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ZNF248 Is Associated with Elder-Onset Asthma in African Americans
Sunday, March 6, 2016
South Exhibit Hall H (Convention Center)
Leyao Wang, Yasmmyn D. Salinas, Andrew T. DeWan

Rationale: There is a lack of knowledge of elder-onset asthma (EOA), especially regarding African Americans. Identification of risk genes for EOA will help elucidate the underlying molecular mechanisms and promote diagnostic and therapeutic strategies.

Methods: Data from the Women’s Health Initiative (WHI), consisting of 1 baseline exam (1993-1998) and 6 follow-up exams (2001-2006), were used to detect EOA among African American women aged 50-79 years. EOA cases are defined as subjects who were asthma-free at baseline and were diagnosed with asthma in a follow-up exam. Controls are those who completed all exams and never had an asthma diagnosis. The association between risk factors, such as obesity and smoking, and asthma was evaluated. Genome-wide association analysis adjusted for age, body mass index and smoking was conducted and SNP p-values were used for a gene-based analysis. Significant candidate genes were replicated in the African American subjects of the Multi-Ethnic Study of Atherosclerosis (MESA; n=38 cases, n=826 controls).

Results: 381 incident asthma cases and 1204 controls were identified in WHI. Subjects with overweight/obese had a higher risk of developing EOA compared to subjects with normal weight (odds ratio (OR) = 1.95, 95% confidence interval (CI): 1.42, 2.67). Ever-smokers had a higher risk of being EOA compared to never smokers (OR=1.40, 95%CI: 1.11, 1.77). The gene zinc finger protein 248 (ZNF248) was genome-wide significant in the gene-based analysis (p-value < 1×10-6) and the association replicated in MESA (p=0.015).

Conclusions: Obesity and smoking are risk factors for EOA in African Americans. ZNF248 is a novel candidate gene for asthma.