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Novel association a...
Novel association approach for variable number tandem repeats (VNTRs) identifies DOCK5 as a susceptibility gene for severe obesity
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Moustafa, J. S. E. (author)
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Eleftherohorinou, H. (author)
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de Smith, A. J. (author)
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- Andersson-Assarsson, Johanna C., 1974 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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Alves, A. C. (author)
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Hadjigeorgiou, E. (author)
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Walters, R. G. (author)
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Asher, J. E. (author)
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Bottolo, L. (author)
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Buxton, J. L. (author)
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Sladek, R. (author)
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Meyre, D. (author)
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Dina, C. (author)
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Visvikis-Siest, S. (author)
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- Jacobson, Peter, 1962 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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- Sjöström, Lars (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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- Carlsson, Lena M S, 1957 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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Walley, A. (author)
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Falchi, M. (author)
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Froguel, P. (author)
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Blakemore, A. I. F. (author)
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Coin, L. J. M. (author)
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(creator_code:org_t)
- 2012-05-16
- 2012
- English.
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:16, s. 3727-3738
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https://academic.oup...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Variable number tandem repeats (VNTRs) constitute a relatively under-examined class of genomic variants in the context of complex disease because of their sequence complexity and the challenges in assaying them. Recent large-scale genome-wide copy number variant mapping and association efforts have highlighted the need for improved methodology for association studies using these complex polymorphisms. Here we describe the in-depth investigation of a complex region on chromosome 8p21.2 encompassing the dedicator of cytokinesis 5 (DOCK5) gene. The region includes two VNTRs of complex sequence composition which flank a common 3975 bp deletion, all three of which were genotyped by polymerase chain reaction and fragment analysis in a total of 2744 subjects. We have developed a novel VNTR association method named VNTRtest, suitable for association analysis of multi-allelic loci with binary and quantitative outcomes, and have used this approach to show significant association of the DOCK5 VNTRs with childhood and adult severe obesity (P-empirical 8.9 10(8) and P 3.1 10(3), respectively) which we estimate explains approximate to 0.8 of the phenotypic variance. We also identified an independent association between the 3975 base pair (bp) deletion and obesity, explaining a further 0.46 of the variance (P-combined 1.6 10(3)). Evidence for association between DOCK5 transcript levels and the 3975 bp deletion (P 0.027) and both VNTRs (P-empirical 0.015) was also identified in adipose tissue from a Swedish family sample, providing support for a functional effect of the DOCK5 deletion and VNTRs. These findings highlight the potential role of DOCK5 in human obesity and illustrate a novel approach for analysis of the contribution of VNTRs to disease susceptibility through association studies.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine (hsv//eng)
Keyword
- genome-wide association
- body-mass index
- copy number
- adipose-tissue
- complex diseases
- risk loci
- heritability
- polymorphism
- population
- expression
Publication and Content Type
- ref (subject category)
- art (subject category)
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Moustafa, J. S. ...
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Eleftherohorinou ...
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de Smith, A. J.
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Andersson-Assars ...
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Alves, A. C.
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Hadjigeorgiou, E ...
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show more...
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Walters, R. G.
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Asher, J. E.
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Bottolo, L.
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Buxton, J. L.
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Sladek, R.
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Meyre, D.
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Dina, C.
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Visvikis-Siest, ...
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Jacobson, Peter, ...
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Sjöström, Lars
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Carlsson, Lena M ...
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Walley, A.
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Falchi, M.
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Froguel, P.
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Blakemore, A. I. ...
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Coin, L. J. M.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
- Articles in the publication
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Human Molecular ...
- By the university
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University of Gothenburg