Meta-analysis of gene-level associations for rare variants based on single-variant statistics.

Détails

ID Serval
serval:BIB_69B6E960E2D0
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Meta-analysis of gene-level associations for rare variants based on single-variant statistics.
Périodique
American Journal of Human Genetics
Auteur⸱e⸱s
Hu Y.J., Berndt S.I., Gustafsson S., Ganna A., Hirschhorn J., Hirschhorn J., North K.E., Ingelsson E., Lin D.Y.
Collaborateur⸱rice⸱s
Genetic Investigation of ANthropometric Traits (GIANT) Consortium
Contributeur⸱rice⸱s
Berndt S.I., Gustafsson S., Mägi R., Ganna A., Wheeler E., Feitosa M.F., Justice A.E., Monda K.L., Croteau-Chonka D.C., Day F.R., Esko T., Fall T., Ferreira T., Gentilini D., Jackson A.U., Luan J., Randall J.C., Vedantam S., Willer C.J., Winkler T.W., Wood A.R., Workalemahu T., Hu Y.J., Lee S.H., Liang L., Lin D.Y., Min J.L., Neale B.M., Thorleifsson G., Yang J., Albrecht E., Amin N., Bragg-Gresham J.L., Cadby G., den Heijer M., Eklund N., Fischer K., Goel A., Hottenga J.J., Huffman J.E., Jarick I., Johansson Å., Johnson T., Kanoni S., Kleber M.E., König I.R., Kristiansson K., Kutalik Z., Lamina C., Lecoeur C., Li G., Mangino M., McArdle W.L., Medina-Gomez C., Müller-Nurasyid M., Ngwa J.S., Nolte I.M., Paternoster L., Pechlivanis S., Perola M., Peters M.J., Preuss M., Rose L.M., Shi J., Shungin D., Smith A.V., Strawbridge R.J., Surakka I., Teumer A., Trip M.D., Tyrer J., Van Vliet-Ostaptchouk J.V., Vandenput L., Waite L.L., Zhao J.H., Absher D., Asselbergs F.W., Atalay M., Attwood A.P., Balmforth A.J., Basart H., Beilby J., Bonnycastle L.L., Brambilla P., Bruinenberg M., Campbell H., Chasman D.I., Chines P.S., Collins F.S., Connell J.M., Cookson W., de Faire U., de Vegt F., Dei M., Dimitriou M., Edkins S., Estrada K., Evans D.M., Farrall M., Ferrario M.M., Ferrières J., Franke L., Frau F., Gejman P.V., Grallert H., Grönberg H., Gudnason V., Hall A.S., Hall P., Hartikainen A.L., Hayward C., Heard-Costa N.L., Heath A.C., Hebebrand J., Homuth G., Hu F.B., Hunt S.E., Hyppönen E., Iribarren C., Jacobs K.B., Jansson J.O., Jula A., Kähönen M., Kathiresan S., Kee F., Khaw K.T., Kivimaki M., Koenig W., Kraja A.T., Kumari M., Kuulasmaa K., Kuusisto J., Laitinen J.H., Lakka T.A., Langenberg C., Launer L.J., Lind L., Lindström J., Liu J., Liuzzi A., Lokki M.L., Lorentzon M., Madden P.A., Magnusson P.K., Manunta P., Marek D., März W., Mateo Leach I., McKnight B., Medland S.E., Mihailov E., Milani L., Montgomery G.W., Mooser V., Mühleisen T.W., Munroe P.B., Musk A.W., Narisu N., Navis G., Nicholson G., Nohr E.A., Ong K.K., Oostra B.A., Palmer C.N., Palotie A., Peden J.F., Pedersen N., Peters A., Polasek O., Pouta A., Pramstaller P.P., Prokopenko I., Pütter C., Radhakrishnan A., Raitakari O., Rendon A., Rivadeneira F., Rudan I., Saaristo T.E., Sambrook J.G., Sanders A.R., Sanna S., Saramies J., Schipf S., Schreiber S., Schunkert H., Shin S.Y., Signorini S., Sinisalo J., Skrobek B., Soranzo N., Stančáková A., Stark K., Stephens J.C., Stirrups K., Stolk R.P., Stumvoll M., Swift A.J., Theodoraki E.V., Thorand B., Tregouet D.A., Tremoli E., Van der Klauw M.M., van Meurs J.B., Vermeulen S.H., Viikari J., Virtamo J., Vitart V., Waeber G., Wang Z., Widén E., Wild SH., Willemsen G., Winkelmann B.R., Witteman J.C., Wolffenbuttel B.H., Wong A., Wright A.F., Zillikens M.C., Amouyel P., Boehm B.O., Boerwinkle E., Boomsma D.I., Caulfield M.J., Chanock S.J., Cupples L.A., Cusi D., Dedoussis G.V., Erdmann J., Eriksson J.G., Franks P.W., Froguel P., Gieger C., Gyllensten U., Hamsten A., Harris T.B., Hengstenberg C., Hicks A.A., Hingorani