Transmission disequilibrium as a test of linkage and association between HLA alleles and pauciarticular‐onset juvenile rheumatoid arthritis
Objective To determine if HLA class I and II alleles previously found to be associated with (or protective against) pauciarticular‐onset juvenile rheumatoid arthritis (pauci‐onset JRA) in population‐association studies are transmitted from heterozygous parents to an extent different from the expecte...
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| Veröffentlicht in: | Arthritis and rheumatism 1998-09, Vol.41 (9), p.1620-1624 |
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| container_title | Arthritis and rheumatism |
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| creator | Moroldo, Marta B. Donnelly, Patricia Saunders, Jocelyn Glass, David N. Giannini, Edward H. |
| description | Objective
To determine if HLA class I and II alleles previously found to be associated with (or protective against) pauciarticular‐onset juvenile rheumatoid arthritis (pauci‐onset JRA) in population‐association studies are transmitted from heterozygous parents to an extent different from the expected 50%.
Methods
One hundred one Caucasian North American families that had a child with pauci‐onset JRA and at least 1 parent who was heterozygous for the allele of interest were available for analysis. Both biologic parents and all children (affected and unaffected) were typed for HLA class I and II alleles. The transmission disequilibrium test (TDT) was used to determine if affected offspring received the disease‐associated (or protective) allele more (or less) frequently than its alternate allele. In families in which an unaffected sibling was available, the unmatched chi‐square test was used to determine if a meiotic segregation distortion bias existed.
Results
HLA class I alleles A2, B27, and B35 showed a significantly higher than expected frequency of transmission to affected offspring, as did class II alleles DR5 and DR8. HLA‐DR4 was found to be transmitted significantly less frequently than expected to affected, but not unaffected, offspring. All alleles that showed an excess transmission to affected offspring were transmitted to unaffected offspring at expected rates. When the data were stratified by age and sex, the likelihood of transmission of some of the alleles was strongly influenced by these variables. For example, excess transmission of HLA‐DR5 was found exclusively in female patients who were younger at the time of disease onset.
Conclusion
Results from these family‐based studies rule out the possibility that HLA disease associations found in earlier studies were a result of population stratification and establish linkage and association between the major histocompatibility complex and pauci‐onset JRA. |
| doi_str_mv | 10.1002/1529-0131(199809)41:9<1620::AID-ART12>3.0.CO;2-L |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_73935649</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>73935649</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3712-3716728601510a910531b740f834c9c3fcc509ed3aece5b7238374d55ec2db6b3</originalsourceid><addsrcrecordid>eNqVkc1u1DAUhS0EKtPCIyB5gRAsMvgnTuIBIY2Gn1aKNKga1pbj3FAXJ5naCVV3fQEknpEnwWlGs2LDxpZ9j4_vPR9CBSVLSgh7SwWTCaGcvqZSFkS-SelKvqcZI6vV-uJjsr7cUfaBL8lys33HkvIRWhyfPEYLQkiacCHpU3QawnU8Mi74CTqRuaBEpgv0a-d1F1obgu07XNsAN6N1tvJ2bLEOWOMBwoD7Bjvb_dDfAeuujoXQG6uH6U0Fwy1Ah8_LNdbOgYPwoNnrMUr8YM3otP9z_7vvAgz4evwJnXWA_RWMrR56G-38cOXtYMMz9KTRLsDzw36Gvn3-tNucJ-X2y8VmXSaG55QlcclyVmSExim0pERwWuUpaQqeGml4Y4wgEmquwYCocsYLnqe1EGBYXWUVP0OvZt-972_GOKCKCRhwTnfQj0HlXHKRpTIKv85C4_sQPDRq722r_Z2iRE2E1BS3muJWMyGVUiXVREipSEg9EFJcEbXZKqbKaPni8PdYtVAfDQ9IYv3loa6D0a6JfIwNRxnjuSzyLMouZ9ltDPPuf9r6V1fzBf8LvUW5Pg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>73935649</pqid></control><display><type>article</type><title>Transmission disequilibrium as a test of linkage and association between HLA alleles and pauciarticular‐onset juvenile rheumatoid arthritis</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Alma/SFX Local Collection</source><creator>Moroldo, Marta B. ; Donnelly, Patricia ; Saunders, Jocelyn ; Glass, David N. ; Giannini, Edward H.</creator><creatorcontrib>Moroldo, Marta B. ; Donnelly, Patricia ; Saunders, Jocelyn ; Glass, David N. ; Giannini, Edward H.</creatorcontrib><description>Objective
To determine if HLA class I and II alleles previously found to be associated with (or protective against) pauciarticular‐onset juvenile rheumatoid arthritis (pauci‐onset JRA) in population‐association studies are transmitted from heterozygous parents to an extent different from the expected 50%.
Methods
One hundred one Caucasian North American families that had a child with pauci‐onset JRA and at least 1 parent who was heterozygous for the allele of interest were available for analysis. Both biologic parents and all children (affected and unaffected) were typed for HLA class I and II alleles. The transmission disequilibrium test (TDT) was used to determine if affected offspring received the disease‐associated (or protective) allele more (or less) frequently than its alternate allele. In families in which an unaffected sibling was available, the unmatched chi‐square test was used to determine if a meiotic segregation distortion bias existed.
Results
HLA class I alleles A2, B27, and B35 showed a significantly higher than expected frequency of transmission to affected offspring, as did class II alleles DR5 and DR8. HLA‐DR4 was found to be transmitted significantly less frequently than expected to affected, but not unaffected, offspring. All alleles that showed an excess transmission to affected offspring were transmitted to unaffected offspring at expected rates. When the data were stratified by age and sex, the likelihood of transmission of some of the alleles was strongly influenced by these variables. For example, excess transmission of HLA‐DR5 was found exclusively in female patients who were younger at the time of disease onset.
Conclusion
Results from these family‐based studies rule out the possibility that HLA disease associations found in earlier studies were a result of population stratification and establish linkage and association between the major histocompatibility complex and pauci‐onset JRA.</description><identifier>ISSN: 0004-3591</identifier><identifier>EISSN: 1529-0131</identifier><identifier>DOI: 10.1002/1529-0131(199809)41:9<1620::AID-ART12>3.0.CO;2-L</identifier><identifier>PMID: 9751094</identifier><identifier>CODEN: ARHEAW</identifier><language>eng</language><publisher>New York: John Wiley & Sons, Inc</publisher><subject>Adolescent ; Adult ; Alleles ; Arthritis, Juvenile - genetics ; Arthritis, Juvenile - pathology ; Biological and medical sciences ; Child ; Child, Preschool ; Diseases of the osteoarticular system ; Female ; Genetic Heterogeneity ; Histocompatibility Testing ; HLA Antigens - genetics ; Humans ; Infant ; Infant, Newborn ; Inflammatory joint diseases ; Linkage Disequilibrium - genetics ; Male ; Medical sciences</subject><ispartof>Arthritis and rheumatism, 1998-09, Vol.41 (9), p.1620-1624</ispartof><rights>Copyright © 1998 by the American College of Rheumatology</rights><rights>1998 INIST-CNRS</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c3712-3716728601510a910531b740f834c9c3fcc509ed3aece5b7238374d55ec2db6b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2F1529-0131%28199809%2941%3A9%3C1620%3A%3AAID-ART12%3E3.0.CO%3B2-L$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2F1529-0131%28199809%2941%3A9%3C1620%3A%3AAID-ART12%3E3.0.CO%3B2-L$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2379876$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9751094$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Moroldo, Marta B.</creatorcontrib><creatorcontrib>Donnelly, Patricia</creatorcontrib><creatorcontrib>Saunders, Jocelyn</creatorcontrib><creatorcontrib>Glass, David N.</creatorcontrib><creatorcontrib>Giannini, Edward H.</creatorcontrib><title>Transmission disequilibrium as a test of linkage and association between HLA alleles and pauciarticular‐onset juvenile rheumatoid arthritis</title><title>Arthritis and rheumatism</title><addtitle>Arthritis Rheum</addtitle><description>Objective
To determine if HLA class I and II alleles previously found to be associated with (or protective against) pauciarticular‐onset juvenile rheumatoid arthritis (pauci‐onset JRA) in population‐association studies are transmitted from heterozygous parents to an extent different from the expected 50%.
