Journal
NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-07692-y
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Funding
- High Value Nutrition National Science (MBIE/HVN) [3710040]
- Royal Society of New Zealand Marsden Fund [16-UOO-072]
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Clinical studies of non-communicable diseases identify multimorbidities that suggest a common set of predisposing factors. Despite the fact that humans have similar to 24,000 genes, we do not understand the genetic pathways that contribute to the development of multimorbid non-communicable disease. Here we create a multimorbidity atlas of traits based on pleiotropy of spatially regulated genes. Using chromatin interaction and expression Quantitative Trait Loci (eQTL) data, we analyse 20,782 variants (p < 5 x 10(-6)) associated with 1351 phenotypes to identify 16,248 putative spatial eQTL-eGene pairs that are involved in 76,013 short- and long-range regulatory interactions (FDR < 0.05) in different human tissues. Convex biclustering of spatial eGenes that are shared among phenotypes identifies complex interrelationships between nominally different phenotype-associated SNPs. Our approach enables the simultaneous elucidation of variant interactions with target genes that are drivers of multimorbidity, and those that contribute to unique phenotype associated characteristics.
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