A., Hinney A., Hofman A., Hovingh K.G., Hveem K., Illig T., Jarvelin M.R., Jöckel K.H., Keinanen-Kiukaanniemi S.M., Kiemeney L.A., Kuh D., Laakso M., Lehtimäki T., Levinson D.F., Martin N.G., Metspalu A., Morris A.D., Nieminen M.S., Njølstad I., Ohlsson C., Oldehinkel A.J., Ouwehand W.H., Palmer L.J., Penninx B., Power C., Province M.A., Psaty B.M., Qi L., Rauramaa R., Ridker P.M., Ripatti S., Salomaa V., Samani N.J., Snieder H., Sørensen T.I., Spector T.D., Stefansson K., Tönjes A., Tuomilehto J., Uitterlinden A.G., Uusitupa M., van der Harst P., Vollenweider P., Wallaschofski H., Wareham N.J., Watkins H., Wichmann H.E., Wilson J.F., Abecasis G.R., Assimes T.L., Barroso I., Boehnke M., Borecki I.B., Deloukas P., Fox C.S., Frayling T., Groop L.C., Haritunian T., Heid I.M., Hunter D., Kaplan R.C., Karpe F., Moffatt M., Mohlke K.L., O'Connell J.R., Pawitan Y., Schadt E.E., Schlessinger D., Steinthorsdottir V., Strachan D.P., Thorsteinsdottir U., van Duijn C.M., Visscher P.M., Di Blasio A.M., Hirschhorn J.N., Lindgren C.M., Morris A.P., Meyre D., Scherag A., McCarthy M.I., Speliotes E.K., North K.E., Loos R.J., Ingelsson E.
ISSN
1537-6605 (Electronic)
ISSN-L
0002-9297
Statut éditorial
Publié
Date de publication
07/2013
Volume
93
Numéro
2
Pages
236-248
Langue
anglais
Notes
Publication types: Journal Article ; Meta-Analysis ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural Publication Status: ppublish
Résumé
Meta-analysis of genome-wide association studies (GWASs) has led to the discoveries of many common variants associated with complex human diseases. There is a growing recognition that identifying "causal" rare variants also requires large-scale meta-analysis. The fact that association tests with rare variants are performed at the gene level rather than at the variant level poses unprecedented challenges in the meta-analysis. First, different studies may adopt different gene-level tests, so the results are not compatible. Second, gene-level tests require multivariate statistics (i.e., components of the test statistic and their covariance matrix), which are difficult to obtain. To overcome these challenges, we propose to perform gene-level tests for rare variants by combining the results of single-variant analysis (i.e., p values of association tests and effect estimates) from participating studies. This simple strategy is possible because of an insight that multivariate statistics can be recovered from single-variant statistics, together with the correlation matrix of the single-variant test statistics, which can be estimated from one of the participating studies or from a publicly available database. We show both theoretically and numerically that the proposed meta-analysis approach provides accurate control of the type I error and is as powerful as joint analysis of individual participant data. This approach accommodates any disease phenotype and any study design and produces all commonly used gene-level tests. An application to the GWAS summary results of the Genetic Investigation of ANthropometric Traits (GIANT) consortium reveals rare and low-frequency variants associated with human height. The relevant software is freely available.
Mots-clé
Computer Simulation, Gene Frequency, Genetic Variation, Genome-Wide Association Study, Genotype, Humans, Models, Genetic, Phenotype, Polymorphism, Single Nucleotide, Receptors, LDL/genetics, Receptors, Odorant/genetics, Software
Pubmed
Web of science
Open Access
Oui
Création de la notice
13/08/2013 11:26
Dernière modification de la notice
20/08/2019 15:24
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