DOI: 10.5061/dryad.np5hqc053
title: PLINK breed data showing SLAMF1 is associated with canine atopic dermatitis

description: Canine atopic dermatitis (CAD) is a common inflammatory skin condition in
 dogs. It is a life-long problem which poses a significant welfare issue
 due to the chronic skin discomfort and pruritus (itch) experienced.
 Excessive scratching, licking and chewing cause self-trauma to the skin
 and increased risk of secondary infections. Several breeds are predisposed
 including the Labrador Retriever, Boxer and French Bulldog, suggesting a
 genetic component to the condition. Our access to a sizeable population of
 dogs genotyped on a medium density single-nucleotide polymorphism (SNP)
 array along with linked clinical record information allows for large-scale
 and highly powered genome-wide association study (GWAS) analysis. In this
 study, over 28 thousand dogs were used to look for genetic changes
 associated with CAD. We identified a statistically significant signal on
 canine chromosome 38, with a particularly strong association in the French
 Bulldog breed. Genome resequencing revealed a provocative splice donor
 variant in SLAMF1 (Signaling lymphocytic activation molecule 1), an immune
 system associated gene. Analysis of further genome sequences and RNA
 samples from the Mars Petcare Biobank confirmed the SLAMF1 variant as a
 strong candidate for causing an increased risk of atopic
 dermatitis.   
description: <strong>Samples</strong> DNA
 samples were collected via commercial testing of Wisdom Panel™ Premium,
 Wisdom Panel™ Essential, Wisdom Panel™ Health and Optimal Selection™
 retail products, and genetic testing performed as a part of Optimal
 Wellness Plans® for puppies, through Banfield Pet Hospital branches
 (Vancouver, WA, USA) and as part of the MARS PETCARE BIOBANK™. Samples
 were either collected through non-invasive cheek swabbing by dog owners or
 veterinary professionals or through blood sampling by a veterinary
 professional at a Banfield Pet Hospital in line with regulations governing
 diagnostic testing. Consent for use of DNA data in research was obtained
 through the client’s agreement with terms and conditions of DNA testing
 through Wisdom Panel. Analysis and sequencing of cDNA were performed using
 samples collected from dogs participating in the Mars Petcare Biobank. All
 samples originated from the United States or Mexico. 
 <strong>Analysis</strong> An
 initial GWAS was performed using 14,378 single breed cases and 14,633
 breed matched controls to tightly control against potential population
 stratification. Within breed GWAS was performed where at least 200 cases
 and controls were available for a given breed. 
 <strong>Inclusion criteria </strong>
 CAD cases and controls were categorized
 based on labelling provided by general veterinary practitioners in the
 Banfield EMR and through criteria set by a board-certified veterinary
 dermatologist. Given the retrospective nature of the data, this is a
 diagnosis of atopic dermatitis in the broad sense which may include dogs
 with food allergic dermatitis.  
 CAD cases were in the age range of 0.3 to 20 years and must have
 received at least three months of ectoparasite control. CAD cases had also
 been diagnosed with recurrent (more than once) clinical signs of atopic
 dermatitis including: Dermatitis, Atopic Allergic; Otitis; Pododermatitis;
 Pruritus; Pyoderma or Malassezia. In addition, CAD cases could also have
 been prescribed recurrent systemic anti-inflammatories, antihistamines or
 medicated ear drops.  Controls
 were in the age range of 3 to 20 years and must not have been diagnosed
 with of any of the following recurrent symptoms: Acne; Alopecia
 Undetermined; Dermatitis (of any variety), Folliculitis; Lichenification;
 Malassezia; Otitis (of any variety); Paronychia; Pododermatitis; Pruritus;
 Pyoderma (of any variety).  Controls also must not have been prescribed
 recurrent systemic or topical anti-inflammatories, antihistamines or
 medicated ear drops.   For
 breed assignment single breed dogs were defined as dogs with greater or
 equal to 80% single breed ancestry as defined by the Wisdom Panel breed
 classification algorithm (BCSYS). 
