A Phenomic Scan of the Norfolk Island Genetic Isolate Identifies a Major Pleiotropic Effect Locus Associated with Metabolic and Renal Disorder Markers

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While many large genetic association studies have identified genes playing a role in complex disorders, there is still concern over the amount of missing genetic heritability. With this in mind, we have used a data reduction approach alongside pedigree-based association to obtain highly heritable components which explain 'hidden' variance of multiphenotypes within a large pedigree from the Norfolk Island genetic isolate. The most heritable of these components involved 7 traits reflecting metabolic and renal functionality, association of which locates to an intergenic region on chromosome 1p22.2. By integrating gene expression information, we identified enrichment of a purine metabolism pathway, further strengthening the metabolic nature of the observed association. Adding additional support to our approach, we show association of the tagging SNP (rs1396315) in an independent US population. The findings presented here are of particular interest as they implicate pleiotropic effect loci and newly associated biological pathways underlying cardiovascular disease risk.

Vyšlo v časopise: A Phenomic Scan of the Norfolk Island Genetic Isolate Identifies a Major Pleiotropic Effect Locus Associated with Metabolic and Renal Disorder Markers. PLoS Genet 11(10): e32767. doi:10.1371/journal.pgen.1005593
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005593

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