Journal Article

DZNE-2020-02990

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Using genome-wide complex trait analysis to quantify 'missing heritability' in Parkinson's disease.

Keller, M. F. ; Saad, M. ; Bras, J. ; Bettella, F. ; Nicolaou, N. ; Simón-Sánchez, J. ; Mittag, F. ; Büchel, F. ; Sharma, M.DZNE* ; Gibbs, J. R. ; Schulte, C.DZNE* ; Moskvina, V. ; Durr, A. ; Holmans, P. ; Kilarski, L. L. ; Guerreiro, R. ; Hernandez, D. G. ; Brice, A. ; Ylikotila, P. ; Stefánsson, H. ; Majamaa, K. ; Morris, H. R. ; Williams, N. ; Gasser, T.DZNE* ; Heutink, P. ; Wood, N. W. ; Hardy, J. ; Martinez, M. ; Singleton, A. B. ; Nalls, M. A. ; Consortium, I. P. D. G. ; 2, W. T. C. C. C. ; Keller, M. F. ; Nalls, M. A. ; Plagnol, V. ; Sheerin, U.-M. ; Saad, M. ; Simón-Sánchez, J. ; Lesage, S. ; Sveinbjörnsdóttir, S. ; Arepalli, S. ; Ben-Shlomo, Y. ; Berendse, H. W. ; Berg, D. ; Bhatia, K. ; de Bie, R. M. A. ; Biffi, A. ; Bloem, B. ; Bochdanovits, Z. ; Bonin, M. ; Bras, J. ; Brockmann, K. ; Brooks, J. ; Burn, D. J. ; Charlesworth, G. ; Chen, H. ; Chinnery, P. F. ; Chong, S. ; Clarke, C. E. ; Cookson, M. R. ; Cooper, J. M. ; Corvol, J. C. ; Counsell, C. ; Damier, P. ; Dartigues, J.-F. ; Segalen, V. ; Deloukas, P. ; Deuschl, G. ; Dexter, D. T. ; van Dijk, K. D. ; Dillman, A. ; Durif, F. ; Montpied, G. ; Edkins, S. ; Evans, J. R. ; Foltynie, T. ; Gao, J. ; Gardner, M. ; Gibbs, J. R. ; Goate, A. ; Gray, E. ; Guerreiro, R. ; Gústafsson, O. ; Harris, C. ; van Hilten, J. J. ; Hofman, A. ; Hollenbeck, A. ; Holton, J. ; Hu, M. ; Huang, X. ; Huber, H. ; Hudson, G. ; Hunt, S. E. ; Huttenlocher, J. ; Illig, T. ; Jónsson, P. V. ; Lambert, J.-C. ; Langford, C. ; Lees, A. ; Lichtner, P. ; Limousin, P. ; Lopez, G. ; Lorenz, D. ; McNeill, A. ; Moorby, C. ; Moore, M. ; Morris, H. R. ; Morrison, K. E. ; Mudanohwo, E. ; O'Sullivan, S. S. ; Pearson, J. ; Perlmutter, J. S. ; Pétursson, H. ; Pollak, P. ; Post, B. ; Potter, S. ; Ravina, B. ; Revesz, T. ; Riess, O. ; Rivadeneira, F. ; Rizzu, P. ; Ryten, M. ; Sawcer, S. ; Schapira, A. ; Scheffer, H. ; Shaw, K. ; Shoulson, I. ; Sidransky, E. ; Smith, C. ; Spencer, C. C. A. ; Stefánsson, H. ; Steinberg, S. ; Stockton, J. D. ; Strange, A. ; Talbot, K. ; Tanner, C. M. ; Tashakkori-Ghanbaria, A. ; Tison, F. ; Trabzuni, D. ; Traynor, B. J. ; Uitterlinden, A. G. ; Velseboer, D. ; Vidailhet, M. ; Walker, R. ; van de Warrenburg, B. ; Wickremaratchi, M. ; Williams, N. ; Williams-Gray, C. H. ; Winder-Rhodes, S. ; Stefánsson, K. ; Martinez, M. ; Sabatier, P. ; Hardy, J. ; Brice, A. ; Singleton, A. B. ; Wood, N. W. ; Donnelly, P. ; Barroso, I. ; Blackwell, J. M. ; Bramon, E. ; Brown, M. A. ; Casas, J. P. ; Corvin, A. ; Deloukas, P. ; Duncanson, A. ; Jankowski, J. ; Markus, H. S. ; Mathew, C. G. ; Palmer, C. N. A. ; Plomin, R. ; Rautanen, A. ; Sawcer, S. J. ; Trembath, R. C. ; Viswanathan, A. C. ; Wood, N. W. ; Spencer, C. C. A. ; Band, G. ; Bellenguez, C. ; Freeman, C. ; Hellenthal, G. ; Giannoulatou, E. ; Pirinen, M. ; Pearson, R. ; Strange, A. ; Su, Z. ; Vukcevic, D. ; Donnelly, P. ; Langford, C. ; Hunt, S. E. ; Edkins, S. ; Gwilliam, R. ; Blackburn, H. ; Bumpstead, S. J. ; Dronov, S. ; Gillman, M. ; Gray, E. ; Hammond, N. ; Jayakumar, A. ; McCann, O. T. ; Liddle, J. ; Potter, S. C. ; Ravindrarajah, R. ; Ricketts, M. ; Waller, M. ; Weston, P. ; Widaa, S. ; Whittaker, P. ; Barroso, I. ; Deloukas, P.

2012
Oxford Univ. Press Oxford

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Please use a persistent id in citations: doi:10.1093/hmg/dds335

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.

Keyword(s): 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)

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Contributing Institute(s):

1. Microglia and Neuroinflammation (AG Halle)
2. Parkinson Genetics (AG Gasser 1)

Research Program(s):

1. 345 - Population Studies and Genetics (POF3-345) (POF3-345)

Appears in the scientific report 2012

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; PubMed Central ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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