17 Keller, Margaux F Saad, Mohamad Bras, Jose Bettella, Francesco Nicolaou, Nayia Simón-Sánchez, Javier Mittag, Florian Büchel, Finja Sharma, Manu Gibbs, J Raphael Schulte, Claudia Moskvina, Valentina Durr, Alexandra Holmans, Peter Kilarski, Laura L Guerreiro, Rita Hernandez, Dena G Brice, Alexis Ylikotila, Pauli Stefánsson, Hreinn Majamaa, Kari Morris, Huw R Williams, Nigel Gasser, Thomas Heutink, Peter Wood, Nicholas W Hardy, John Martinez, Maria Singleton, Andrew B Nalls, Michael A Consortium, International Parkinson's Disease Genomics 2, Wellcome Trust Case Control Consortium Keller, Margaux F Nalls, Michael A Plagnol, Vincent Sheerin, Una-Marie Saad, Mohamad Simón-Sánchez, Javier Lesage, Suzanne Sveinbjörnsdóttir, Sigurlaug Arepalli, Sampath Ben-Shlomo, Yoav Berendse, Henk W Berg, Daniela Bhatia, Kailash de Bie, Rob M A Biffi, Alessandro Bloem, Bas Bochdanovits, Zoltan Bonin, Michael Bras, Jose Brockmann, Kathrin Brooks, Janet Burn, David J Charlesworth, Gavin Chen, Honglei Chinnery, Patrick F Chong, Sean Clarke, Carl E Cookson, Mark R Cooper, J Mark Corvol, Jean Christophe Counsell, Carl Damier, Philippe Dartigues, Jean-François Segalen, Victor Deloukas, Panos Deuschl, Günther Dexter, David T van Dijk, Karin D Dillman, Allissa Durif, Frank Montpied, Gabriel Edkins, Sarah Evans, Jonathan R Foltynie, Thomas Gao, Jianjun Gardner, Michelle Gibbs, J Raphael Goate, Alison Gray, Emma Guerreiro, Rita Gústafsson, Omar Harris, Clare van Hilten, Jacobus J Hofman, Albert Hollenbeck, Albert Holton, Janice Hu, Michele Huang, Xuemei Huber, Heiko Hudson, Gavin Hunt, Sarah E Huttenlocher, Johanna Illig, Thomas Jónsson, Pálmi V Lambert, Jean-Charles Langford, Cordelia Lees, Andrew Lichtner, Peter Limousin, Patricia Lopez, Grisel Lorenz, Delia McNeill, Alisdair Moorby, Catriona Moore, Matthew Morris, Huw R Morrison, Karen E Mudanohwo, Ese O'Sullivan, Sean S Pearson, Justin Perlmutter, Joel S Pétursson, Hjörvar Pollak, Pierre Post, Bart Potter, Simon Ravina, Bernard Revesz, Tamas Riess, Olaf Rivadeneira, Fernando Rizzu, Patrizia Ryten, Mina Sawcer, Stephen Schapira, Anthony Scheffer, Hans Shaw, Karen Shoulson, Ira Sidransky, Ellen Smith, Colin Spencer, Chris C A Stefánsson, Hreinn Steinberg, Stacy Stockton, Joanna D Strange, Amy Talbot, Kevin Tanner, Carlie M Tashakkori-Ghanbaria, Avazeh Tison, François Trabzuni, Daniah Traynor, Bryan J Uitterlinden, André G Velseboer, Daan Vidailhet, Marie Walker, Robert van de Warrenburg, Bart Wickremaratchi, Mirdhu Williams, Nigel Williams-Gray, Caroline H Winder-Rhodes, Sophie Stefánsson, Kári Martinez, Maria Sabatier, Paul Hardy, John Brice, Alexis Singleton, Andrew B Wood, Nicholas W Donnelly, Peter Barroso, Ines Blackwell, Jenefer M Bramon, Elvira Brown, Matthew A Casas, Juan P Corvin, Aiden Deloukas, Panos Duncanson, Audrey Jankowski, Janusz Markus, Hugh S Mathew, Christopher G Palmer, Colin N A Plomin, Robert Rautanen, Anna Sawcer, Stephen J Trembath, Richard C Viswanathan, Ananth C Wood, Nicholas W Spencer, Chris C A Band, Gavin Bellenguez, Céline Freeman, Colin Hellenthal, Garrett Giannoulatou, Eleni Pirinen, Matti Pearson, Richard Strange, Amy Su, Zhan Vukcevic, Damjan Donnelly, Peter Langford, Cordelia Hunt, Sarah E Edkins, Sarah Gwilliam, Rhian Blackburn, Hannah Bumpstead, Suzannah J Dronov, Serge Gillman, Matthew Gray, Emma Hammond, Naomi Jayakumar, Alagurevathi McCann, Owen T Liddle, Jennifer Potter, Simon C Ravindrarajah, Radhi Ricketts, Michelle Waller, Matthew Weston, Paul Widaa, Sara Whittaker, Pamela Barroso, Ines Deloukas, Panos AG Halle AG Gasser 1 Human molecular genetics Human molecular genetics Oxford Univ. Press Oxford 0964-6906 10.1093/hmg/dds335 English 4996-5009 22 21 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. PUB:(DE-HGF)16, ; 0, ; Adult Aged Aged, 80 and over European Continental Ancestry Group: genetics Female Genetic Predisposition to Disease Genetic Variation Genome-Wide Association Study Humans Male Middle Aged Multifactorial Inheritance Parkinson Disease: genetics Quantitative Trait, Heritable Journal Article 2012 DZNE-2020-02990 2012 pmc:PMC3576713 pmid:22892372 https://pub.dzne.de/record/136668 https://doi.org/10.1093/hmg/dds335