Towards a Standard Threshold for Genome Wide Significance in Dogs

Abstract

ABSTRACT Genome‐wide association studies (GWAS) are a foundational step in tying phenotype to genotype, relying on statistical significance thresholds to distinguish true‐ from false‐positive signals of association. Dog genomics has long relied on per‐study Bonferroni thresholds of significance, basing these on SNP chip levels of markers (~100 k to > 14 M variable sites). However, as the field progresses into whole genome imputation analyses and more powerful meta‐analyses, there is a clear need to develop a standard significance threshold for common‐variant GWAS. Using 1591 dogs from the broad‐ancestry Dog10K dataset, we performed permutation analysis and developed GWAS thresholds for datasets using either 1% or 5% minor allele frequencies. The resultant p‐values, 4.2 × 10−7 and 5.0 × 10−7 respectively, are similar to previous Bonferroni levels (p‐value ~6 × 10−7), but less restrictive than the standard human p‐value, 5 × 10−8, which is sometimes used in dog studies. Given the diverse haplotypes from the > 320 breeds in the Dog10K input dataset, we suggest a p‐value of 4 × 10−7 as a standard significance threshold that could be applied to any dog GWAS.