Genetic basis of resistance to avian influenza in different commercial varieties of layer chickens.

An outbreak of H5N2 highly pathogenic avian influenza (HPAI) in 2015, resulting in mandatory euthanization of millions of chickens, was one of the most fatal in the US history. The aim of this study was to detect genes associated with survival following natural infection with HPAI during this outbreak. Blood samples were collected from 274 individuals from 3 commercial varieties of White Leghorn. Survivors and age and genetics matched non-affected controls from each variety were included in the comparison. All individuals were genotyped on the 600k SNP array. A genome-wide association study (GWAS) with the standard frequency test in PLINK was performed within each variety, whereas logistic regression with the first 3 multidimensional scaling components as covariates was used for joined analysis of all varieties. Several SNPs located within 3 regions reached the 5% Bonferroni genome-wide threshold of significance (P < 3.87E-06). The associations were identified for 2 varieties and only within genetic variety on chromosomes 11 (variety 1), 5, and 18 (variety 3). A genome-wide scan with FST was also performed for 40, 100, and 500 kb windows to support the genome-wide association analyses. The regions with highest FST values between cases and controls were located on chromosomes 1 and Z, and overlapped a number of genes with immunological function and QTL connected to health. Only a few regions were consistent between the analyses, and were significant in the FST genome-wide scan and approaching significance in GWAS. This study confirms that resistance to HPAI is a complex, polygenic trait and that mechanisms of resistance may be population specific. Further study utilizing much larger sample sizes and/or sequence data is needed to detect genes responsible for HPAI survival.