Methods
One hundred one Caucasian North American families that had a child with pauci‐onset JRA and at least 1 parent who was heterozygous for the allele of interest were available for analysis. Both biologic parents and all children (affected and unaffected) were typed for HLA class I and II alleles. The transmission disequilibrium test (TDT) was used to determine if affected offspring received the disease‐associated (or protective) allele more (or less) frequently than its alternate allele. In families in which an unaffected sibling was available, the unmatched chi‐square test was used to determine if a meiotic segregation distortion bias existed.
Results
HLA class I alleles A2, B27, and B35 showed a significantly higher than expected frequency of transmission to affected offspring, as did class II alleles DR5 and DR8. HLA‐DR4 was found to be transmitted significantly less frequently than expected to affected, but not unaffected, offspring. All alleles that showed an excess transmission to affected offspring were transmitted to unaffected offspring at expected rates. When the data were stratified by age and sex, the likelihood of transmission of some of the alleles was strongly influenced by these variables. For example, excess transmission of HLA‐DR5 was found exclusively in female patients who were younger at the time of disease onset.
Conclusion
Results from these family‐based studies rule out the possibility that HLA disease associations found in earlier studies were a result of population stratification and establish linkage and association between the major histocompatibility complex and pauci‐onset JRA.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Alleles</subject><subject>Arthritis, Juvenile - genetics</subject><subject>Arthritis, Juvenile - pathology</subject><subject>Biological and medical sciences</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Diseases of the osteoarticular system</subject><subject>Female</subject><subject>Genetic Heterogeneity</subject><subject>Histocompatibility Testing</subject><subject>HLA Antigens - genetics</subject><subject>Humans</subject><subject>Infant</subject><subject>Infant, Newborn</subject><subject>Inflammatory joint diseases</subject><subject>Linkage Disequilibrium - genetics</subject><subject>Male</subject><subject>Medical sciences</subject><issn>0004-3591</issn><issn>1529-0131</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVkc1u1DAUhS0EKtPCIyB5gRAsMvgnTuIBIY2Gn1aKNKga1pbj3FAXJ5naCVV3fQEknpEnwWlGs2LDxpZ9j4_vPR9CBSVLSgh7SwWTCaGcvqZSFkS-SelKvqcZI6vV-uJjsr7cUfaBL8lys33HkvIRWhyfPEYLQkiacCHpU3QawnU8Mi74CTqRuaBEpgv0a-d1F1obgu07XNsAN6N1tvJ2bLEOWOMBwoD7Bjvb_dDfAeuujoXQG6uH6U0Fwy1Ah8_LNdbOgYPwoNnrMUr8YM3otP9z_7vvAgz4evwJnXWA_RWMrR56G-38cOXtYMMz9KTRLsDzw36Gvn3-tNucJ-X2y8VmXSaG55QlcclyVmSExim0pERwWuUpaQqeGml4Y4wgEmquwYCocsYLnqe1EGBYXWUVP0OvZt-972_GOKCKCRhwTnfQj0HlXHKRpTIKv85C4_sQPDRq722r_Z2iRE2E1BS3muJWMyGVUiXVREipSEg9EFJcEbXZKqbKaPni8PdYtVAfDQ9IYv3loa6D0a6JfIwNRxnjuSzyLMouZ9ltDPPuf9r6V1fzBf8LvUW5Pg</recordid><startdate>199809</startdate><enddate>199809</enddate><creator>Moroldo, Marta B.</creator><creator>Donnelly, Patricia</creator><creator>Saunders, Jocelyn</creator><creator>Glass, David N.</creator><creator>Giannini, Edward H.</creator><general>John Wiley & Sons, Inc</general><general>Wiley</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></search><sort><creationdate>199809</creationdate><title>Transmission disequilibrium as a test of linkage and association between HLA alleles and pauciarticular‐onset juvenile rheumatoid arthritis</title><author>Moroldo, Marta B. ; Donnelly, Patricia ; Saunders, Jocelyn ; Glass, David N. ; Giannini, Edward H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3712-3716728601510a910531b740f834c9c3fcc509ed3aece5b7238374d55ec2db6b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Alleles</topic><topic>Arthritis, Juvenile - genetics</topic><topic>Arthritis, Juvenile - pathology</topic><topic>Biological and medical sciences</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Diseases of the osteoarticular system</topic><topic>Female</topic><topic>Genetic Heterogeneity</topic><topic>Histocompatibility Testing</topic><topic>HLA Antigens - genetics</topic><topic>Humans</topic><topic>Infant</topic><topic>Infant, Newborn</topic><topic>Inflammatory joint diseases</topic><topic>Linkage Disequilibrium - genetics</topic><topic>Male</topic><topic>Medical sciences</topic><toplevel>online_resources</toplevel><creatorcontrib>Moroldo, Marta B.