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

Miles C. Benton, Rodney A. Lea, Donia Macartney-Coxson, Michelle Hanna, David A. Eccles, Melanie A. Carless, Geoffrey K. Chambers, Claire Bellis, Harald H. Goring, Joanne E. Curran, Jacquie L. Harper, Gregory Gibson, John Blangero, Lyn R. Griffiths

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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-8). These SNPs form a 42kb haplotype block and explain 11% of the genetic variance for this renal function phenotype. Replication analysis of the tagging SNP (rs1396315) in an independent US cohort supports the association (P = 0.000011). Blood transcript analysis showed 35 genes were associated with rs1396315 (P

Original languageEnglish (US)
Article numbere1005593
JournalPLoS Genetics
Volume11
Issue number10
DOIs
StatePublished - 2015
Externally publishedYes

Fingerprint

Melanesia
Genome-Wide Association Study
Pacific Ocean Islands
phenotype
Pedigree
kidneys
pedigree
Phenotype
Kidney
loci
genome
heritability
Principal Component Analysis
Single Nucleotide Polymorphism
principal component analysis
Genetic Pleiotropy
gene
cardiovascular disease
tagging
renal function

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

Benton, M. C., Lea, R. A., Macartney-Coxson, D., Hanna, M., Eccles, D. A., Carless, M. A., ... Griffiths, L. R. (2015). A Phenomic Scan of the Norfolk Island Genetic Isolate Identifies a Major Pleiotropic Effect Locus Associated with Metabolic and Renal Disorder Markers. PLoS Genetics, 11(10), [e1005593]. https://doi.org/10.1371/journal.pgen.1005593

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

In: PLoS Genetics, Vol. 11, No. 10, e1005593, 2015.

Research output: Contribution to journalArticle

Benton, MC, Lea, RA, Macartney-Coxson, D, Hanna, M, Eccles, DA, Carless, MA, Chambers, GK, Bellis, C, Goring, HH, Curran, JE, Harper, JL, Gibson, G, Blangero, J & Griffiths, LR 2015, 'A Phenomic Scan of the Norfolk Island Genetic Isolate Identifies a Major Pleiotropic Effect Locus Associated with Metabolic and Renal Disorder Markers', PLoS Genetics, vol. 11, no. 10, e1005593. https://doi.org/10.1371/journal.pgen.1005593
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. / A Phenomic Scan of the Norfolk Island Genetic Isolate Identifies a Major Pleiotropic Effect Locus Associated with Metabolic and Renal Disorder Markers. In: PLoS Genetics. 2015 ; Vol. 11, No. 10.
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