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

• Published in: PLoS genetics 2015-10, Vol.11 (10), p.e1005593
• Main Authors: Benton, Miles C, Lea, Rodney A, Macartney-Coxson, Donia, Hanna, Michelle, Eccles, David A, Carless, Melanie A, Chambers, Geoffrey K, Bellis, Claire, Goring, Harald H, Curran, Joanne E, Harper, Jacquie L, Gibson, Gregory, Blangero, John, Griffiths, Lyn R
• Format: Article
• Language: English
• Subjects: Binding sites; Cardiovascular disease; Cardiovascular Diseases - genetics; Cardiovascular Diseases - pathology; Chromosomes; Female; Funding; Gene expression; Genetic Pleiotropy; Genetic Predisposition to Disease; Genetics; Genome-Wide Association Study; Genomes; Haplotypes; Humans; Male; Melanesia; Metabolism; Mortality; Phenotype; Polymorphism, Single Nucleotide; Population; Principal Component Analysis; Principal components analysis; Risk factors; Studies
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1005593

Multiphenotype genome-wide association studies (GWAS) may reveal pleiotropic genes, which would remain undetected using single phenotype analyses. Analysis of large pedigrees offers the added advantage of more accurately assessing trait heritability, which can help prioritise genetically influenced phenotypes for GWAS analysis. In this study we performed a principal component analysis (PCA), heritability (h2) estimation and pedigree-based GWAS of 37 cardiovascular disease -related phenotypes in 330 related individuals forming a large pedigree from the Norfolk Island genetic isolate. PCA revealed 13 components explaining >75% of the total variance. Nine components yielded statistically significant h2 values ranging from 0.22 to 0.54 (P