DOI: 10.5061/dryad.3j9kd51r2
title: Data from: A variant in the 5′UTR of ERBB4 is associated with lifespan in Golden Retrievers

description: Genome-wide association studies (GWAS) in long-lived human populations
 have led to identification of variants associated with Alzheimer’s disease
 and cardiovascular disease, the latter being the most common cause of
 mortality in people worldwide. In contrast, naturally occurring cancer
 represents the leading cause of death in pet dogs, and specific breeds
 like the Golden Retriever (GR) carry up to a 65% cancer-related death
 rate. We hypothesized that GWAS of long-lived GRs might lead to the
 identification of genetic variants capable of modifying longevity within
 this cancer-predisposed breed. A GWAS was performed comparing GR
 dogs ≥ 14 years to dogs dying prior to age 12 which revealed a
 significant association to ERBB4, the only member of the epidermal growth
 factor receptor family capable of serving as both a tumor suppressor gene
 and an oncogene. No coding variants were identified, however, distinct
 haplotypes in the 5′UTR were associated with reduced lifespan in two
 separate populations of GR dogs. When all GR dogs were analyzed together
 (n = 304), the presence of haplotype 3 was associated with shorter
 survival (11.8 years vs. 12.8 years, p = 0.024). GRs
 homozygous for haplotype 3 had the shortest survival, and GRs homozygous
 for haplotype 1 had the longest survival (11.6 years vs.
 13.5 years, p = 0.0008). Sub-analyses revealed that the
 difference in lifespan for GRs carrying at least 1 copy of haplotype 3 was
 specific to female dogs (p = 0.009), whereas survival remained
 significantly different in both male and female GRs homozygous for
 haplotype 1 or haplotype 3 (p = 0.026 and p = 0.009, respectively). Taken
 together, these findings implicate a potential role for ERBB4 in GR
 longevity and provide evidence that within-breed canine lifespan studies
 could serve as a mechanism to identify favorable or disease-modifying
 variants important to the axis of aging and cancer.
description: All samples were genotyped using the Illumina CanineHD 220k
 BeadChip (Illumina, San Diego, CA, USA). Genotype calls in plink format
 (Bed, bim and fam) are submitted.
description: # GWAS raw genotype files
 [https://doi.org/10.5061/dryad.3j9kd51r2](https://doi.org/10.5061/dryad.3j9kd51r2) A GWAS was performed comparing GR dogs ≥ 14 years to dogs dying prior to age 12 which revealed a significant association to ERBB4, the only member of the epidermal growth factor receptor family capable of serving as both a tumor suppressor gene and an oncogene. No coding variants were identified, however, distinct haplotypes in the 5′UTR were associated with reduced lifespan in two separate populations of GR dogs. Primary ARTICLE https://doi.org/10.1007/s11357-023-00968-2 **Description of the data and file structure** All samples were genotyped using the Illumina CanineHD 220k BeadChip (Illumina, San Diego, CA, USA). Genotype calls in plink format (Bed, bim and fam) are submitted. The files are labeled array1_1214.bed, array1_1214.bim, and array1_1214.fam. ## Sharing/Access information ## Code/Software https://www.cog-genomics.org/plink/ can be used to download PLINK which accepts the file types uploaded here.