis and identification of targets for new therapeutic intervention.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>AKT protein</subject><subject>Allergic rhinitis</subject><subject>Allergies</subject><subject>Asian People - genetics</subject><subject>Asthma</subject><subject>Atopy</subject><subject>B cells</subject><subject>Biology</subject><subject>Case-Control Studies</subject><subject>Chromosome 10</subject><subject>Chronic obstructive pulmonary disease</subject><subject>Critical care</subject><subject>Disease</subject><subject>Environmental factors</subject><subject>Female</subject><subject>Genes</subject><subject>Genetic diversity</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetic research</subject><subject>Genetic variance</subject><subject>Genetics</subject><subject>Genome-wide association studies</subject><subject>Genome-Wide Association Study</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Histocompatibility antigen HLA</subject><subject>HLA antigens</subject><subject>Humans</subject><subject>Hypersensitivity - epidemiology</subject><subject>Hypersensitivity - genetics</subject><subject>Hypotheses</subject><subject>Hypoxia</subject><subject>Immunology</subject><subject>Male</subject><subject>Medicine</subject><subject>Pathogenesis</subject><subject>Pathways</subject><subject>Permeability</subject><subject>Phenotype</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Population</subject><subject>Principal components analysis</subject><subject>Quality control</subject><subject>Replication</subject><subject>Rhinitis</subject><subject>Rhinitis - epidemiology</subject><subject>Rhinitis - genetics</subject><subject>Signal transduction</subject><subject>Signaling</subject><subject>Singapore - epidemiology</subject><subject>Single-nucleotide polymorphism</subject><subject>Studies</subject><subject>Target recognition</subject><subject>Young Adult</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk9-L1DAQx4so3nn6H4gWBMWHXZOmzY8X4Vj0XDg48NTXME3Tbo5sUpNW3f_e7G3v2Mo9SB4SJp_5TmYyk2UvMVpiwvCHGz8GB3bZe6eXCGHBsHiUnWJBigUtEHl8dD7JnsV4g1BFOKVPs5MC06IqBTrN5IV2fqsXv02jc4jRKwOD8S6Pw9js8taHHAbf73JwTQ7W6tAZlYeNcWYwMTcuh_zauA56H3S-SnYddd77frS3Os-zJy3YqF9M-1n2_fOnb6svi8uri_Xq_HKhWMWGBSaCC1ErVjcN4RWuQdWMACs4cFVQplpCKK9RSQtSVLVIiXBc6xqhljFMS3KWvT7o9tZHOdUmSlwIXrGyFEUi1gei8XAj-2C2EHbSg5G3Bh86CWEwymrZ0koAJaAKQUtWadEK0A2CBisGrSJJ6-MUbay3ulHaDQHsTHR-48xGdv6XJEhwXtIk8G4SCP7nqOMgtyYqbS047ccoORUVQ4SyRL75h3w4uYnqIL3fuNansGqvKc9LRrnAuNprLR-g0mr01qjUR61J9pnD-5lDYgb9Z-hgjFGur7_-P3v1Y86-PWI3Guywid6O-46Jc7A8gCr4GINu72uMkdyPwV015H4M5DQGye3V8f_cO931PfkLbnMC0g</recordid><startdate>20110520</startdate><enddate>20110520</enddate><creator>Andiappan, Anand Kumar</creator><creator>Wang, De Yun</creator><creator>Anantharaman, Ramani</creator><creator>Parate, Pallavi Nilkanth</creator><creator>Suri, Bani Kaur</creator><creator>Low, Hui Qi</creator><creator>Li, Yi</creator><creator>Zhao, Wanting</creator><creator>Castagnoli, Paola</creator><creator>Liu, Jianjun</creator><creator>Chew, Fook Tim</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20110520</creationdate><title>Genome-wide association study for atopy and allergic rhinitis in a Singapore Chinese population</title><author>Andiappan, Anand Kumar ; Wang, De Yun ; Anantharaman, Ramani ; Parate, Pallavi Nilkanth ; Suri, Bani Kaur ; Low, Hui Qi ; Li, Yi ; Zhao, Wanting ; Castagnoli, Paola ; Liu, Jianjun ; Chew, Fook Tim</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c757t-139899bc7bdd3851bacb73a728a8c267cf3368b0462325b953881beb00f771643</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>AKT protein</topic><topic>Allergic rhinitis</topic><topic>Allergies</topic><topic>Asian People - genetics</topic><topic>Asthma</topic><topic>Atopy</topic><topic>B cells</topic><topic>Biology</topic><topic>Case-Control Studies</topic><topic>Chromosome 10</topic><topic>Chronic obstructive pulmonary disease</topic><topic>Critical care</topic><topic>Disease</topic><topic>Environmental factors</topic><topic>Female</topic><topic>Genes</topic><topic>Genetic diversity</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetic research</topic><topic>Genetic variance</topic><topic>Genetics</topic><topic>Genome-wide