DESCRIPTION:

List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was Insulin-like growth factors. The EFO term IGFBP-3 measurement was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.

LABEL:

GWAS: IGFBP-3 measurement

SCORE TYPE:

P-Value

DATE ADDED:

2017-05-02

DATE UPDATED:

2020-05-06

SPECIES:

AUTHORS:

RC Kaplan, AK Petersen, MH Chen, A Teumer, NL Glazer, A Döring, CS Lam, N Friedrich, A Newman, M Müller, Q Yang, G Homuth, A Cappola, N Klopp, H Smith, F Ernst, BM Psaty, HE Wichmann, DB Sawyer, R Biffar, JI Rotter, C Gieger, LS Sullivan, H Völzke, K Rice, A Spyroglou, HK Kroemer, YD Ida Chen, J Manolopoulou, M Nauck, HD Strickler, MO Goodarzi, M Reincke, MN Pollak, M Bidlingmaier, RS Vasan, H Wallaschofski

TITLE:

A genome-wide association study identifies novel loci associated with circulating IGF-I and IGFBP-3.

JOURNAL:

Human molecular genetics Mar 2011, Vol 20, pp. 1241-51

ABSTRACT:

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 × 10(-8) (P = 3.3 × 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 × 10(-26)). A novel and independent locus on chromosome 7p12.3 (rs700752) had genome-wide significant associations with higher IGFBP-3 (P = 4.4 × 10(-21)) and higher IGF-I (P = 4.9 × 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 × 10(-11), IGFALS, a confirmatory finding; and rs4234798, chromosome 4p16.1, P = 4.5 × 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 × 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. PUBMED: 21216879
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