標題: Meta-analysis of Dense Genecentric Association Studies Reveals Common and Uncommon Variants Associated with Height
作者: Lanktree, Matthew B.
Guo, Yiran
Murtaza, Muhammed
Glessner, Joseph T.
Bailey, Swneke D.
Onland-Moret, N. Charlotte
Lettre, Guillaume
Ongen, Halit
Rajagopalan, Ramakrishnan
Johnson, Toby
Shen, Haiqing
Nelson, Christopher P.
Klopp, Norman
Baumert, Jens
Padmanabhan, Sandosh
Pankratz, Nathan
Pankow, James S.
Shah, Sonia
Taylor, Kira
Barnard, John
Peters, Bas J.
Maloney, Cliona M.
Lobmeyer, Maximilian T.
Stanton, Alice
Zafarmand, M. Hadi
Romaine, Simon P. R.
Mehta, Amar
van Iperen, Erik P. A.
Gong, Yan
Price, Tom S.
Smith, Erin N.
Kim, Cecilia E.
Li, Yun R.
Asselbergs, Folkert W.
Atwood, Larry D.
Bailey, Kristian M.
Bhatt, Deepak
Bauer, Florianne
Behr, Elijah R.
Bhangale, Tushar
Boer, Jolanda M. A.
Boehm, Bernhard O.
Bradfield, Jonathan P.
Brown, Morris
Braund, Peter S.
Burton, Paul R.
Carty, Cara
Chandrupatla, Hareesh R.
Chen, Wei
Connell, John
Dalgeorgou, Chrysoula
de Boer, Anthonius
Drenos, Fotios
Elbers, Clara C.
Fang, James C.
Fox, Caroline S.
Frackelton, Edward C.
Fuchs, Barry
Furlong, Clement E.
Gibson, Quince
Gieger, Christian
Goe, Anuj
Grobbee, Diederik E.
Hastie, Claire
Howard, Philip J.
Huang, Guan-Hua
Johnson, W. Craig
Li, Qing
Kleber, Marcus E.
Klein, Barbara E. K.
Klein, Ronald
Kooperberg, Charles
Ky, Bonnie
LaCroix, Andrea
Lanken, Paul
Lathrop, Mark
Li, Mingyao
Marshal, Vanessa
Melander, Olle
Mentch, Frank D.
Meyer, Nuala J.
Monda, Keri L.
Montpetit, Alexandre
Murugesan, Gurunathan
Nakayama, Karen
Nondah, Dave
Onipinla, Abiodun
Rafelt, Suzanne
Newhouse, Stephen J.
Otieno, F. George
Patel, Sanjey R.
Putt, Mary E.
Rodriguez, Santiago
Safa, Radwan N.
Sawyer, Douglas B.
Schreiner, Pamela J.
Simpson, Claire
Sivapalaratnam, Suthesh
Srinivasan, Sathanur R.
Suver, Christine
Swergold, Gary
Sweitzer, Nancy K.
Thomas, Kelly A.
Thorand, Barbara
Timpson, Nicholas J.
Tischfield, Sam
Tobin, Martin
Tomaszweski, Maciej
Verschuren, W. M. Monique
Wallace, Chris
Winkelmann, Bernhard
Zhang, Haitao
Zheng, Dongling
Zhang, Li
Zmuda, Joseph M.
Clarke, Robert
Balmforth, Anthony J.
Danesh, John
Day, Ian N.
Schork, Nicholas J.
de Bakker, Paul I. W.
Delles, Christian
Duggan, David
Hingorani, Aroon D.
Hirschhorn, Joel N.
Hofker, Marten H.
Humphries, Steve E.
Kivimaki, Mika
Lawlor, Debbie A.
Kottke-Marchant, Kandice
Mega, Jessica L.
Mitchell, Braxton D.
Morrow, David A.
Palmen, Jutta
Redline, Susan
Shields, Denis C.
Shuldiner, Alan R.
Sleiman, Patrick M.
Smith, George Davey
Farrall, Martin
Jamshidi, Yalda
Christiani, David C.
Casas, Juan P.
Hall, Alistair S.
Doevendans, Pieter A.
Christie, Jason D.
Berenson, Gerald S.
Murray, Sarah S.
Illig, Thomas
Dorn, Gerald W., II
Cappola, Thomas P.
Boerwinkle, Eric
Sever, Peter
Rader, Daniel J.
Reilly, Muredach P.
Caulfield, Mark
Talmud, Philippa J.
Topol, Eric
Engert, James C.
Wang, Kai
Dominiczak, Anna
Hamsten, Anders
Curtis, Sean P.
Silverstein, Roy L.
Lange, Leslie A.
Sabatine, Marc S.
Trip, Mieke
Saleheen, Danish
Peden, John F.
Cruickshanks, Karen J.
Maerz, Winfried
O'Connell, Jeffrey R.
Klungel, Olaf H.
Wijmenga, Cisca
Maitland-van der Zee, Anke Hilse
Schadt, Eric E.
Johnson, Julie A.
Jarvik, Gail P.
Papanicolaou, George J.
Watkins, Hugh
Grant, Struan F. A.
Munroe, Patricia B.
North, Kari E.
Samani, Nilesh J.
Koenig, Wolfgang
Gaunt, Tom R.
Anand, Sonia S.
van der Schouw, Yvonne T.
Kumari, Meena
Soranzo, Nicole
FitzGerald, Garret A.
Reiner, Alex
Hegele, Robert A.
Hakonarson, Hakon
Keating, Brendan J.
統計學研究所
Institute of Statistics
公開日期: 7-一月-2011
摘要: Height is a classic complex trait with common variants in a growing list of genes known to contribute to the phenotype. Using a genecentric genotyping array targeted toward cardiovascular-related loci, comprising 49,320 SNPs across approximately 2000 loci, we evaluated the association of common and uncommon SNPs with adult height in 114,223 individuals from 47 studies and six ethnicities. A total of 64 loci contained a SNP associated with height at array-wide significance (p < 2.4 x 10(-6)), with 42 loci surpassing the conventional genome-wide significance threshold (p < 5 x 10(-8)). Common variants with minor allele frequencies greater than 5% were observed to be associated with height in 37 previously reported loci. In individuals of European ancestry, uncommon SNPs in IL11 and SMAD3, which would not be genotyped with the use of standard genome-wide genotyping arrays, were strongly associated with height (p < 3 x 10(-11)). Conditional analysis within associated regions revealed five additional variants associated with height independent of lead SNPs within the locus, suggesting allelic heterogeneity. Although underpowered to replicate findings from individuals of European ancestry, the direction of effect of associated variants was largely consistent in African American, South Asian, and Hispanic populations. Overall, we show that dense coverage of genes for uncommon SNPs, coupled with large-scale meta-analysis, can successfully identify additional variants associated with a common complex trait.
URI: http://dx.doi.org/10.1016/j.ajhg.2010.11.007
http://hdl.handle.net/11536/25895
ISSN: 0002-9297
DOI: 10.1016/j.ajhg.2010.11.007
期刊: AMERICAN JOURNAL OF HUMAN GENETICS
Volume: 88
Issue: 1
起始頁: 6
結束頁: 18
顯示於類別:期刊論文


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