FP01-5 Loci Related to Glucokinase and Insulin-Like Growth Factor Binding Are Associated With Circulating Levels of IGF-I and IGFBP-3

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP01-Cell Specific GH & IGF-1 Signaling
Saturday, June 15, 2013: 11:00 AM-11:30 AM
Presentation Start Time: 11:20 AM
Room 134 (Moscone Center)

Poster Board SAT-110
Alexander Teumer1, Vasan S Ramachandran2, Martin Bidlingmaier3, Toshiko Tanaka4, Nicole L Glazer2, Maria Nethander5, Tamara B Harris6, Marian Beekman7, Rudi G J Westendorp7, Eline Slagboom7, Jerome Rotter8, Peter P Pramstaller9, Qi Sun10, Cuilin Zhang11, Carolyn S.P. Lam2, Mark O Goodarzi8, Ken Rice12, Bruce M Psaty12, Guo Li12, James B Meigs13, Lewis Kuller14, Michael Pollak15, Cornelia van Duijn16, Anke Tönjes17, Sonja Berndt18, Elad Ziv19, Xiaonan Xue20, Claes Ohlsson21, Henri Wallaschofski*1 and Robert C Kaplan20
1University Medicine Greifswald, Greifswald, Germany, 2Boston University School of Medicine, Boston, MA, 3Ludwig-Maximilians University, Munich, Germany, 4National Institute on Aging, Baltimore, MD, 5University of Gothenburg, Gothenburg, Sweden, 6Natl Inst on Aging-NIH, Bethesda, MD, 7Leiden University Medical Center, Leiden, Netherlands, 8Cedars-Sinai Med Center, Los Angeles, CA, 9Center for Biomedicine, European Academy (EURAC); General Central Hospital Bozen, Italy; University of Lübeck, Germany, 10Harvard School of Public Health, Boston, MA, 11Eunice Kennedy Shriver National Institute for Child Health and Development, Bethesda, MD, 12University of Washington, Seattle, WA, 13MASS GENERAL HOSP and Med Schl, Boston, MA, 14University of Pittsburgh, Pittsburgh, PA, 15McGill Univ, Montreal, QC, Canada, 16Erasmus University Medical Center Rotterdam, Rotterdam, Netherlands, 17Universitätsklinikum Leipzig, Leipzig, Germany, 18National Cancer Institute, Bethesda, MD, 19Univ California San Francisco, San Francisco, CA, 20Albert Einstein College of Medicine, New York City, NY, 21Sahlgrenska Univ Hosp, Gothenburg, Sweden
Insulin-like growth factor-I (IGF-I) and its predominant carrier IGF binding protein 3 (IGFBP-3) are implicated in a complex biological system. Both are important in diverse biological processes including cell replication, proliferation or differentiation, protein synthesis, carbohydrate and bone metabolism. IGF-I and IGFBP-3 serum concentrations are associated with cardiovascular disease, cancer and all-cause mortality. IGF-I and IGFBP-3 levels are known to have a high degree of heritability.

We conducted a genome-wide association study (GWAS) of circulating concentrations of IGF-I and IGFBP-3 in a meta-analysis of up to 27,500 middle-aged adults of European ancestry. Analyses were adjusted for age and sex. We also investigated sex-specific associations. As most of the circulating IGF-I is bound to IGFBP-3, the concentration of free circulating IGF-I may be estimated by adjusting blood IGF-I concentrations for the concentrations of circulating IGFBP-3. Therefore, we also performed GWAS of IGF-I concentrations after adjustment for IGFBP-3 concentrations and vice versa.

In the combined analysis of men and women, we identified five new loci GCKR, IGF1, FOXO3, FAM148A and NUBP2 which reached genome-wide significance (p<5x10-8) for association with IGF-I, and one new locus CELSR2 which was associated with IGFBP-3 concentrations. SNPs near IGFBP3 showed effects on IGFBP-3 concentrations that differed by sex.

The findings revealed potential new loci which are related to glucokinase and insulin-like growth factor binding. Furthermore, the associations of known variants with both IGF-I and IGFBP-3 concentrations near IGFBP3 and TNS3 as well as the associations with IGFBP-3 concentrations in SORCS2 and in close vicinity of NUBP2/IGFALS were confirmed.

Disclosure: MB: Consultant, Immunodiagnostic Systems. Nothing to Disclose: AT, VSR, TT, NLG, MN, TBH, MB, RGJW, ES, JR, PPP, QS, CZ, CSPL, MOG, KR, BMP, GL, JBM, LK, MP, CV, AT, SB, EZ, XX, CO, HW, RCK

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm