2012-11-01
Using genome-wide complex trait analysis to quantify 'missing heritability' in Parkinson's disease
Publication
Publication
Human Molecular Genetics , Volume 21 - Issue 22 p. 4996- 5009
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.
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| doi.org/10.1093/hmg/dds335, hdl.handle.net/1765/55834 | |
| Human Molecular Genetics | |
| Organisation | Erasmus MC: University Medical Center Rotterdam |
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Keller, M., Saad, F., Bras, J., Bettella, F., Nicolaou, N., Simón-Sánchez, J., … McCarthy, M. (2012). Using genome-wide complex trait analysis to quantify 'missing heritability' in Parkinson's disease. Human Molecular Genetics, 21(22), 4996–5009. doi:10.1093/hmg/dds335 |
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