title: The influence of population stratification on genetic markers associated with type 1 diabetes.
abstract: Ethnic admixtures may interfere with the definition of type 1 diabetes (T1D) risk determinants. The role of HLA, PTPN22, INS-VNTR, and CTLA4 in T1D predisposition was analyzed in Brazilian T1D patients (n = 915), with 81.7% self-reporting as white and 789 controls (65.6% white). The results were corrected for population stratification by genotyping 93 ancestry informative markers (AIMs) (BeadXpress platform). Ancestry composition and structural association were characterized using Structure 2.3 and STRAT. Ethnic diversity resulted in T1D determinants that were partially discordant from those reported in Caucasians and Africans. The greatest contributor to T1D was the HLA-DR3/DR4 genotype (OR = 16.5) in 23.9% of the patients, followed by -DR3/DR3 (OR = 8.9) in 8.7%, -DR4/DR4 (OR = 4.7) in 6.0% and -DR3/DR9 (OR = 4.9) in 2.6%. Correction by ancestry also confirmed that the DRB1*09-DQB1*0202 haplotype conferred susceptibility, whereas the DRB1*07-DQB1*0202 and DRB1*11-DQB1*0602 haplotypes were protective, which is similar to reports in African-American patients. By contrast, the DRB1*07-DQB1*0201 haplotype was protective in our population and in Europeans, despite conferring susceptibility to Africans. The DRB1*10-DQB1*0501 haplotype was only protective in the Brazilian population. Predisposition to T1D conferred by PTPN22 and INS-VNTR and protection against T1D conferred by the DRB1*16 allele were confirmed. Correcting for population structure is important to clarify the particular genetic variants that confer susceptibility/protection for T1D in populations with ethnic admixtures.
authors.affiliation: Laboratório de Carboidratos e Radioimunoensaio (LIM-18) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Av. Dr. Arnaldo, 455, sala 3324, 01246-903, São Paulo, São Paulo, Brazil.
authors.forename: Karla Fabiana Brasil
authors.initials: KF
authors.lastname: Gomes
authors.affiliation: Laboratório de Carboidratos e Radioimunoensaio (LIM-18) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Av. Dr. Arnaldo, 455, sala 3324, 01246-903, São Paulo, São Paulo, Brazil.
authors.forename: Aritânia Sousa
authors.initials: AS
authors.lastname: Santos
authors.affiliation: Laboratório de Carboidratos e Radioimunoensaio (LIM-18) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Av. Dr. Arnaldo, 455, sala 3324, 01246-903, São Paulo, São Paulo, Brazil.
authors.forename: Cintia
authors.initials: C
authors.lastname: Semzezem
authors.affiliation: Laboratório de Carboidratos e Radioimunoensaio (LIM-18) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Av. Dr. Arnaldo, 455, sala 3324, 01246-903, São Paulo, São Paulo, Brazil.
authors.forename: Márcia Regina
authors.initials: MR
authors.lastname: Correia
authors.affiliation: Departamento de Genética e Biologia Evolutiva, Instituto de Biociências da Universidade de São Paulo. Rua do Matão, 277, 05422-970, São Paulo, São Paulo, Brazil.
authors.forename: Luciano Abreu
authors.initials: LA
authors.lastname: Brito
authors.affiliation: Laboratório de Imunologia, Rua Claudio Manoel da Costa, 270, Marília, São Paulo, Brazil.
authors.forename: Marcelo Ortega
authors.initials: MO
authors.lastname: Ruiz
authors.affiliation: Laboratório de Carboidratos e Radioimunoensaio (LIM-18) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Av. Dr. Arnaldo, 455, sala 3324, 01246-903, São Paulo, São Paulo, Brazil.
authors.forename: Rosa Tsuneshiro
authors.initials: RT
authors.lastname: Fukui
authors.affiliation: Departamento de Genética e Biologia Evolutiva, Instituto de Biociências da Universidade de São Paulo. Rua do Matão, 277, 05422-970, São Paulo, São Paulo, Brazil.
authors.forename: Sergio Russo
authors.initials: SR
authors.lastname: Matioli
authors.affiliation: Departamento de Genética e Biologia Evolutiva, Instituto de Biociências da Universidade de São Paulo. Rua do Matão, 277, 05422-970, São Paulo, São Paulo, Brazil.
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Passos-Bueno
authors.affiliation: Laboratório de Carboidratos e Radioimunoensaio (LIM-18) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Av. Dr. Arnaldo, 455, sala 3324, 01246-903, São Paulo, São Paulo, Brazil.
authors.forename: Maria Elizabeth Rossi da
authors.initials: ME
authors.lastname: Silva
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D008297:Male; D016017:Odds Ratio; D011159:Population Surveillance; D055815:Young Adult
chemical_list: D005819:Genetic Markers; D006680:HLA Antigens