Abstract
Original language | English |
---|---|
Pages (from-to) | 6-18 |
Journal | American journal of human genetics |
Volume | 88 |
Issue number | 1 |
DOIs | |
Publication status | Published - 2011 |
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In: American journal of human genetics, Vol. 88, No. 1, 2011, p. 6-18.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Meta-analysis of Dense Genecentric Association Studies Reveals Common and Uncommon Variants Associated with Height
AU - Lanktree, Matthew B.
AU - Guo, Yiran
AU - Murtaza, Muhammed
AU - Glessner, Joseph T.
AU - Bailey, Swneke D.
AU - Onland-Moret, N. Charlotte
AU - Lettre, Guillaume
AU - Ongen, Halit
AU - Rajagopalan, Ramakrishnan
AU - Johnson, Toby
AU - Shen, Haiqing
AU - Nelson, Christopher P.
AU - Klopp, Norman
AU - Baumert, Jens
AU - Padmanabhan, Sandosh
AU - Pankratz, Nathan
AU - Pankow, James S.
AU - Shah, Sonia
AU - Taylor, Kira
AU - Barnard, John
AU - Peters, Bas J.
AU - Maloney, Cliona M.
AU - Lobmeyer, Maximilian T.
AU - Stanton, Alice
AU - Zafarmand, M. Hadi
AU - Romaine, Simon P. R.
AU - Mehta, Amar
AU - van Iperen, Erik P. A.
AU - Gong, Yan
AU - Price, Tom S.
AU - Smith, Erin N.
AU - Kim, Cecilia E.
AU - Li, Yun R.
AU - Asselbergs, Folkert W.
AU - Atwood, Larry D.
AU - Bailey, Kristian M.
AU - Bhatt, Deepak
AU - Bauer, Florianne
AU - Behr, Elijah R.
AU - Bhangale, Tushar
AU - Boer, Jolanda M. A.
AU - Boehm, Bernhard O.
AU - Bradfield, Jonathan P.
AU - Brown, Morris
AU - Braund, Peter S.
AU - Burton, Paul R.
AU - Carty, Cara
AU - Chandrupatla, Hareesh R.
AU - Chen, Wei
AU - Connell, John
AU - Dalgeorgou, Chrysoula
AU - de Boer, Anthonius
AU - Drenos, Fotios
AU - Elbers, Clara C.
AU - Fang, James C.
AU - Fox, Caroline S.
AU - Frackelton, Edward C.
AU - Fuchs, Barry
AU - Furlong, Clement E.
AU - Gibson, Quince
AU - Gieger, Christian
AU - Goel, Anuj
AU - Grobbee, Diederik E.
AU - Hastie, Claire
AU - Howard, Philip J.
AU - Huang, Guan-Hua
AU - Johnson, W. Craig
AU - Li, Qing
AU - Kleber, Marcus E.
AU - Klein, Barbara E. K.
AU - Klein, Ronald
AU - Kooperberg, Charles
AU - Ky, Bonnie
AU - LaCroix, Andrea
AU - Lanken, Paul
AU - Lathrop, Mark
AU - Li, Mingyao
AU - Marshall, Vanessa
AU - Melander, Olle
AU - Mentch, Frank D.
AU - Meyer, Nuala J.
AU - Monda, Keri L.
AU - Montpetit, Alexandre
AU - Murugesan, Gurunathan
AU - Nakayama, Karen
AU - Nondahl, Dave
AU - Onipinla, Abiodun
AU - Rafelt, Suzanne
AU - Newhouse, Stephen J.
AU - Otieno, F. George
AU - Patel, Sanjey R.
AU - Putt, Mary E.
AU - Rodriguez, Santiago
AU - Safa, Radwan N.
AU - Sawyer, Douglas B.
AU - Schreiner, Pamela J.
AU - Simpson, Claire
AU - Sivapalaratnam, Suthesh
AU - Srinivasan, Sathanur R.
AU - Suver, Christine
AU - Swergold, Gary
AU - Sweitzer, Nancy K.
