Gita A Pathak1, Zhengyang Zhou2, Talisa K Silzer1, Robert C Barber3, Nicole R Phillips1. 1. Department of Microbiology, Immunology and Genetics, Graduate School of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, Texas, USA. 2. Department of Biostatistics and Epidemiology, School of Public Health, University of North Texas Health Science Center, Fort Worth, Texas, USA. 3. Department of Pharmacology & Neuroscience, Graduate School of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, Texas, USA.
Abstract
INTRODUCTION: We compared genetic variants between Alzheimer's disease (AD) and two age-related cancers-breast and prostate -to identify single-nucleotide polymorphisms (SNPs) that are associated with inverse comorbidity of AD and cancer. METHODS: Bayesian multinomial regression was used to compare sex-stratified cases (AD and cancer) against controls in a two-stage study. A ±500 KB region around each replicated hit was imputed and analyzed after merging individuals from the two stages. The microRNAs (miRNAs) that target the genes involving these SNPs were analyzed for miRNA family enrichment. RESULTS: We identified 137 variants with inverse odds ratios for AD and cancer located on chromosomes 19, 4, and 5. The mapped miRNAs within the network were enriched for miR-17 and miR-515 families. DISCUSSION: The identified SNPs were rs4298154 (intergenic), within TOMM40/APOE/APOC1, MARK4, CLPTM1, and near the VDAC1/FSTL4 locus. The miRNAs identified in our network have been previously reported to have inverse expression in AD and cancer.
INTRODUCTION: We compared genetic variants between Alzheimer's disease (AD) and two age-related cancers-breast and prostate -to identify single-nucleotide polymorphisms (SNPs) that are associated with inverse comorbidity of AD and cancer. METHODS: Bayesian multinomial regression was used to compare sex-stratified cases (AD and cancer) against controls in a two-stage study. A ±500 KB region around each replicated hit was imputed and analyzed after merging individuals from the two stages. The microRNAs (miRNAs) that target the genes involving these SNPs were analyzed for miRNA family enrichment. RESULTS: We identified 137 variants with inverse odds ratios for AD and cancer located on chromosomes 19, 4, and 5. The mapped miRNAs within the network were enriched for miR-17 and miR-515 families. DISCUSSION: The identified SNPs were rs4298154 (intergenic), within TOMM40/APOE/APOC1, MARK4, CLPTM1, and near the VDAC1/FSTL4 locus. The miRNAs identified in our network have been previously reported to have inverse expression in AD and cancer.
Authors: Michele Salemi; Maria Paola Mogavero; Giuseppe Lanza; Laura M Mongioì; Aldo E Calogero; Raffaele Ferri Journal: Cells Date: 2022-06-15 Impact factor: 7.666
Authors: Monica Ospina-Romero; M Maria Glymour; Eleanor Hayes-Larson; Elizabeth Rose Mayeda; Rebecca E Graff; Willa D Brenowitz; Sarah F Ackley; John S Witte; Lindsay C Kobayashi Journal: JAMA Netw Open Date: 2020-11-02