A genome-wide association study of hepatitis B vaccine response in an Indonesian population reveals multiple independent risk variants in the HLA region
We performed a two-stage genome-wide association study (GWAS) of antibody titer in 3614 hepatitis B vaccine recipients from Indonesia's Riau Archipelago, leading to the identification of at least three independent signals within the human leukocyte antigen (HLA) complex. These appear to implica...
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| Veröffentlicht in: | Human molecular genetics 2011-10, Vol.20 (19), p.3893-3898 |
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| container_title | Human molecular genetics |
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| creator | Png, Eileen Thalamuthu, Anbupalam Ong, Rick T.H. Snippe, Harm Boland, Greet J. Seielstad, Mark |
| description | We performed a two-stage genome-wide association study (GWAS) of antibody titer in 3614 hepatitis B vaccine recipients from Indonesia's Riau Archipelago, leading to the identification of at least three independent signals within the human leukocyte antigen (HLA) complex. These appear to implicate HLA-DR [rs3135363; P= 6.53 × 10−22; odds ratio (OR) = 1.53, 95% confidence interval (CI) = 1.35-1.74]; HLA-DP, previously associated with the risk of chronic hepatitis B infection (rs9277535; P= 2.91 × 10−12; OR = 0.72, 95% CI = 0.63-0.81); and a gene rich HLA Class III interval (rs9267665; P = 1.24 × 10−17; OR = 2.05, CI = 1.64-2.57). The substantial overlap of these variants and those identified by GWAS of chronic hepatitis B infection confirms vaccine response as a model for infection, while suggesting that the vaccine is least effective in those most at risk of lifelong infection, following exposure to the virus. |
| doi_str_mv | 10.1093/hmg/ddr302 |
| format | Article |
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These appear to implicate HLA-DR [rs3135363; P= 6.53 × 10−22; odds ratio (OR) = 1.53, 95% confidence interval (CI) = 1.35-1.74]; HLA-DP, previously associated with the risk of chronic hepatitis B infection (rs9277535; P= 2.91 × 10−12; OR = 0.72, 95% CI = 0.63-0.81); and a gene rich HLA Class III interval (rs9267665; P = 1.24 × 10−17; OR = 2.05, CI = 1.64-2.57). The substantial overlap of these variants and those identified by GWAS of chronic hepatitis B infection confirms vaccine response as a model for infection, while suggesting that the vaccine is least effective in those most at risk of lifelong infection, following exposure to the virus.</description><identifier>ISSN: 0964-6906</identifier><identifier>EISSN: 1460-2083</identifier><identifier>DOI: 10.1093/hmg/ddr302</identifier><identifier>PMID: 21764829</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Asian Continental Ancestry Group - genetics ; Biological and medical sciences ; Case-Control Studies ; Fundamental and applied biological sciences. Psychology ; Genetics of eukaryotes. Biological and molecular evolution ; Genome-Wide Association Study ; Hepatitis Antibodies - immunology ; Hepatitis B Vaccines - genetics ; Hepatitis B Vaccines - immunology ; Hepatitis B, Chronic - genetics ; Hepatitis B, Chronic - immunology ; Hepatitis B, Chronic - prevention & control ; HLA Antigens - genetics ; HLA Antigens - immunology ; Human viral diseases ; Humans ; Indonesia ; Infectious diseases ; Medical sciences ; Molecular and cellular biology ; Polymorphism, Single Nucleotide ; Viral diseases ; Viral hepatitis</subject><ispartof>Human molecular genetics, 2011-10, Vol.20 (19), p.3893-3898</ispartof><rights>The Author 2011. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com 2011</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c480t-193115a1edac9238ce49a4ce47997ba3d5d6df9a13aa68d322d2e1ab95c9a3133</citedby><cites>FETCH-LOGICAL-c480t-193115a1edac9238ce49a4ce47997ba3d5d6df9a13aa68d322d2e1ab95c9a3133</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,1583,27915,27916</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24519610$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21764829$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Png, Eileen</creatorcontrib><creatorcontrib>Thalamuthu, Anbupalam</creatorcontrib><creatorcontrib>Ong, Rick T.H.