AU - Thomas, Kelly A.
AU - Thorand, Barbara
AU - Timpson, Nicholas J.
AU - Tischfield, Sam
AU - Tobin, Martin
AU - Tomaszewski, Maciej
AU - Tomaszweski, Maciej
AU - Verschuren, W. M. Monique
AU - Wallace, Chris
AU - Winkelmann, Bernhard
AU - Zhang, Haitao
AU - Zheng, Dongling
AU - Zhang, Li
AU - Zmuda, Joseph M.
AU - Clarke, Robert
AU - Balmforth, Anthony J.
AU - Danesh, John
AU - Day, Ian N.
AU - Schork, Nicholas J.
AU - de Bakker, Paul I. W.
AU - Delles, Christian
AU - Duggan, David
AU - Hingorani, Aroon D.
AU - Hirschhorn, Joel N.
AU - Hofker, Marten H.
AU - Humphries, Steve E.
AU - Kivimaki, Mika
AU - Lawlor, Debbie A.
AU - Kottke-Marchant, Kandice
AU - Mega, Jessica L.
AU - Mitchell, Braxton D.
AU - Morrow, David A.
AU - Palmen, Jutta
AU - Redline, Susan
AU - Shields, Denis C.
AU - Shuldiner, Alan R.
AU - Sleiman, Patrick M.
AU - Smith, George Davey
AU - Farrall, Martin
AU - Jamshidi, Yalda
AU - Christiani, David C.
AU - Casas, Juan P.
AU - Hall, Alistair S.
AU - Doevendans, Pieter A.
AU - Christie, Jason D.
AU - Berenson, Gerald S.
AU - Murray, Sarah S.
AU - Illig, Thomas
AU - Dorn, Gerald W.
AU - Cappola, Thomas P.
AU - Boerwinkle, Eric
AU - Sever, Peter
AU - Rader, Daniel J.
AU - Reilly, Muredach P.
AU - Caulfield, Mark
AU - Talmud, Philippa J.
AU - Topol, Eric
AU - Engert, James C.
AU - Wang, Kai
AU - Dominiczak, Anna
AU - Hamsten, Anders
AU - Curtis, Sean P.
AU - Silverstein, Roy L.
AU - Lange, Leslie A.
AU - Sabatine, Marc S.
AU - Trip, Mieke
AU - Saleheen, Danish
AU - Peden, John F.
AU - Cruickshanks, Karen J.
AU - März, Winfried
AU - O'Connell, Jeffrey R.
AU - Klungel, Olaf H.
AU - Wijmenga, Cisca
AU - Maitland-van der Zee, Anke Hilse
AU - Schadt, Eric E.
AU - Johnson, Julie A.
AU - Jarvik, Gail P.
AU - Papanicolaou, George J.
AU - Grant, Struan F. A.
AU - Munroe, Patricia B.
AU - North, Kari E.
AU - Samani, Nilesh J.
AU - Koenig, Wolfgang
AU - Gaunt, Tom R.
AU - Anand, Sonia S.
AU - van der Schouw, Yvonne T.
AU - Soranzo, Nicole
AU - FitzGerald, Garret A.
AU - Reiner, Alex
AU - Hegele, Robert A.
AU - Hakonarson, Hakon
AU - Keating, Brendan J.
PY - 2011
Y1 - 2011
N2 - 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 × 10(-6)), with 42 loci surpassing the conventional genome-wide significance threshold (p < 5 × 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 × 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
AB - 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 × 10(-6)), with 42 loci surpassing the conventional genome-wide significance threshold (p < 5 × 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 × 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
U2 - https://doi.org/10.1016/j.ajhg.2010.11.007
DO - https://doi.org/10.1016/j.ajhg.2010.11.007
M3 - Article
C2 - 21194676
SN - 0002-9297
VL - 88
SP - 6
EP - 18
JO - American journal of human genetics
JF - American journal of human genetics
IS - 1
ER -