Genomewide meta-analysis identifies loci associated with IGF-I and IGFBP-3 levels with impact on age-related traits

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MARC

Teumer, A.University of Greifswald (author)

Genomewide meta-analysis identifies loci associated with IGF-I and IGFBP-3 levels with impact on age-related traits

Article/chapterEnglish2016

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2016-06-21
Wiley,2016

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LIBRIS-ID:oai:gup.ub.gu.se/244481
https://gup.ub.gu.se/publication/244481URI
https://doi.org/10.1111/acel.12490DOI
https://lup.lub.lu.se/record/a6671480-24db-4d09-a28f-7c879806584fURI

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Language:English

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

The growth hormone/insulin-like growth factor (IGF) axis can be manipulated in animal models to promote longevity, and IGF-related proteins including IGF-I and IGF-binding protein-3 (IGFBP-3) have also been implicated in risk of human diseases including cardiovascular diseases, diabetes, and cancer. Through genomewide association study of up to 30 884 adults of European ancestry from 21 studies, we confirmed and extended the list of previously identified loci associated with circulating IGF-I and IGFBP-3 concentrations (IGF1, IGFBP3, GCKR, TNS3, GHSR, FOXO3, ASXL2, NUBP2/IGFALS, SORCS2, and CELSR2). Significant sex interactions, which were characterized by different genotype–phenotype associations between men and women, were found only for associations of IGFBP-3 concentrations with SNPs at the loci IGFBP3 and SORCS2. Analyses of SNPs, gene expression, and protein levels suggested that interplay between IGFBP3 and genes within the NUBP2 locus (IGFALS and HAGH) may affect circulating IGF-I and IGFBP-3 concentrations. The IGF-I-decreasing allele of SNP rs934073, which is an eQTL of ASXL2, was associated with lower adiposity and higher likelihood of survival beyond 90 years. The known longevity-associated variant rs2153960 (FOXO3) was observed to be a genomewide significant SNP for IGF-I concentrations. Bioinformatics analysis suggested enrichment of putative regulatory elements among these IGF-I- and IGFBP-3-associated loci, particularly of rs646776 at CELSR2. In conclusion, this study identified several loci associated with circulating IGF-I and IGFBP-3 concentrations and provides clues to the potential role of the IGF axis in mediating effects of known (FOXO3) and novel (ASXL2) longevity-associated loci. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Endokrinologi och diabetes hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Endocrinology and Diabetes hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Medicinsk genetik hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Medical Genetics hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Medicinsk bioteknologi Medicinsk bioteknologi hsv//swe
MEDICAL AND HEALTH SCIENCES Medical Biotechnology Medical Biotechnology hsv//eng
aging
genomewide association study
growth hormone axis
IGF-I
IGFBP-3
longevity

Added entries (persons, corporate bodies, meetings, titles ...)