association studies</topic><topic>Genome-Wide Association Study</topic><topic>Genomes</topic><topic>Genomics</topic><topic>Histocompatibility antigen HLA</topic><topic>HLA antigens</topic><topic>Humans</topic><topic>Hypersensitivity - epidemiology</topic><topic>Hypersensitivity - genetics</topic><topic>Hypotheses</topic><topic>Hypoxia</topic><topic>Immunology</topic><topic>Male</topic><topic>Medicine</topic><topic>Pathogenesis</topic><topic>Pathways</topic><topic>Permeability</topic><topic>Phenotype</topic><topic>Polymorphism, Single Nucleotide - 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However genetic association studies on known candidate genes yielded variable results. The aim of this study is to identify the genetic variants that influence predisposition towards allergic rhinitis in an ethnic Chinese population in Singapore using a genome-wide association study (GWAS) approach. A total of 4461 ethnic Chinese volunteers were recruited in Singapore and classified according to their allergic disease status. The GWAS included a discovery stage comparing 515 atopic cases (including 456 AR cases) and 486 non-allergic non-rhinitis (NANR) controls. The top SNPs were then validated in a replication cohort consisting of a separate 2323 atopic cases (including 676 AR cases) and 511 NANR controls. Two SNPs showed consistent association in both discovery and replication phases; MRPL4 SNP rs8111930 on 19q13.2 (OR = 0.69, P(combined) = 4.46×10(-05)) and BCAP SNP rs505010 on chromosome 10q24.1 (OR = 0.64, P(combined) = 1.10×10(-04)). In addition, we also replicated multiple associations within known candidates regions such as HLA-DQ and NPSR1 locus in the discovery phase. Our study suggests that MRPL4 and BCAP, key components of the HIF-1α and PI3K/Akt signaling pathways respectively, are two novel candidate genes for atopy and allergic rhinitis. Further study on these molecules and their signaling pathways would help in understanding of the pathogenesis of allergic rhinitis and identification of targets for new therapeutic intervention.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>21625490</pmid><doi>10.1371/journal.pone.0019719</doi><tpages>e19719</tpages><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1298574492 |
| source | PubMed Central (Open Access); MEDLINE; Full-Text Journals in Chemistry (Open access); DOAJ Directory of Open Access Journals; PLoS - Public Library of Sciencem (Open Access); EZB Electronic Journals Library |
| subjects | 1-Phosphatidylinositol 3-kinase AKT protein Allergic rhinitis Allergies Asian People - genetics Asthma Atopy B cells Biology Case-Control Studies Chromosome 10 Chronic obstructive pulmonary disease Critical care Disease Environmental factors Female Genes Genetic diversity Genetic Predisposition to Disease Genetic research Genetic variance Genetics Genome-wide association studies Genome-Wide Association Study Genomes Genomics Histocompatibility antigen HLA HLA antigens Humans Hypersensitivity - epidemiology Hypersensitivity - genetics Hypotheses Hypoxia Immunology Male Medicine Pathogenesis Pathways Permeability Phenotype Polymorphism, Single Nucleotide - genetics Population Principal components analysis Quality control Replication Rhinitis Rhinitis - epidemiology Rhinitis - genetics Signal transduction Signaling Singapore - epidemiology Single-nucleotide polymorphism Studies Target recognition Young Adult |
| title | Genome-wide association study for atopy and allergic rhinitis in a Singapore Chinese population |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-11T15%3A47%3A52IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Genome-wide%20association%20study%20for%20atopy%20and%20allergic%20rhinitis%20in%20a%20Singapore%20Chinese%20population&rft.jtitle=PloS%20one&rft.au=Andiappan,%20Anand%20Kumar&rft.date=2011-05-20&rft.volume=6&rft.issue=5&rft.spage=e19719&rft.epage=e19719&rft.pages=e19719-e19719&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0019719&rft_dat=%3Cgale_plos_%3EA476891157%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1298574492&rft_id=info:pmid/21625490&rft_galeid=A476891157&rft_doaj_id=oai_doaj_org_article_f659a63ac296475e9f9aed0ad1c7afc3&rfr_iscdi=true |