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Independent replication and initial fine mapping of 3p21-24 in Asperger syndrome.

ABSTRACT: BACKGROUND: Asperger syndrome is characterised by abnormalities in social interaction as well as repetitive and stereotyped behaviours and interests. The trait is thought to display complex inheritance, but in a subset of families the inheritance resembles the autosomal dominant model. Linkage to 3p14-24 has recently been reported in Asperger syndrome in Finnish families with a maximum multipoint NPL(all) of 3.32 at D3S2432. METHODS: We have replicated linkage findings to 3p21-24 in 12 new extended Asperger syndrome families. Linkage analyses were performed separately for the 12 new families, and linkage and association analyses were also performed jointly with data from the original genome-wide screen. RESULTS: Best two point and multipoint logarithm of the odds (LOD) scores in analyses of both data sets were obtained at D3S2432 (NPL(all) = 3.83) with both subsets of families contributing to linkage. Association analysis of the combined data set produced a trend towards association with D3S2432 and D3S1619. CONCLUSIONS: This study further validates 3q21-24 as a candidate region for Asperger syndrome.

SUBMITTER: Rehnstrom K

PROVIDER: S-EPMC2564646 | biostudies-literature | 2006 Feb

REPOSITORIES: biostudies-literature

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Independent replication and initial fine mapping of 3p21-24 in Asperger syndrome.

Rehnström K K Ylisaukko-oja T T Nieminen-von Wendt T T Sarenius S S Källman T T Kempas E E von Wendt L L Peltonen L L Järvelä I I

Journal of medical genetics 20060201 2

<h4>Background</h4>Asperger syndrome is characterised by abnormalities in social interaction as well as repetitive and stereotyped behaviours and interests. The trait is thought to display complex inheritance, but in a subset of families the inheritance resembles the autosomal dominant model. Linkage to 3p14-24 has recently been reported in Asperger syndrome in Finnish families with a maximum multipoint NPL(all) of 3.32 at D3S2432.<h4>Methods</h4>We have replicated linkage findings to 3p21-24 in ...[more]

PMID: 16467216

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Project description:Background & aimsAssociation studies have greatly refined the important role of the major histocompatibility complex (MHC) region in autoimmune hepatitis (AIH). However, the effects of human leucocyte antigen (HLA) polymorphisms on AIH are not well established. The aim of this study is to systematically characterise the association of MHC variants with AIH in our well-defined cohort of patients.MethodsWe performed an imputation-based analysis on the extensive association observed within the MHC region using the Han-MHC reference panel, and tested the comprehensive associations of HLA polymorphisms with AIH in 1622 Chinese AIH type 1 patients and 10,466 population controls.ResultsA total of 588 HLA variants were significantly associated with AIH, with HLA-B∗35:01 (p = 8.17 × 10-304; odds ratio [OR] = 7.32) contributing the strongest signal. Stepwise conditional analysis revealed additional independent signals at HLA-B∗08:01 (p = 1.35 × 10-33; OR = 4.26) and rs7765379 (p = 5.08 × 10-18; OR = 1.66). A strong link between the lead HLA variant and clinical phenotypes of AIH was observed: patients with HLA-B∗35:01 were less frequently positive for ANA and tended to have higher serum AST and ALT levels at diagnosis, but lower serum IgG levels.ConclusionsOur study reveals three novel and independent variants at HLA-B∗35:01, HLA-B∗08:01, and rs7765379 associated with AIH across the whole MHC region in the Han Chinese population. The findings illustrate the value of the MHC region in AIH and provide a new perspective for the immunogenetics of AIH.Impact and implicationsThis study revealed three novel and independent variants associated with autoimmune hepatitis across the whole major histocompatibility complex region in the Han Chinese population. These findings are significant in identifying autoantigens, providing insights into the activation of the autoimmune processes, and further advancing our understanding of the immunogenetic basis underlying autoimmune hepatitis.

Dataset Information

Independent replication and initial fine mapping of 3p21-24 in Asperger syndrome.

Publications

Independent replication and initial fine mapping of 3p21-24 in Asperger syndrome.

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