Qi, Q.Yeshiva University,Harvard University (author)
Nethander, Maria,1980University of Gothenburg,Gothenburg University,Göteborgs universitet,Core Facilities, Bioinformatics,Centre for Bone and Arthritis Research,Core Facilities, Bioinformatics(Swepub:gu)xnetma (author)
Aschard, H.Harvard University,New York University,EURAC Research (author)
Bandinelli, S. (author)
Beekman, M.Leiden University Medical Centre (author)
Berndt, S. I.National Cancer Institute, USA,Boston University (author)
Bidlingmaier, M.Ludwig-Maximilian University of Munich (author)
Broer, L.Erasmus University Medical Center (author)
Cappola, A.University of Pennsylvania (author)
Ceda, G. P.University of Parma (author)
Chanock, S.University of Greifswald (author)
Chen, M. H.Boston University,University of Parma,Parma University Hospital (author)
Chen, T. C.Boston University,National Institute on Aging, United States (author)
Chen, Y. D. I.University of California, Los Angeles (author)
Chung, J.Yeshiva University (author)
Del Greco Miglianico, F.University of Lübeck,EURAC Research (author)
Eriksson, JoelUniversity of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xerjoe (author)
Ferrucci, L.National Institute on Aging, United States,Icahn School of Medicine at Mount Sinai (author)
Friedrich, N.University of Greifswald (author)
Gnewuch, C.University of Regensburg (author)
Goodarzi, M. O.Cedars-Sinai Medical Center (author)
Grarup, N.University of Copenhagen (author)
Guo, T.Yeshiva University (author)
Hammer, E.University of Greifswald (author)
Hayes, R. B. (author)
Hicks, A. A. (author)
Hofman, A.Erasmus University Medical Center (author)
Houwing-Duistermaat, J. J.Leiden University Medical Centre (author)
Hu, F.Harvard University (author)
Hunter, D. J.Harvard University (author)
Husemoen, L. L.Research Centre for Prevention and Health (author)
Isaacs, A.Leiden University Medical Centre,Erasmus University Medical Center (author)
Jacobs, K. B.University of Greifswald (author)
Lorentzon, Mattias,1970Gothenburg University,Göteborgs universitet,University of Gothenburg,Massachusetts General Hospital,Harvard University,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xlomat (author)
Jansson, John-Olov,1954University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology(Swepub:gu)xjanjo (author)
Jehmlich, N.University of Greifswald,Helmholtz Centre for Environmental Research (UFZ) (author)
Johnson, S.Yeshiva University (author)
Juul, A. (author)
Karlsson, MagnusLund University,Lunds universitet,Ortopedi - klinisk och molekylär osteoporosforskning,Forskargrupper vid Lunds universitet,Orthopedics - Clinical and Molecular Osteoporosis Research,Lund University Research Groups(Swepub:lu)orto-mka (author)
Kilpelainen, T. O.University of Copenhagen (author)
Kovacs, P.Leipzig University (author)
Kraft, P.Harvard University (author)
Li, C.Yeshiva University (author)
Linneberg, A. (author)
Liu, Y.Wake Forest University (author)
Loos, R. J. F. (author)
Lorentzon, Mattias,1970Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xlomat (author)
Lu, Y.Icahn School of Medicine at Mount Sinai (author)
Maggio, M.University of Washington, Seattle,Erasmus University Medical Center,Leiden University Medical Centre (author)
Magi, R.University of Oxford,University of Tartu (author)
Meigs, J. (author)
Mellström, Dan,1945University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xmelda (author)
Nauck, M.Harvard University,McGill University (author)
Newman, A. B.University of Pittsburgh (author)
Pollak, M. N. (author)
Pramstaller, P. P.EURAC Research,University of Lübeck,Leiden University Medical Centre (author)
Prokopenko, I.Imperial College London (author)
Psaty, B. M. (author)
Reincke, M.Ludwig-Maximilian University of Munich (author)
Rimm, E. B.Harvard University (author)
Rotter, J. I.University of California, Los Angeles (author)
Saint Pierre, A. (author)
Schurmann, C.Icahn School of Medicine at Mount Sinai (author)
Seshadri, S.Boston University (author)
Sjögren, Klara,1970University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xsjokl (author)
Slagboom, P. E. (author)
Strickler, H. D.Yeshiva University (author)
Stumvoll, M.Leipzig University (author)
Suh, Y.Guangdong Medical College,Yeshiva University (author)
Sun, Q. (author)
Zhang, C.National Institutes of Health, United States (author)
Svensson, Johan,1964University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xsjohc (author)
Tanaka, T. (author)
Tare, A.Yeshiva University (author)
Tönjes, A.Leipzig University (author)
Uh, H. W.Leiden University Medical Centre,University of Greifswald (author)
Van Duijn, C. M. (author)
van Heemst, D.Leiden University Medical Centre (author)
Vandenput, Liesbeth,1974University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xvanli (author)
Vasan, R. S. (author)
Völker, U.University of Greifswald (author)
Willems, Sara M. (author)
Ohlsson, Claes,1965University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xohlcl (author)
Wallaschofski, H. (author)
Kaplan, R. C.Yeshiva University (author)
University of GreifswaldYeshiva University (creator_code:org_t)

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In:Aging Cell: Wiley15:5, s. 811-8241474-97181474-9726

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By the author/editor: Teumer, A.; Qi, Q.; Nethander, Maria ...; Aschard, H.; Bandinelli, S.; Beekman, M.; show more...; Berndt, S. I.; Bidlingmaier, M.; Broer, L.; Cappola, A.; Ceda, G. P.; Chanock, S.; Chen, M. H.; Chen, T. C.; Chen, Y. D. I.; Chung, J.; Del Greco Miglia ...; Eriksson, Joel; Ferrucci, L.; Friedrich, N.; Gnewuch, C.; Goodarzi, M. O.; Grarup, N.; Guo, T.; Hammer, E.; Hayes, R. B.; Hicks, A. A.; Hofman, A.; Houwing-Duisterm ...; Hu, F.; Hunter, D. J.; Husemoen, L. L.; Isaacs, A.; Jacobs, K. B.; Lorentzon, Matti ...; Jansson, John-Ol ...; Jehmlich, N.; Johnson, S.; Juul, A.; Karlsson, Magnus; Kilpelainen, T. ...; Kovacs, P.; Kraft, P.; Li, C.; Linneberg, A.; Liu, Y.; Loos, R. J. F.; Lu, Y.; Maggio, M.; Magi, R.; Meigs, J.; Mellström, Dan, ...; Nauck, M.; Newman, A. B.; Pollak, M. N.; Pramstaller, P. ...; Prokopenko, I.; Psaty, B. M.; Reincke, M.; Rimm, E. B.; Rotter, J. I.; Saint Pierre, A.; Schurmann, C.; Seshadri, S.; Sjögren, Klara, ...; Slagboom, P. E.; Strickler, H. D.; Stumvoll, M.; Suh, Y.; Sun, Q.; Zhang, C.; Svensson, Johan, ...; Tanaka, T.; Tare, A.; Tönjes, A.; Uh, H. W.; Van Duijn, C. M.; van Heemst, D.; Vandenput, Liesb ...; Vasan, R. S.; Völker, U.; Willems, Sara M.; Ohlsson, Claes, ...; Wallaschofski, H ...; Kaplan, R. C.; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Endocrinology an ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medical Genetics

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Medical Biotechn ...; and Medical Biotechn ...

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