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

Content Provider	PubMed Central
Author	Kaplan, Robert C. Petersen, Ann-kristin Chen, Ming-huei Teumer, Alexander Glazer, Nicole L. Döring, Angela Lam, Carolyn S. P. Friedrich, Nele Newman, Anne Müller, Martina Yang, Qiong Homuth, Georg Cappola, Anne Klopp, Norman Smith, Holly Ernst, Florian Psaty, Bruce M. Wichmann, H. Erich Sawyer, Douglas B. Biffar, Reiner Rotter, Jerome I. Gieger, Christian Sullivan, Lisa S. Henry, Völzke Rice, Kenneth Spyroglou, Ariadni Kroemer, Heyo K. Chen, Y. D. Ida Jenny, Manolopoulou Nauck, Matthias Strickler, Howard D. Goodarzi, Mark O. Reincke, Martin Pollak, Michael N. Martin, Bidlingmaier Vasan, Ramachandran S. Henri, Wallaschofski
Copyright Year	2011
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.
Related Links	http://dx.doi.org/10.1093/hmg/ddq560
Ending Page	1251
Page Count	11
Starting Page	1241
File Format	PDF
ISSN	09646906
e-ISSN	14602083
Journal	Human Molecular Genetics
Issue Number	6
Volume Number	20
Language	English
Publisher	Oxford University Press
Publisher Date	2011-03-15
Access Restriction	Open
Rights Holder	Oxford University Press
Subject Keyword	Genetics(clinical) Genetics Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Genetics Molecular Biology Genetics (clinical)

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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