TY - JOUR
T1 - Common variants in the JAZF1 gene associated with height identified by linkage and genome-wide association analysis
AU - EUROSPAN Consortium
AU - Johansson, Asa
AU - Marroni, Fabio
AU - Hayward, Caroline
AU - Franklin, Christopher S
AU - Kirichenko, Anatoly V
AU - Jonasson, Inger
AU - Hicks, Andrew A
AU - Vitart, Veronique
AU - Isaacs, Aaron
AU - Axenovich, Tatiana
AU - Campbell, Susan
AU - Dunlop, Malcolm G
AU - Floyd, Jamie
AU - Hastie, Nick
AU - Hofman, Albert
AU - Knott, Sara
AU - Kolcic, Ivana
AU - Pichler, Irene
AU - Polasek, Ozren
AU - Rivadeneira, Fernando
AU - Tenesa, Albert
AU - Uitterlinden, André G
AU - Wild, Sarah H
AU - Zorkoltseva, Irina V
AU - Meitinger, Thomas
AU - Wilson, James F
AU - Rudan, Igor
AU - Campbell, Harry
AU - Pattaro, Cristian
AU - Pramstaller, Peter
AU - Oostra, Ben A
AU - Wright, Alan F
AU - van Duijn, Cornelia M
AU - Aulchenko, Yurii S
AU - Gyllensten, Ulf
PY - 2009/1
Y1 - 2009/1
N2 - Genes for height have gained interest for decades, but only recently have candidate genes started to be identified. We have performed linkage analysis and genome-wide association for height in approximately 4000 individuals from five European populations. A total of five chromosomal regions showed suggestive linkage and in one of these regions, two SNPs (rs849140 and rs1635852) were associated with height (nominal P = 7.0 x 10(-8) and P = 9.6 x 10(-7), respectively). In total, five SNPs across the genome showed an association with height that reached the threshold of genome-wide significance (nominal P <1.6 x 10(-7)). The association with height was replicated for two SNPs (rs1635852 and rs849140) using three independent studies (n = 31 077, n=1268 and n = 5746) with overall meta P-values of 9.4 x 10(-10) and 5.3 x 10(-8). These SNPs are located in the JAZF1 gene, which has recently been associated with type II diabetes, prostate and endometrial cancer. JAZF1 is a transcriptional repressor of NR2C2, which results in low IGF1 serum concentrations, perinatal and early postnatal hypoglycemia and growth retardation when knocked out in mice. Both the linkage and association analyses independently identified the JAZF1 region affecting human height. We have demonstrated, through replication in additional independent populations, the consistency of the effect of the JAZF1 SNPs on height. Since this gene also has a key function in the metabolism of growth, JAZF1 represents one of the strongest candidates influencing human height identified so far.
AB - Genes for height have gained interest for decades, but only recently have candidate genes started to be identified. We have performed linkage analysis and genome-wide association for height in approximately 4000 individuals from five European populations. A total of five chromosomal regions showed suggestive linkage and in one of these regions, two SNPs (rs849140 and rs1635852) were associated with height (nominal P = 7.0 x 10(-8) and P = 9.6 x 10(-7), respectively). In total, five SNPs across the genome showed an association with height that reached the threshold of genome-wide significance (nominal P <1.6 x 10(-7)). The association with height was replicated for two SNPs (rs1635852 and rs849140) using three independent studies (n = 31 077, n=1268 and n = 5746) with overall meta P-values of 9.4 x 10(-10) and 5.3 x 10(-8). These SNPs are located in the JAZF1 gene, which has recently been associated with type II diabetes, prostate and endometrial cancer. JAZF1 is a transcriptional repressor of NR2C2, which results in low IGF1 serum concentrations, perinatal and early postnatal hypoglycemia and growth retardation when knocked out in mice. Both the linkage and association analyses independently identified the JAZF1 region affecting human height. We have demonstrated, through replication in additional independent populations, the consistency of the effect of the JAZF1 SNPs on height. Since this gene also has a key function in the metabolism of growth, JAZF1 represents one of the strongest candidates influencing human height identified so far.
UR - http://www.scopus.com/inward/record.url?scp=58049206782&partnerID=8YFLogxK
U2 - 10.1093/hmg/ddn350
DO - 10.1093/hmg/ddn350
M3 - Article
C2 - 18952825
SN - 0964-6906
VL - 18
SP - 373
EP - 380
JO - Human Molecular Genetics
JF - Human Molecular Genetics
IS - 2
ER -