</creatorcontrib><creatorcontrib>Snippe, Harm</creatorcontrib><creatorcontrib>Boland, Greet J.</creatorcontrib><creatorcontrib>Seielstad, Mark</creatorcontrib><title>A genome-wide association study of hepatitis B vaccine response in an Indonesian population reveals multiple independent risk variants in the HLA region</title><title>Human molecular genetics</title><addtitle>Hum Mol Genet</addtitle><description>We performed a two-stage genome-wide association study (GWAS) of antibody titer in 3614 hepatitis B vaccine recipients from Indonesia's Riau Archipelago, leading to the identification of at least three independent signals within the human leukocyte antigen (HLA) complex. These appear to implicate HLA-DR [rs3135363; P= 6.53 × 10−22; odds ratio (OR) = 1.53, 95% confidence interval (CI) = 1.35-1.74]; HLA-DP, previously associated with the risk of chronic hepatitis B infection (rs9277535; P= 2.91 × 10−12; OR = 0.72, 95% CI = 0.63-0.81); and a gene rich HLA Class III interval (rs9267665; P = 1.24 × 10−17; OR = 2.05, CI = 1.64-2.57). The substantial overlap of these variants and those identified by GWAS of chronic hepatitis B infection confirms vaccine response as a model for infection, while suggesting that the vaccine is least effective in those most at risk of lifelong infection, following exposure to the virus.</description><subject>Asian Continental Ancestry Group - genetics</subject><subject>Biological and medical sciences</subject><subject>Case-Control Studies</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genetics of eukaryotes. Biological and molecular evolution</subject><subject>Genome-Wide Association Study</subject><subject>Hepatitis Antibodies - immunology</subject><subject>Hepatitis B Vaccines - genetics</subject><subject>Hepatitis B Vaccines - immunology</subject><subject>Hepatitis B, Chronic - genetics</subject><subject>Hepatitis B, Chronic - immunology</subject><subject>Hepatitis B, Chronic - prevention & control</subject><subject>HLA Antigens - genetics</subject><subject>HLA Antigens - immunology</subject><subject>Human viral diseases</subject><subject>Humans</subject><subject>Indonesia</subject><subject>Infectious diseases</subject><subject>Medical sciences</subject><subject>Molecular and cellular biology</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Viral diseases</subject><subject>Viral hepatitis</subject><issn>0964-6906</issn><issn>1460-2083</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1uEzEURi1ERUNhwwMgbxAS0rT-y2S8DBXQSpG6KevRjX0nMczYg-9MUd-Ex8VRAt3B5tqyzneu5I-xN1JcSmH11X7YXXmftVDP2EKaWlRKNPo5Wwhbm6q2oj5nL4m-CSFro1cv2LmSq9o0yi7YrzXfYUwDVj-DRw5EyQWYQoqcptk_8tTxPY7lZQrEP_IHcC5E5BlpTJGQh8gh8tvoU0QK5Tqmce6PhowPCD3xYe6nMPYH2OOIZcSJ50Dfiy6XzEQHzbRHfrNZl9SuhF-xs65k8fXpvGBfP3-6v76pNndfbq_Xm8qZRkyVtFrKJUj04KzSjUNjwZS5sna1Be2XvvadBakB6sZrpbxCCVu7dBa01PqCvT96x5x-zEhTOwRy2PcQMc3U2vKXQhmh_ks2TaONkMYU8sORdDkRZezaMYcB8mMrRXuorC2VtcfKCvz2pJ23A_q_6J-OCvDuBAA56LsM0QV64sxS2lqKJy7N478W_ga0t67M</recordid><startdate>20111001</startdate><enddate>20111001</enddate><creator>Png, Eileen</creator><creator>Thalamuthu, Anbupalam</creator><creator>Ong, Rick T.H.</creator><creator>Snippe, Harm</creator><creator>Boland, Greet J.</creator><creator>Seielstad, Mark</creator><general>Oxford University Press</general><scope>IQODW</scope><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>7X8</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20111001</creationdate><title>A genome-wide association study of hepatitis B vaccine response in an Indonesian population reveals multiple independent risk variants in the HLA region</title><author>Png, Eileen ; Thalamuthu, Anbupalam ; Ong, Rick T.H. ; Snippe, Harm ; Boland, Greet J. ; Seielstad, Mark</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c480t-193115a1edac9238ce49a4ce47997ba3d5d6df9a13aa68d322d2e1ab95c9a3133</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Asian