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Association of the IGF1 gene with fasting insulin levels.

TitleAssociation of the IGF1 gene with fasting insulin levels.
Publication TypeJournal Article
Year of Publication2016
AuthorsWillems, SM, Cornes, BK, Brody, JA, Morrison, AC, Lipovich, L, Dauriz, M, Chen, Y, Liu, C-T, Rybin, DV, Gibbs, RA, Muzny, D, Pankow, JS, Psaty, BM, Boerwinkle, E, Rotter, JI, Siscovick, DS, Vasan, RS, Kaplan, RC, Isaacs, A, Dupuis, J, van Duijn, CM, Meigs, JB
JournalEur J Hum Genet
Date Published2016 Aug
Abstract<p>Insulin-like growth factor 1 (IGF-I) has been associated with insulin resistance. Genome-wide association studies (GWASs) of fasting insulin (FI) identified single-nucleotide variants (SNVs) near the IGF1 gene, raising two hypotheses: (1) these associations are mediated by IGF-I levels and (2) these noncoding variants either tag other functional variants in the region or are directly functional. In our study, analyses including 5141 individuals from population-based cohorts suggest that FI associations near IGF1 are not mediated by IGF-I. Analyses of targeted sequencing data in 3539 individuals reveal a large number of novel rare variants at the IGF1 locus and show a FI association with a subset of rare nonsynonymous variants (PSKAT=5.7 × 10(-4)). Conditional analyses suggest that this association is partly explained by the GWAS signal and the presence of a residual independent rare variant effect (Pconditional=0.019). Annotation using ENCODE data suggests that the GWAS variants may have a direct functional role in insulin biology. In conclusion, our study provides insight into variation present at the IGF1 locus and into the genetic architecture underlying FI levels, suggesting that FI associations of SNVs near IGF1 are not mediated by IGF-I and suggesting a role for both rare nonsynonymous and common functional variants in insulin biology.</p>
Alternate JournalEur. J. Hum. Genet.
PubMed ID26860063
PubMed Central IDPMC4989214
Grant ListK24 DK080140 / DK / NIDDK NIH HHS / United States
R01 DK078616 / DK / NIDDK NIH HHS / United States
U01 DK078616 / DK / NIDDK NIH HHS / United States