136668 20240321220120.0 10.1093/hmg/dds335 doi pmid:22892372 pmid pmc:PMC3576713 pmc 0964-6906 ISSN 1460-2083 ISSN altmetric:888715 altmetric DZNE-2020-02990 English 570 Keller, Margaux F 0 Using genome-wide complex trait analysis to quantify 'missing heritability' in Parkinson's disease. Oxford 2012 Oxford Univ. Press online Crossref Oxford University Press (OUP) 2012-08-13 print Crossref Oxford University Press (OUP) 2012-11-15 article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1593691364_9583 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote 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. 345 - Population Studies and Genetics (POF3-345) G:(DE-HGF)POF3-345 POF3-345 POF III 0 Dataset connected to CrossRef, PubMed, Adult MeSH Aged MeSH Aged, 80 and over MeSH European Continental Ancestry Group: genetics MeSH Female MeSH Genetic Predisposition to Disease MeSH Genetic Variation MeSH Genome-Wide Association Study MeSH Humans MeSH Male MeSH Middle Aged MeSH Multifactorial Inheritance MeSH Parkinson Disease: genetics MeSH Quantitative Trait, Heritable MeSH Saad, Mohamad 1 Bras, Jose 2 Bettella, Francesco 3 Nicolaou, Nayia 4 Simón-Sánchez, Javier 5 Mittag, Florian 6 Büchel, Finja 7 Sharma, Manu P:(DE-2719)9000296 8 Gibbs, J Raphael 9 Schulte, Claudia P:(DE-2719)9000366 10 Moskvina, Valentina 11 Durr, Alexandra P:(DE-HGF)0 12 Holmans, Peter 13 Kilarski, Laura L 14 Guerreiro, Rita 15 Hernandez, Dena G P:(DE-HGF)0 16 Brice, Alexis 17 Ylikotila, Pauli 18 Stefánsson, Hreinn 19 Majamaa, Kari 20 Morris, Huw R 21 Williams, Nigel 22 Gasser, Thomas P:(DE-2719)2320009 23 Heutink, Peter P:(DE-HGF)0 24 Wood, Nicholas W 25 Hardy, John 26 Martinez, Maria 27 Singleton, Andrew B 28 Nalls, Michael A 29 Consortium, International Parkinson's Disease Genomics 30 2, Wellcome Trust Case Control Consortium 31 Keller, Margaux F 32 Nalls, Michael A 33 Plagnol, Vincent 34 Sheerin, Una-Marie 35 Saad, Mohamad 36 Simón-Sánchez, Javier 37 Lesage, Suzanne 38 Sveinbjörnsdóttir, Sigurlaug 39 Arepalli, Sampath 40 Ben-Shlomo, Yoav 41 Berendse, Henk W 42 Berg, Daniela P:(DE-HGF)0 43 Bhatia, Kailash 44 de Bie, Rob M A 45 Biffi, Alessandro 46 Bloem, Bas 47 Bochdanovits, Zoltan 48 Bonin, Michael 49 Bras, Jose 50 Brockmann, Kathrin P:(DE-HGF)0 51 Brooks, Janet 52 Burn, David J 53 Charlesworth, Gavin 54 Chen, Honglei 55 Chinnery, Patrick F 56 Chong, Sean 57 Clarke, Carl E 58 Cookson, Mark R 59 Cooper, J Mark 60 Corvol, Jean Christophe 61 Counsell, Carl 62 Damier, Philippe 63 Dartigues, Jean-François 64 Segalen, Victor 65 Deloukas, Panos 66 Deuschl, Günther P:(DE-HGF)0 67 Dexter, David T 68 van Dijk, Karin D 69 Dillman, Allissa 70 Durif, Frank 71 Montpied, Gabriel 72 Edkins, Sarah 73 Evans, Jonathan R 74 Foltynie, Thomas 75 Gao, Jianjun 76 Gardner, Michelle 77 Gibbs, J Raphael 78 Goate, Alison 79 Gray, Emma 80 Guerreiro, Rita 81 Gústafsson, Omar 82 Harris, Clare 83 van Hilten, Jacobus J 84 Hofman, Albert 85 Hollenbeck, Albert 86 Holton, Janice 87 Hu, Michele 88 Huang, Xuemei 89 Huber, Heiko P:(DE-HGF)0 90 Hudson, Gavin 91 Hunt, Sarah E 92 Huttenlocher, Johanna P:(DE-HGF)0 93 Illig, Thomas 94 Jónsson, Pálmi V 95 Lambert, Jean-Charles 96 Langford, Cordelia 97 Lees, Andrew 98 Lichtner, Peter 99 Limousin, Patricia 100 Lopez, Grisel 101 Lorenz, Delia 102 McNeill, Alisdair 103 Moorby, Catriona 104 Moore, Matthew 105 Morris, Huw R 106 Morrison, Karen E 107 Mudanohwo, Ese 108 O'Sullivan, Sean S 109 Pearson, Justin 110 Perlmutter, Joel S 111 Pétursson, Hjörvar 112 Pollak, Pierre 113 Post, Bart 114 Potter, Simon 115 Ravina, Bernard 116 Revesz, Tamas 117 Riess, Olaf 118 Rivadeneira, Fernando 119 Rizzu, Patrizia P:(DE-HGF)0 120 Ryten, Mina 121 