Variants in the β-globin locus are associated with pneumonia in African American children

Area of Science:

• Genetics
• Pediatrics
• Pulmonology

Background:

• The rs334 variant (A allele) in the beta-globin gene is a significant genetic predictor of pneumonia in African American adults, strongly associated with sickle cell disease (SCD).
• No similar genetic studies on pneumonia risk have been conducted in African American children.

Purpose of the Study:

• To identify genetic predictors of pneumonia in African American children.
• To compare the effectiveness of different genetic imputation panels (1000 Genomes and TOPMed) in identifying these predictors.

Main Methods:

• Genome-wide association analyses were performed on 482 African American children with pneumonia and 2,048 controls.
• Genotypes were imputed using the 1000 Genomes (1KG) and TOPMed reference panels.
• Statistical analyses included calculating odds ratios (OR) and confidence intervals (CI) for associated genetic variants.

Main Results:

• Using 1KG imputed genotypes, rs334 (A allele) was the most significant variant (OR = 2.76).
• Using TOPMed imputed genotypes, rs2226952 in the beta-globin locus control region (G allele) was most significant (OR = 2.14).
• After conditioning on rs334, rs33930165 (T allele) showed strong association (1KG OR = 4.09; TOPMed OR = 3.58), and can cause SCD in compound heterozygotes.

Conclusions:

• Genetic determinants of pneumonia in African American children are strongly linked to factors increasing the risk of sickle cell disease (SCD).
• The study developed a method to estimate the power of different sample sets for genetic analyses.