Genomic Regions 10q22.2, 17q21.31, and 2p23.1 Can Contribute to a Lower Lung Function in African Descent Populations

Abstract

Accumulated evidence supports the contribution of genetic factors in modulating airway function, especially ancestry. We investigated whether genetic polymorphisms can affect lung function in a mixed Brazilian child population using the admixture mapping strategy through RFMix software version 1.5.4 (Stanford University, Stanford, CA, USA), followed by fine mapping, to identify regions whereby local African or European ancestry is associated with lung function measured by the forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC) ratio, an indicator of airway obstruction. The research cohort included 958 individuals aged 4 to 11 years enrolled in the SCAALA (Social Change, Asthma, Allergy in Latin America) Program. We identified that African ancestry at 17q21.31, 10q22.2, and 2p23.1 regions was associated with lower lung function measured by FEV1/FVC p < 1.9 × 10−4. In contrast, European ancestry at 17q21.31 showed an opposite effect. Fine mapping pointed out 5 single nucleotide polymorphisms (SNPs) also associated in our replication cohort (rs10999948, rs373831475, rs8068257, rs6744555, and rs1520322). Our results suggest that genomic regions associated with ancestry may contribute to differences in lung function measurements in African American children in Brazil replicated in a cohort of Brazilian adults. The analysis strategy used in this work is especially important for phenotypes, such as lung function, which has considerable disparities in terms of measurements across different populations.

A review of ancestrality and admixture in Latin America and the caribbean focusing on native American and African descendant populations

“…Indeed, one study from 958 children of the Social Change, Asthma, Allergy in Latin America (SCAALA) Cohort in Salvador, Brazil, showed that African ancestry at the 17q21.31, 10q22.2, and 2p23.1 loci was associated with lower lung function. In contrast, the European ancestry at the 17q21.31 locus showed the opposite effect ( Fonseca et al, 2020 ).…”

Understanding and controlling asthma in Latin America: A review of recent research informed by the SCAALA programme

“… 116 Using the same GWAS, variants in the 17q12‐21 locus were analysed, and among these, three on OMRDL3 and one on TOP2A gene were associated with childhood asthma. 126 …”

“…Admixture mapping of Brazilian children identified that African ancestry at the loci 17q21.31, 10q22.2, and 2p23.1 were associated with lower lung function. 126 Further, equations for predicting lung function in children, based on genetic ancestry have proven to be more accurate than standard models that use ethnic‐racial classification. 142 The observation in Brazil that African ancestry was negatively associated with maternal education and household income and positively associated with infections 127 indicates the need for caution in interpreting significant associations of African ancestry with a disease as being indicative of genetic rather than social and environmental factors.…”

“…Further polymorphisms in both genes affected gene expression levels and DAD1 was over‐expressed in asthmatics 116 . Using the same GWAS, variants in the 17q12‐21 locus were analysed, and among these, three on OMRDL3 and one on TOP2A gene were associated with childhood asthma 126 …”

“…This analysis also indicated that multiple ancestry‐informative noncoding variants upstream of SMAD2 might have a role in asthma susceptibility. Admixture mapping of Brazilian children identified that African ancestry at the loci 17q21.31, 10q22.2, and 2p23.1 were associated with lower lung function 126 . Further, equations for predicting lung function in children, based on genetic ancestry have proven to be more accurate than standard models that use ethnic‐racial classification 142 .…”