Session: FP01-Cell Specific GH & IGF-1 Signaling
Room 134 (Moscone Center)
Poster Board SAT-110
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
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