title: Association between type 1 diabetes age of onset and HLA among sibling pairs.
abstract: In this study, we report type 1 diabetes age-of-onset association with HLA class II (DRB1, DQB1, and DPB1) and class I (A) genes in 222 multiplex families from the Human Biological Data Interchange. Linear regression showed a small (R2 = 0.26) but significant correlation in the ages of onset among sib pairs. A strong association in age of onset between members of sib pairs was observed when the analysis was performed using contingency tables that split sibs into three age-at-onset ranges (0-10, 11-20, and 21-36 years). The association is strongest for sib pairs that share both haplotypes and is nonsignificant for sib pairs that do not share any DR-DQ haplotypes. A goodness-of-fit test revealed that DR-DQ haplotype sharing cannot account for all the association in age of onset among sib pairs. The age-of-onset distribution of DR-DQ haplotypes is affected by the DPB1 and A alleles present. The strongest associations were found with the A locus: DR3/DR4 genotype frequency decreases with age of onset in this data set only among A*0101- individuals, and A*2402 is strongly associated with younger age of onset in many DR-DQ haplotypes.
authors.affiliation: Department of Integrative Biology, University of California, Berkeley, USA. anamaria_v_valdes@sbphrd.com
authors.forename: A M
authors.initials: AM
authors.lastname: Valdes
authors.forename: G
authors.initials: G
authors.lastname: Thomson
authors.forename: H A
authors.initials: HA
authors.lastname: Erlich
authors.forename: J A
authors.initials: JA
authors.lastname: Noble
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*; D006680:HLA Antigens / Q000032:analysis*; D006683:HLA-DQ Antigens / Q000032:analysis; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000032:analysis; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D007223:Infant; D007231:Infant, Newborn
chemical_list: D006680:HLA Antigens; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II