</creatorcontrib><creatorcontrib>Donnelly, Patricia</creatorcontrib><creatorcontrib>Saunders, Jocelyn</creatorcontrib><creatorcontrib>Glass, David N.</creatorcontrib><creatorcontrib>Giannini, Edward H.</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><jtitle>Arthritis and rheumatism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Moroldo, Marta B.</au><au>Donnelly, Patricia</au><au>Saunders, Jocelyn</au><au>Glass, David N.</au><au>Giannini, Edward H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transmission disequilibrium as a test of linkage and association between HLA alleles and pauciarticular‐onset juvenile rheumatoid arthritis</atitle><jtitle>Arthritis and rheumatism</jtitle><addtitle>Arthritis Rheum</addtitle><date>1998-09</date><risdate>1998</risdate><volume>41</volume><issue>9</issue><spage>1620</spage><epage>1624</epage><pages>1620-1624</pages><issn>0004-3591</issn><eissn>1529-0131</eissn><coden>ARHEAW</coden><abstract>Objective
To determine if HLA class I and II alleles previously found to be associated with (or protective against) pauciarticular‐onset juvenile rheumatoid arthritis (pauci‐onset JRA) in population‐association studies are transmitted from heterozygous parents to an extent different from the expected 50%.
Methods
One hundred one Caucasian North American families that had a child with pauci‐onset JRA and at least 1 parent who was heterozygous for the allele of interest were available for analysis. Both biologic parents and all children (affected and unaffected) were typed for HLA class I and II alleles. The transmission disequilibrium test (TDT) was used to determine if affected offspring received the disease‐associated (or protective) allele more (or less) frequently than its alternate allele. In families in which an unaffected sibling was available, the unmatched chi‐square test was used to determine if a meiotic segregation distortion bias existed.
Results
HLA class I alleles A2, B27, and B35 showed a significantly higher than expected frequency of transmission to affected offspring, as did class II alleles DR5 and DR8. HLA‐DR4 was found to be transmitted significantly less frequently than expected to affected, but not unaffected, offspring. All alleles that showed an excess transmission to affected offspring were transmitted to unaffected offspring at expected rates. When the data were stratified by age and sex, the likelihood of transmission of some of the alleles was strongly influenced by these variables. For example, excess transmission of HLA‐DR5 was found exclusively in female patients who were younger at the time of disease onset.
Conclusion
Results from these family‐based studies rule out the possibility that HLA disease associations found in earlier studies were a result of population stratification and establish linkage and association between the major histocompatibility complex and pauci‐onset JRA.</abstract><cop>New York</cop><pub>John Wiley & Sons, Inc</pub><pmid>9751094</pmid><doi>10.1002/1529-0131(199809)41:9<1620::AID-ART12>3.0.CO;2-L</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Arthritis and rheumatism, 1998-09, Vol.41 (9), p.1620-1624 |
| issn | 0004-3591 1529-0131 |
| language | eng |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Alma/SFX Local Collection |
| subjects | Adolescent Adult Alleles Arthritis, Juvenile - genetics Arthritis, Juvenile - pathology Biological and medical sciences Child Child, Preschool Diseases of the osteoarticular system Female Genetic Heterogeneity Histocompatibility Testing HLA Antigens - genetics Humans Infant Infant, Newborn Inflammatory joint diseases Linkage Disequilibrium - genetics Male Medical sciences |
| title | Transmission disequilibrium as a test of linkage and association between HLA alleles and pauciarticular‐onset juvenile rheumatoid arthritis |
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