Continental Ancestry Group - genetics</topic><topic>Biological and medical sciences</topic><topic>Case-Control Studies</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Genetics of eukaryotes. Biological and molecular evolution</topic><topic>Genome-Wide Association Study</topic><topic>Hepatitis Antibodies - immunology</topic><topic>Hepatitis B Vaccines - genetics</topic><topic>Hepatitis B Vaccines - immunology</topic><topic>Hepatitis B, Chronic - genetics</topic><topic>Hepatitis B, Chronic - immunology</topic><topic>Hepatitis B, Chronic - prevention & control</topic><topic>HLA Antigens - genetics</topic><topic>HLA Antigens - immunology</topic><topic>Human viral diseases</topic><topic>Humans</topic><topic>Indonesia</topic><topic>Infectious diseases</topic><topic>Medical sciences</topic><topic>Molecular and cellular biology</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Viral diseases</topic><topic>Viral hepatitis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Png, Eileen</creatorcontrib><creatorcontrib>Thalamuthu, Anbupalam</creatorcontrib><creatorcontrib>Ong, Rick T.H.</creatorcontrib><creatorcontrib>Snippe, Harm</creatorcontrib><creatorcontrib>Boland, Greet J.</creatorcontrib><creatorcontrib>Seielstad, Mark</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Human molecular genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Png, Eileen</au><au>Thalamuthu, Anbupalam</au><au>Ong, Rick T.H.</au><au>Snippe, Harm</au><au>Boland, Greet J.</au><au>Seielstad, Mark</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A genome-wide association study of hepatitis B vaccine response in an Indonesian population reveals multiple independent risk variants in the HLA region</atitle><jtitle>Human molecular genetics</jtitle><addtitle>Hum Mol Genet</addtitle><date>2011-10-01</date><risdate>2011</risdate><volume>20</volume><issue>19</issue><spage>3893</spage><epage>3898</epage><pages>3893-3898</pages><issn>0964-6906</issn><eissn>1460-2083</eissn><abstract>We performed a two-stage genome-wide association study (GWAS) of antibody titer in 3614 hepatitis B vaccine recipients from Indonesia's Riau Archipelago, leading to the identification of at least three independent signals within the human leukocyte antigen (HLA) complex. These appear to implicate HLA-DR [rs3135363; P= 6.53 × 10−22; odds ratio (OR) = 1.53, 95% confidence interval (CI) = 1.35-1.74]; HLA-DP, previously associated with the risk of chronic hepatitis B infection (rs9277535; P= 2.91 × 10−12; OR = 0.72, 95% CI = 0.63-0.81); and a gene rich HLA Class III interval (rs9267665; P = 1.24 × 10−17; OR = 2.05, CI = 1.64-2.57). The substantial overlap of these variants and those identified by GWAS of chronic hepatitis B infection confirms vaccine response as a model for infection, while suggesting that the vaccine is least effective in those most at risk of lifelong infection, following exposure to the virus.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>21764829</pmid><doi>10.1093/hmg/ddr302</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Oxford Journals - Connect here FIRST to enable access; Alma/SFX Local Collection; EZB Electronic Journals Library |
| subjects | Asian Continental Ancestry Group - genetics Biological and medical sciences Case-Control Studies Fundamental and applied biological sciences. Psychology Genetics of eukaryotes. Biological and molecular evolution Genome-Wide Association Study Hepatitis Antibodies - immunology Hepatitis B Vaccines - genetics Hepatitis B Vaccines - immunology Hepatitis B, Chronic - genetics Hepatitis B, Chronic - immunology Hepatitis B, Chronic - prevention & control HLA Antigens - genetics HLA Antigens - immunology Human viral diseases Humans Indonesia Infectious diseases Medical sciences Molecular and cellular biology Polymorphism, Single Nucleotide Viral diseases Viral hepatitis |
| title | A genome-wide association study of hepatitis B vaccine response in an Indonesian population reveals multiple independent risk variants in the HLA region |
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