Genomic Ancestry and the Development of Diabetes in Adults in Brazil – The ELSA Study
Bruce B. Duncan1, Paula A Bracco1, Alexandre C. Pereira2,3, Maria Ines Schmidt1,
1 Postgraduate Program in Epidemiology, School of Medicine  and Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
2 Center for Clinical and Epidemiologic Research, University of São Paulo, São Paulo, Brazil.
3 Heart Institute, São Paulo, Brazil.
Background
Several studies have documented variation in the prevalence of diabetes by genomic ancestry. However, little has been reported from Latin America. Patterns of the slave trade brought African populations to Brazil that were distinct in many ways from those sent to North America. Brazilian Amerindians have a different genetic constitution than northern hemisphere Amerindians. 	 
Aims: Our objective is to characterize the relative risk of diabetes by genetic ancestry as assessed by ancestrality informative markers (AIM) in a large cohort of Brazilian adults. 
Method: ELSA-Brasil is a cohort of 15105 public servants from 6 state capitals of Brazil. We excluded the relatively few participants self-reporting Asian ancestry. Genomic ancestry was determined based on autosomal insertion/deletion AIMs. Predominant ancestry was considered present when 50% or more of an individual´s markers indicated a given ancestry. Diabetes was ascertained by self-report, use of anti-diabetic medication, abnormal fasting or 2h plasma glucose upon oral glucose tolerance testing or HbA1c> 6.5%. 
Results: The 7454 cohort participants who attended both ELSA visits, who could be characterized with respect to diabetes, who had values for all covariates, and for whom ancestrality informative markers are currently available constituted our sample. Considering all markers, 61%, 24% and 14% indicated European, African and Amerindian ancestry, respectively. Considering predominant ancestry, 69.1%, 13.3% and 4.3% of participants could be considered as European, African and Amerindian, respectively. Mean age was 51.1 years, and 1844 (24.7%) participants were ascertained to have diabetes.  Risk of diabetes among those with predominantly African, Amerindian and European ancestry, in comparison to the 995 participants with no predominant ancestry, was 25% higher (OR=1.25; 95%CI 1.03-1.52), 15% higher (OR=1.15; 95%CI 0.88-1.52) and 22% lower (OR=0.78; 95%CI 0.67-0.92), respectively. After adjustment through logistic regression for age, sex, center and socioeconomic factors possibly mediating these association, corresponding risks were 15% (OR=1.15; 95%CI 0.93-1.41) and 26% (OR=1.26; 95%CI 0.94-1.41) higher, and 17% lower (OR=0.83; 95%CI 0.70-0.98), respectively. In logistic regression analyses using as a reference 100% European genomic ancestry, for every 20% increase in African and in Amerindian ancestry, risk of diabetes increased an estimated 17% (OR=1.17; 95%CI=1.12-1.23) and 10% (OR=1.10; 95%CI=1.02-1.18), respectively.
Discussion
African and Amerindian ancestry in Brazilian adults, as determined by ancestry informative markers, confers increased risk for diabetes.

Genomic ancestry and the development of diabetes in adults in Brazil – The ELSA Study