title: Phenome-Wide Association Study to Explore Relationships between Immune System Related Genetic Loci and Complex Traits and Diseases.
abstract: We performed a Phenome-Wide Association Study (PheWAS) to identify interrelationships between the immune system genetic architecture and a wide array of phenotypes from two de-identified electronic health record (EHR) biorepositories. We selected variants within genes encoding critical factors in the immune system and variants with known associations with autoimmunity. To define case/control status for EHR diagnoses, we used International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes from 3,024 Geisinger Clinic MyCode® subjects (470 diagnoses) and 2,899 Vanderbilt University Medical Center BioVU biorepository subjects (380 diagnoses). A pooled-analysis was also carried out for the replicating results of the two data sets. We identified new associations with potential biological relevance including SNPs in tumor necrosis factor (TNF) and ankyrin-related genes associated with acute and chronic sinusitis and acute respiratory tract infection. The two most significant associations identified were for the C6orf10 SNP rs6910071 and "rheumatoid arthritis" (ICD-9 code category 714) (pMETAL = 2.58 x 10-9) and the ATN1 SNP rs2239167 and "diabetes mellitus, type 2" (ICD-9 code category 250) (pMETAL = 6.39 x 10-9). This study highlights the utility of using PheWAS in conjunction with EHRs to discover new genotypic-phenotypic associations for immune-system related genetic loci.
authors: Biomedical and Translational Informatics Program, Geisinger Health System, Danville, Pennsylvania, United States of America.|Center for Systems Genomics, Department of Biochemistry and Molecular Biology, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, Pennsylvania, United States of America.
authors: Anurag
authors: A
authors: Verma
authors: Center for Systems Genomics, Department of Biochemistry and Molecular Biology, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, Pennsylvania, United States of America.
authors: Anna O
authors: AO
authors: Basile
authors: Biomedical and Translational Informatics Program, Geisinger Health System, Danville, Pennsylvania, United States of America.
authors: Yuki
authors: Y
authors: Bradford
authors: The Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, Pennsylvania, United States of America.|Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa.
authors: Helena
authors: H
authors: Kuivaniemi
authors: The Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, Pennsylvania, United States of America.|Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa.
authors: Gerard
authors: G
authors: Tromp
authors: The Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, Pennsylvania, United States of America.
authors: David
authors: D
authors: Carey
authors: Department of Medical Genetics and Molecular Biochemistry, Temple University School of Medicine, Philadelphia, Pennsylvania, United States of America.
authors: Glenn S
authors: GS
authors: Gerhard
authors: The Vanderbilt Vaccine Center, Vanderbilt University, Nashville Tennessee, United States of America.
authors: James E
authors: JE
authors: Crowe
authors: Biomedical and Translational Informatics Program, Geisinger Health System, Danville, Pennsylvania, United States of America.|Center for Systems Genomics, Department of Biochemistry and Molecular Biology, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, Pennsylvania, United States of America.
authors: Marylyn D
authors: MD
authors: Ritchie
authors: Biomedical and Translational Informatics Program, Geisinger Health System, Danville, Pennsylvania, United States of America.
authors: Sarah A
authors: SA
authors: Pendergrass
mesh_terms: D017487:Ankyrins / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000473:pathology; D057286:Electronic Health Records; D056726:Genetic Association Studies; D056426:Genetic Loci; D005838:Genotype; D006801:Humans; D007107:Immune System / Q000378:metabolism*; D015810:Linkage Disequilibrium; D009419:Nerve Tissue Proteins / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012141:Respiratory Tract Infections / Q000235:genetics / Q000473:pathology; D012852:Sinusitis / Q000235:genetics / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D017487:Ankyrins; D009419:Nerve Tissue Proteins; D014409:Tumor Necrosis Factor-alpha; C095278:atrophin-1