 <strong>Genotype Analysis </strong>
 Genome-wide association study analysis
 was performed using a linear mixed-model approach in the software package
 GEMMA v0.98.5 including a centered relatedness matrix. PLINK v1.9 was used
 to apply the following quality control: Samples with an overall genotyping
 success rate of lower than 95% across all tested SNPs were also filtered
 out; then, variants below 1% minor allele frequency or lower than 95%
 genotyping success rate were filtered out. 
description: # PLINK breed data showing SLAMF1 is associated with canine atopic
 dermatitis
 [https://doi.org/10.5061/dryad.np5hqc053](https://doi.org/10.5061/dryad.np5hqc053) ## Description of the data and file structure ### Corresponding Author Contact Information ``` Name: Oliver P Forman Institution: Wisdom Panel, Science and Diagnostics, Mars Petcare, US Email: oliver.forman@effem.com ``` ### Dataset Overview This dataset contains the Plink data required to replicate GWAS analysis in "A splice donor variant in *SLAMF1* is associated with canine atopic dermatitis", Oliver P. Forman, et al. ### Description of the data and file structure Each of the datasets contains a set of binary Plink files (.bed, .bim and .bam) annotated with breed abbreviations and case and control numbers. ### Software All available data was produced and can be manipulated with the free software [Plink v1.9](https://www.cog-genomics.org/plink/) Files with the extensions bim and fam are plain text and viewable with any text editor. Files with the extension bed are binary PLINK files viewable with the free python software package, [bed-reader](https://pypi.org/project/bed-reader/), downloadable from pypi. ### Files and variables #### File: atopy\_shiba\_239\_cases\_284\_controls.fam #### File: atopy\_shiba\_239\_cases\_284\_controls.bim #### File: atopy\_shiba\_239\_cases\_284\_controls.bed **Description:** Shiba Inu samples in binary Plink format with 239 cases and 284 breed matched controls #### File: atopy\_husky\_227\_cases\_315\_controls.fam #### File: atopy\_husky\_227\_cases\_315\_controls.bim #### File: atopy\_husky\_227\_cases\_315\_controls.bed **Description:** Husky samples in binary Plink format with 227 cases and 315 breed matched controls #### File: atopy\_greatdane\_215\_cases\_212\_controls.bed #### File: atopy\_greatdane\_215\_cases\_212\_controls.fam #### File: atopy\_greatdane\_215\_cases\_212\_controls.bim **Description:** Great Dane samples in binary Plink format with 215 cases and 212 breed matched controls #### File: atopy\_chihuahua\_304\_cases\_363\_controls.fam #### File: atopy\_chihuahua\_304\_cases\_363\_controls.bim #### File: atopy\_chihuahua\_304\_cases\_363\_controls.bed **Description:** Chihuahua samples in binary Plink format with 304 cases and 363 breed matched controls #### File: atopy\_shih\_tzu\_797\_cases\_929\_controls.fam #### File: atopy\_shih\_tzu\_797\_cases\_929\_controls.bim #### File: atopy\_shih\_tzu\_797\_cases\_929\_controls.bed **Description:** Shih Tzu samples in binary Plink format with 797 cases and 929 breed matched controls #### File: atopy\_yorkie\_663\_cases\_786\_controls.fam #### File: atopy\_yorkie\_663\_cases\_786\_controls.bim #### File: atopy\_yorkie\_663\_cases\_786\_controls.bed **Description:** Yorkshire Terrier samples in binary Plink format with 663 cases and 786 breed matched controls #### File: atopy\_singlebreed\_14378\_cases\_14633\_controls.fam #### File: atopy\_singlebreed\_14378\_cases\_14633\_controls.bim #### File: atopy\_singlebreed\_14378\_cases\_14633\_controls.bed **Description:** Single breed samples in binary Plink format with 14,378 cases and 14,633 breed matched controls #### File: atopy\_min\_schnauzer\_559\_cases\_631\_controls.fam #### File: atopy\_min\_schnauzer\_559\_cases\_631\_controls.bim #### File: atopy\_min\_schnauzer\_559\_cases\_631\_controls.bed **Description:** Miniature Schnauzer samples in binary Plink format with 559 cases and 631 breed matched controls #### File: atopy\_minpoodle\_385\_cases\_464\_controls.fam #### File: atopy\_minpoodle\_385\_cases\_464\_controls.bim #### File: atopy\_minpoodle\_385\_cases\_464\_controls.bed **Description:**  Miniature Poodle samples in binary Plink format with 385 cases and 464 breed matched controls #### File: atopy\_poodle\_461\_cases\_498\_controls.fam #### File: atopy\_poodle\_461\_cases\_498\_controls.bim #### File: atopy\_poodle\_461\_cases\_498\_controls.bed **Description:** Poodle samples in binary Plink format with 461 cases and 498 breed matched controls #### File: atopy\_dachshund\_436\_cases\_507\_controls.fam #### File: atopy\_dachshund\_436\_cases\_507\_controls.bim #### File: atopy\_dachshund\_436\_cases\_507\_controls.bed **Description:** Dachshund samples in binary Plink format with 436 cases and 507 breed matched controls #### File: atopy\_beagle\_349\_cases\_362\_controls.fam #### File: atopy\_beagle\_349\_cases\_362\_controls.bim #### File: atopy\_beagle\_349\_cases\_362\_controls.bed **Description:** Beagle samples in binary Plink format with 349 cases and 362 breed matched controls #### File: atopy\_wpcorgi\_398\_cases\_477\_controls.fam #### File: atopy\_wpcorgi\_398\_cases\_477\_controls.bim #### File: atopy\_wpcorgi\_398\_cases\_477\_controls.bed **Description:** Pembroke Welsh Corgi samples in binary Plink format with 398 cases and 477 breed matched controls #### File: atopy\_golden\_1056\_cases\_1057\_controls.fam #### File: atopy\_golden\_1056\_cases\_1057\_controls.bim #### File: atopy\_golden\_1056\_cases\_1057\_controls.bed **Description:** Golden Retriever samples in binary Plink format with 1,056 cases and 1,057 breed matched controls #### File: atopy\_gsd\_1494\_cases\_1599\_controls.fam #### File: atopy\_gsd\_1494\_cases\_1599\_controls.bim #### File: atopy\_gsd\_1494\_cases\_1599\_controls.bed **Description:** German Shepherd samples in binary Plink format with 1,494 cases and 1,599 breed matched controls #### File: atopy\_lab\_1668\_cases\_1064\_controls.fam #### File: atopy\_lab\_1668\_cases\_1064\_controls.bim #### File: atopy\_lab\_1668\_cases\_1064\_controls.bed **Description:** Labrador samples in binary Plink format with 1,668 cases and 1,064 breed matched controls #### File: atopy\_frenchie\_2138\_cases\_645\_controls.fam #### File: atopy\_frenchie\_2138\_cases\_645\_controls.bim #### File: atopy\_frenchie\_2138\_cases\_645\_controls.bed **Description:** French Bulldog samples in binary Plink format with 2,138 cases and 645 breed matched controls #### File: atopy\_boxer\_447\_cases\_515\_controls.fam #### File: atopy\_boxer\_447\_cases\_515\_controls.bim #### File: atopy\_boxer\_447\_cases\_515\_controls.bed **Description:** Boxer samples in binary Plink format with 447 cases and 515 breed matched controls #### File: atopy\_boston\_478\_cases\_531\_controls.fam #### File: atopy\_boston\_478\_cases\_531\_controls.bim #### File: atopy\_boston\_478\_cases\_531\_controls.bed **Description:** Boston Terrier samples in binary Plink format with 478 cases and 531 controls ## Access information Data was derived from the following sources: * DNA samples collected via commercial testing of Wisdom Panel™ Premium, Wisdom Panel™ Essential, Wisdom Panel™ Health and Optimal Selection™ retail products * Banfield EMR (electronic medical records). For DNA samples collected and submitted by general retail consumers of Wisdom Panel products, data from genotyped dogs was linked with the Banfield EMR by anonymized cross matching of pet and owner information, in accordance with personally identifiable information (PII) regulations.