Sawcer, Stephen 122 Schapira, Anthony 123 Scheffer, Hans 124 Shaw, Karen 125 Shoulson, Ira 126 Sidransky, Ellen 127 Smith, Colin 128 Spencer, Chris C A 129 Stefánsson, Hreinn 130 Steinberg, Stacy 131 Stockton, Joanna D 132 Strange, Amy 133 Talbot, Kevin 134 Tanner, Carlie M 135 Tashakkori-Ghanbaria, Avazeh 136 Tison, François 137 Trabzuni, Daniah 138 Traynor, Bryan J 139 Uitterlinden, André G 140 Velseboer, Daan 141 Vidailhet, Marie 142 Walker, Robert 143 van de Warrenburg, Bart 144 Wickremaratchi, Mirdhu 145 Williams, Nigel 146 Williams-Gray, Caroline H 147 Winder-Rhodes, Sophie 148 Stefánsson, Kári 149 Martinez, Maria 150 Sabatier, Paul 151 Hardy, John 152 Brice, Alexis 153 Singleton, Andrew B 154 Wood, Nicholas W 155 Donnelly, Peter 156 Barroso, Ines 157 Blackwell, Jenefer M 158 Bramon, Elvira 159 Brown, Matthew A 160 Casas, Juan P 161 Corvin, Aiden 162 Deloukas, Panos 163 Duncanson, Audrey 164 Jankowski, Janusz 165 Markus, Hugh S 166 Mathew, Christopher G 167 Palmer, Colin N A 168 Plomin, Robert 169 Rautanen, Anna 170 Sawcer, Stephen J 171 Trembath, Richard C 172 Viswanathan, Ananth C 173 Wood, Nicholas W 174 Spencer, Chris C A 175 Band, Gavin 176 Bellenguez, Céline 177 Freeman, Colin 178 Hellenthal, Garrett 179 Giannoulatou, Eleni 180 Pirinen, Matti 181 Pearson, Richard 182 Strange, Amy 183 Su, Zhan 184 Vukcevic, Damjan 185 Donnelly, Peter 186 Langford, Cordelia 187 Hunt, Sarah E 188 Edkins, Sarah 189 Gwilliam, Rhian 190 Blackburn, Hannah 191 Bumpstead, Suzannah J 192 Dronov, Serge 193 Gillman, Matthew 194 Gray, Emma 195 Hammond, Naomi 196 Jayakumar, Alagurevathi 197 McCann, Owen T 198 Liddle, Jennifer 199 Potter, Simon C 200 Ravindrarajah, Radhi 201 Ricketts, Michelle 202 Waller, Matthew 203 Weston, Paul 204 Widaa, Sara 205 Whittaker, Pamela 206 Barroso, Ines 207 Deloukas, Panos 208 10.1093/hmg/dds335 : Oxford University Press (OUP), 2012-08-13 22 4996-5009 journal-article Crossref Human Molecular Genetics 21 2012 0964-6906 10.1093/hmg/dds335 Vol. 21, no. 22, p. 4996 - 5009 PERI:(DE-600)1474816-2 22 21:22<4996 - 5009 4996-5009 Human molecular genetics 21 2012 0964-6906 Pubmed Central http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3576713 oai:pub.dzne.de:136668 VDB Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 8 P:(DE-2719)9000296 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 10 P:(DE-2719)9000366 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 23 P:(DE-2719)2320009 DE-HGF Forschungsbereich Gesundheit Erkrankungen des Nervensystems G:(DE-HGF)POF3-340 G:(DE-HGF)POF3-345 G:(DE-HGF)POF3-300 Population Studies and Genetics 0 2012 Nationallizenz StatID:(DE-HGF)0420 StatID DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS DBCoverage StatID:(DE-HGF)0300 StatID Medline DBCoverage StatID:(DE-HGF)0310 StatID NCBI Molecular Biology Database DBCoverage StatID:(DE-HGF)0320 StatID PubMed Central JCR StatID:(DE-HGF)0100 StatID HUM MOL GENET : 2017 DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List WoS StatID:(DE-HGF)0110 StatID Science Citation Index DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection WoS StatID:(DE-HGF)0111 StatID Science Citation Index Expanded DBCoverage StatID:(DE-HGF)1030 StatID Current Contents - Life Sciences DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews IF < 5 StatID:(DE-HGF)9900 StatID I:(DE-2719)1013034 AG Halle Microglia and Neuroinflammation 0 I:(DE-2719)1210000 AG Gasser 1 Parkinson Genetics 1 journal VDB I:(DE-2719)1013034 I:(DE-2719)1210000 UNRESTRICTED 10.1038/ng.608 -- missing cx lookup -- Crossref 10.1038/ng.608 10.1038/ng.823 -- missing cx lookup -- Crossref 10.1038/ng.823 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