Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Using genome-wide complex trait analysis to quantify 'missing heritability' in Parkinson's disease

Keller, Marguax F., Saad, Mohamad, Bras, Jose, Bettella, Francesco, Nicolaou, Nayia, Simon-Sanchez, Javier, Mittag, Florian, Buchel, Finja, Sharma, Manu, Gibbs, J. Raphael, Schulte, Claudia, Escott-Price, Valentina, Durr, Alexandra, Holmans, Peter Alan, Kilarski, Laura, Guerreiro, Rita, Hernandez, Dena G., Brice, Alexis, Ylikotila, Pauli, Stefansson, Hreinn, Majamaa, Kari, Morris, Huw Rees, Williams, Nigel Melville, Gasser, Thomas, Heutink, Peter, Wood, Nicholas W., Hardy, John, Martinez, Maria, Singleton, Andrew B. and Nalls, Michael A. 2012. Using genome-wide complex trait analysis to quantify 'missing heritability' in Parkinson's disease. Human Molecular Genetics 21 (22) , pp. 4996-5009. 10.1093/hmg/dds335

Full text not available from this repository.

Abstract

Genome-wide association studies (GWASs) have been successful at identifying single-nucleotide polymorphisms (SNPs) highly associated with common traits; however, a great deal of the heritable variation associated with common traits remains unaccounted for within the genome. Genome-wide complex trait analysis (GCTA) is a statistical method that applies a linear mixed model to estimate phenotypic variance of complex traits explained by genome-wide SNPs, including those not associated with the trait in a GWAS. We applied GCTA to 8 cohorts containing 7096 case and 19 455 control individuals of European ancestry in order to examine the missing heritability present in Parkinson's disease (PD). We meta-analyzed our initial results to produce robust heritability estimates for PD types across cohorts. Our results identify 27% (95% CI 17–38, P = 8.08E − 08) phenotypic variance associated with all types of PD, 15% (95% CI −0.2 to 33, P = 0.09) phenotypic variance associated with early-onset PD and 31% (95% CI 17–44, P = 1.34E − 05) phenotypic variance associated with late-onset PD. This is a substantial increase from the genetic variance identified by top GWAS hits alone (between 3 and 5%) and indicates there are substantially more risk loci to be identified. Our results suggest that although GWASs are a useful tool in identifying the most common variants associated with complex disease, a great deal of common variants of small effect remain to be discovered.

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Medicine
Systems Immunity Research Institute (SIURI)
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > R Medicine (General)
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher: Oxford University Press
ISSN: 0964-6906
Last Modified: 11 May 2019 22:31
URI: http://orca-mwe.cf.ac.uk/id/eprint/41921

Citation Data

Cited 94 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item