Transferability of genome-wide associated loci for asthma in African Americans

ABSTRACT

Objective: Transferability of significantly associated loci or GWAS “hits” adds credibility to genotype-disease associations and provides evidence for generalizability across different ancestral populations. We sought evidence of association of known asthma-associated single nucleotide polymorphisms (SNPs) in an African American population. Methods: Subjects comprised 661 participants (261 asthma cases and 400 controls) from the Howard University Family Study. Forty-eight SNPs previously reported to be associated with asthma by GWAS were selected for testing. We adopted a combined strategy by first adopting an “exact” approach where we looked-up only the reported index SNP. For those index SNPs missing form our dataset, we used a “local” approach that examined all the regional SNPs in LD with the index SNP. Results: Out of the 48 SNPs, our cohort had genotype data available for 27, which were examined for exact replication. Of these, two SNPs were found positively associated with asthma. These included: rs10508372 (OR = 1.567 [95%CI, 1.133-2.167], P = 0.0066) and rs2378383 (OR = 2.147 [95%CI, 1.149–4.013], P = 0.0166), located on chromosomal bands 10p14 and 9q21.31, respectively. Local replication of the remaining 21 loci showed association at two chromosomal loci (9p24.1-rs2381413 and 6p21.32-rs3132947; Bonferroni-corrected P values: 0.0033 and 0.0197, respectively). Of note, multiple SNPs in LD with rs2381413 located upstream of IL33 were significantly associated with asthma. Conclusions: This study has successfully transferred four reported asthma-associated loci in an independent African American population. Identification of several asthma-associated SNPs in the upstream of the IL33, a gene previously implicated in allergic inflammation of asthmatic airway, supports the generalizability of this finding.

KEYWORDS:

• Asthma
• replication
• single nucleotide polymorphism
• genetic association
• African Americans
• IL33
• ethnicity

Acknowledgments

The authors would like to thank participants, physicians, and investigators in the HUFS.

Declaration of interest

The authors report no conflicts of interest.

Funding

The Howard University Family Study (HUFS) was supported by grants S06GM008016-320107 to C.N.R. and S06GM008016–380111 to A.A.A., both from the MBRS/SCORE Program of the National Institute of General Medical Sciences, National Institutes of Health (NIH). Participant enrollment for the HUFS was carried out at the Howard University General Clinical Research Center, which is supported by grant 2M01RR010284 from the National Center for Research Resources (NCRR), NIH. This research was supported in part by the RCMI Program at Howard University funded by the Division of Research Infrastructure, NCRR, NIH (RR003048) and by the Intramural Research Program of the Center for Research on Genomics and Global Health (CRGGH). The CRGGH is supported by the National Human Genome Research Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the Center for Information Technology, and the Office of the Director at the NIH (Z01HG200362).