Genomic ancestry and the social pathways leading to major depression in adulthood: the mediating effect of socioeconomic position and discrimination.
Evidence suggests that there is an association between ethnicity/skin color and depression; however, many contextual and individual variables, like sense of discrimination and socioeconomic position (SEP), might influence the direction of this association. We assessed the association between African ancestry and major depression among young adults that have been followed-up since birth in a Southern Brazilian city, and the mediating effect of SEP and discrimination.



In 1982, all hospital deliveries in Pelotas (Southern Brazil) were identified; liveborns were examined and their mothers interviewed (n = 5914). In 2012-13, at 30 years of age, we used the Mini International Neuropsychiatric Interview (MINI) for major depression diagnosis. In addition, DNA samples were genotyped for approximately 2.5 million single nucleotide polymorphisms (SNPs) using Illumina (CA, USA) HumanOmni2.5-8v1 array. Genomic ancestry estimation was based on approximately 370 000 single nucleotide polymorphisms (SNPs) mutually available for the Pelotas cohort and selected samples (used as reference panels) of the HapMap and Human Genome Diversity (HGDP). We estimated prevalence ratios (PR) using Poisson regression models and evaluated the association between percentage of African ancestry and major depression. We used G-computation for mediation analysis.



At 30 years, 3576 individuals were evaluated for major depression (prevalence = 7.9 %). Only individuals in the highest SEP, who had a percentage of African ancestry between >5-30 % and >30 % had a prevalence of major depression 2.16 (PR = 2.16 95 % CI [1.05-4.45]) and 2.74 (PR = 2.74 95 % CI [1.06-7.06]) times higher, than those with 5 % or less, respectively. Among these subjects, sense of discrimination by skin color, captured 84 % of the association between African ancestry and major depression.



SEP is an important effect modifier of the positive association between African ancestry and major depression. In addition, this association is predominantly mediated by the sense of feeling discriminated by skin color.
Postgraduate Program in Epidemiology, Federal University of Pelotas, Rua Marechal Deodoro, 1160 - 3° Piso, Bairro Centro. Cep: 96020-220, Caixa Postal 464, Pelotas, RS, Brazil. chlmz@yahoo.com.
Christian
C
Loret de Mola
Postgraduate Program in Epidemiology, Federal University of Pelotas, Rua Marechal Deodoro, 1160 - 3° Piso, Bairro Centro. Cep: 96020-220, Caixa Postal 464, Pelotas, RS, Brazil.
Fernando Pires
FP
Hartwig
Postgraduate Program in Epidemiology, Federal University of Pelotas, Rua Marechal Deodoro, 1160 - 3° Piso, Bairro Centro. Cep: 96020-220, Caixa Postal 464, Pelotas, RS, Brazil.
Helen
H
Gonçalves
Health and Behavior Postgraduate Program, Universidade Católica de Pelotas - UCPEL, Rua Gonçalves Chaves, 377 - sala 411, prédio C. CEP: 96015-560, Pelotas, RS, Brazil.
Luciana de Avila
Lde A
Quevedo
Health and Behavior Postgraduate Program, Universidade Católica de Pelotas - UCPEL, Rua Gonçalves Chaves, 377 - sala 411, prédio C. CEP: 96015-560, Pelotas, RS, Brazil.
Ricardo
R
Pinheiro
Postgraduate Program in Epidemiology, Federal University of Pelotas, Rua Marechal Deodoro, 1160 - 3° Piso, Bairro Centro. Cep: 96020-220, Caixa Postal 464, Pelotas, RS, Brazil.
Denise Petrucci
DP
Gigante
Postgraduate Program in Epidemiology, Federal University of Pelotas, Rua Marechal Deodoro, 1160 - 3° Piso, Bairro Centro. Cep: 96020-220, Caixa Postal 464, Pelotas, RS, Brazil.|Health and Behavior Postgraduate Program, Universidade Católica de Pelotas - UCPEL, Rua Gonçalves Chaves, 377 - sala 411, prédio C. CEP: 96015-560, Pelotas, RS, Brazil.
Janaína Vieira Dos Santos
JV
Motta
Heart Institute, University of São Paulo Medical School, Av. Dr. Arnaldo, 455 - Cerqueira César - CEP: 01246903, São Paulo, SP, Brazil.
Alexandre C
AC
Pereira
Health and Behavior Postgraduate Program, Universidade Católica de Pelotas - UCPEL, Rua Gonçalves Chaves, 377 - sala 411, prédio C. CEP: 96015-560, Pelotas, RS, Brazil.
Fernando C
FC
Barros
Postgraduate Program in Epidemiology, Federal University of Pelotas, Rua Marechal Deodoro, 1160 - 3° Piso, Bairro Centro. Cep: 96020-220, Caixa Postal 464, Pelotas, RS, Brazil.
Bernardo Lessa
BL
Horta
D000328:Adult; D044383:Black People / Q000235:genetics*; D001938:Brazil; D003865:Major Depressive Disorder / Q000208:ethnology* / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D015995:Prevalence; D011569:Psychiatric Status Rating Scales; D055815:Young Adult
Brazil; Cohort; Discrimination; Genomic ancestry; Major depression; Socioeconomic position