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Title: Meta-analysis of Dense Genecentric Association Studies Reveals Common and Uncommon Variants Associated with Height.
Authors: Lanktree, MB
Guo, Y
Murtaza, M
Glessner, JT
Bailey, SD
Onland-Moret, NC
Lettre, G
Ongen, H
Rajagopalan, R
Johnson, T
Shen, H
Nelson, CP
Klopp, N
Baumert, J
Padmanabhan, S
Pankratz, N
Pankow, JS
Shah, S
Taylor, K
Barnard, J
Peters, BJ
Maloney, CM
Lobmeyer, MT
Stanton, A
Zafarmand, MH
Romaine, SP
Mehta, A
van Iperen EP
Gong, Y
Price, TS
Smith, EN
Kim, CE
Li, YR
Asselbergs, FW
Atwood, LD
Bailey, KM
Bhatt, D
Bauer, F
Behr, ER
Bhangale, T
Boer, JM
Boehm, BO
Bradfield, JP
Brown, M
Braund, PS
Burton, PR
Carty, C
Chandrupatla, HR
Chen, W
Connell, J
Dalgeorgou, C
Boer, AD
Drenos, F
Elbers, CC
Fang, JC
Fox, CS
Frackelton, EC
Fuchs, B
Furlong, CE
Gibson, Q
Gieger, C
Goel, A
Grobbee, DE
Hastie, C
Howard, PJ
Huang, GH
Johnson, WC
Li, Q
Kleber, ME
Klein, BE
Klein, R
Kooperberg, C
Ky, B
Lacroix, A
Lanken, P
Lathrop, M
Li, M
Marshall, V
Melander, O
Mentch, FD
Meyer, NJ
Monda, KL
Montpetit, A
Murugesan, G
Nakayama, K
Nondahl, D
Onipinla, A
Rafelt, S
Newhouse, SJ
Otieno, FG
Patel, SR
Putt, ME
Rodriguez, S
Safa, RN
Sawyer, DB
Schreiner, PJ
Simpson, C
Sivapalaratnam, S
Srinivasan, SR
Suver, C
Swergold, G
Sweitzer, NK
Thomas, KA
Thorand, B
Timpson, NJ
Tischfield, S
Tobin, M
Tomaszewski, M
Verschuren, WM
Wallace, C
Winkelmann, B
Zhang, H
Zheng, D
Zhang, L
Zmuda, JM
Clarke, R
Balmforth, AJ
Danesh, J
Day, IN
Schork, NJ
de Bakker PI
Delles, C
Duggan, D
Hingorani, AD
Hirschhorn, JN
Hofker, MH
Humphries, SE
Kivimaki, M
Lawlor, DA
Kottke-Marchant, K
Mega, JL
Mitchell, BD
Morrow, DA
Palmen, J
Redline, S
Shields, DC
Shuldiner, AR
Sleiman, PM
Smith, GD
Farrall, M
Jamshidi, Y
Christiani, DC
Casas, JP
Hall, AS
Doevendans, PA
Christie, JD
Berenson, GS
Murray, SS
Illig, T
Dorn, GW
Cappola, TP
Boerwinkle, E
Sever, P
Rader, DJ
Reilly, MP
Caulfield, M
Talmud, PJ
Topol, E
Engert, JC
Wang, K
Dominiczak, A
Hamsten, A
Curtis, SP
Silverstein, RL
Lange, LA
Sabatine, MS
Trip, M
Saleheen, D
Peden, JF
Cruickshanks, KJ
März, W
O'Connell, JR
Klungel, OH
Wijmenga, C
Maitland-van der Zee AH
Schadt, EE
Johnson, JA
Jarvik, GP
Papanicolaou, GJ
Hugh Watkins on behalf of PROCARDIS
Grant, SF
Munroe, PB
North, KE
Samani, NJ
Koenig, W
Gaunt, TR
Anand, SS
van der Schouw YT
Meena Kumari on behalf of the Whitehall II Study and the WHII 50K Group
Soranzo, N
Fitzgerald, GA
Reiner, A
Hegele, RA
Hakonarson, H
Keating, BJ
First Published: 7-Jan-2011
Citation: AM J HUM GENET, 2011, 88 (1), pp. 6-18
Abstract: 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.
DOI Link: 10.1016/j.ajhg.2010.11.007
eISSN: 1537-6605
Type: Journal Article
Appears in Collections:Published Articles, Dept. of Health Sciences

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