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000136668 0247_ $$2doi$$a10.1093/hmg/dds335
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000136668 037__ $$aDZNE-2020-02990
000136668 041__ $$aEnglish
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000136668 1001_ $$aKeller, Margaux F$$b0
000136668 245__ $$aUsing genome-wide complex trait analysis to quantify 'missing heritability' in Parkinson's disease.
000136668 260__ $$aOxford$$bOxford Univ. Press$$c2012
000136668 264_1 $$2Crossref$$3online$$bOxford University Press (OUP)$$c2012-08-13
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000136668 520__ $$aGenome-wide association studies (GWASs) have been successful at identifying single-nucleotide polymorphisms (SNPs) highly associated with common traits; however, a great deal of the heritable variation associated with common traits remains unaccounted for within the genome. Genome-wide complex trait analysis (GCTA) is a statistical method that applies a linear mixed model to estimate phenotypic variance of complex traits explained by genome-wide SNPs, including those not associated with the trait in a GWAS. We applied GCTA to 8 cohorts containing 7096 case and 19 455 control individuals of European ancestry in order to examine the missing heritability present in Parkinson's disease (PD). We meta-analyzed our initial results to produce robust heritability estimates for PD types across cohorts. Our results identify 27% (95% CI 17-38, P = 8.08E - 08) phenotypic variance associated with all types of PD, 15% (95% CI -0.2 to 33, P = 0.09) phenotypic variance associated with early-onset PD and 31% (95% CI 17-44, P = 1.34E - 05) phenotypic variance associated with late-onset PD. This is a substantial increase from the genetic variance identified by top GWAS hits alone (between 3 and 5%) and indicates there are substantially more risk loci to be identified. Our results suggest that although GWASs are a useful tool in identifying the most common variants associated with complex disease, a great deal of common variants of small effect remain to be discovered.
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000136668 650_2 $$2MeSH$$aAdult
000136668 650_2 $$2MeSH$$aAged
000136668 650_2 $$2MeSH$$aAged, 80 and over
000136668 650_2 $$2MeSH$$aEuropean Continental Ancestry Group: genetics
000136668 650_2 $$2MeSH$$aFemale
000136668 650_2 $$2MeSH$$aGenetic Predisposition to Disease
000136668 650_2 $$2MeSH$$aGenetic Variation
000136668 650_2 $$2MeSH$$aGenome-Wide Association Study
000136668 650_2 $$2MeSH$$aHumans
000136668 650_2 $$2MeSH$$aMale
000136668 650_2 $$2MeSH$$aMiddle Aged
000136668 650_2 $$2MeSH$$aMultifactorial Inheritance
000136668 650_2 $$2MeSH$$aParkinson Disease: genetics
000136668 650_2 $$2MeSH$$aQuantitative Trait, Heritable
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000136668 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/hmg/ddq469$$o10.1093/hmg/ddq469
000136668 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1146/annurev.genom.9.081307.164242$$o10.1146/annurev.genom.9.081307.164242
000136668 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1002/gepi.20533$$o10.1002/gepi.20533
000136668 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/ng1847$$o10.1038/ng1847
000136668 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1086/519795$$o10.1086/519795
000136668 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1136/bmj.39343.408449.80$$o10.1136/bmj.39343.408449.80
000136668 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1136/bmj.327.7414.557$$o10.1136/bmj.327.7414.557
000136668 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.2307/3001666$$o10.2307/3001666
000136668 999C5 $$2Crossref$$o2011$$y2011