@article {1261,
	title = {A genome-wide association study identifies novel loci associated with circulating IGF-I and IGFBP-3.},
	journal = {Hum Mol Genet},
	volume = {20},
	year = {2011},
	month = {2011 Mar 15},
	pages = {1241-51},
	abstract = {<p>Insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein-3 (IGFBP-3) are involved in cell replication, proliferation, differentiation, protein synthesis, carbohydrate homeostasis and bone metabolism. Circulating IGF-I and IGFBP-3 concentrations predict anthropometric traits and risk of cancer and cardiovascular disease. In a genome-wide association study of 10 280 middle-aged and older men and women from four community-based cohort studies, we confirmed a known association of single nucleotide polymorphisms in the IGFBP3 gene region on chromosome 7p12.3 with IGFBP-3 concentrations using a significance threshold of P < 5 {\texttimes} 10(-8) (P = 3.3 {\texttimes} 10(-101)). Furthermore, the same IGFBP3 gene locus (e.g. rs11977526) that was associated with IGFBP-3 concentrations was also associated with the opposite direction of effect, with IGF-I concentration after adjustment for IGFBP-3 concentration (P = 1.9 {\texttimes} 10(-26)). A novel and independent locus on chromosome 7p12.3 (rs700752) had genome-wide significant associations with higher IGFBP-3 (P = 4.4 {\texttimes} 10(-21)) and higher IGF-I (P = 4.9 {\texttimes} 10(-9)) concentrations; when the two measurements were adjusted for one another, the IGF-I association was attenuated but the IGFBP-3 association was not. Two additional loci demonstrated genome-wide significant associations with IGFBP-3 concentration (rs1065656, chromosome 16p13.3, P = 1.2 {\texttimes} 10(-11), IGFALS, a confirmatory finding; and rs4234798, chromosome 4p16.1, P = 4.5 {\texttimes} 10(-10), SORCS2, a novel finding). Together, the four genome-wide significant loci explained 6.5\% of the population variation in IGFBP-3 concentration. Furthermore, we observed a borderline statistically significant association between IGF-I concentration and FOXO3 (rs2153960, chromosome 6q21, P = 5.1 {\texttimes} 10(-7)), a locus associated with longevity. These genetic loci deserve further investigation to elucidate the biological basis for the observed associations and clarify their possible role in IGF-mediated regulation of cell growth and metabolism.</p>},
	keywords = {Aged, Chromosomes, Human, Pair 7, Cohort Studies, European Continental Ancestry Group, Female, Genome-Wide Association Study, Humans, Insulin-Like Growth Factor Binding Protein 3, Insulin-Like Growth Factor I, Male, Polymorphism, Single Nucleotide},
	issn = {1460-2083},
	doi = {10.1093/hmg/ddq560},
	author = {Kaplan, Robert C and Petersen, Ann-Kristin and Chen, Ming-Huei and Teumer, Alexander and Glazer, Nicole L and D{\"o}ring, Angela and Lam, Carolyn S P and Friedrich, Nele and Newman, Anne and M{\"u}ller, Martina and Yang, Qiong and Homuth, Georg and Cappola, Anne and Klopp, Norman and Smith, Holly and Ernst, Florian and Psaty, Bruce M and Wichmann, H-Erich and Sawyer, Douglas B and Biffar, Reiner and Rotter, Jerome I and Gieger, Christian and Sullivan, Lisa S and V{\"o}lzke, Henry and Rice, Kenneth and Spyroglou, Ariadni and Kroemer, Heyo K and Ida Chen, Y-D and Manolopoulou, Jenny and Nauck, Matthias and Strickler, Howard D and Goodarzi, Mark O and Reincke, Martin and Pollak, Michael N and Bidlingmaier, Martin and Vasan, Ramachandran S and Wallaschofski, Henri}
}
