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Novel association a...
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Moustafa, J. S. E.
(author)
Novel association approach for variable number tandem repeats (VNTRs) identifies DOCK5 as a susceptibility gene for severe obesity
- Article/chapterEnglish2012
Publisher, publication year, extent ...
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2012-05-16
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Oxford University Press (OUP),2012
Numbers
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LIBRIS-ID:oai:gup.ub.gu.se/164305
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https://gup.ub.gu.se/publication/164305URI
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https://doi.org/10.1093/hmg/dds187DOI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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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.
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Eleftherohorinou, H.
(author)
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de Smith, A. J.
(author)
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Andersson-Assarsson, Johanna C.,1974Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xanjoh
(author)
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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.
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Visvikis-Siest, S.
(author)
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Jacobson, Peter,1962Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xjacop
(author)
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Sjöström, LarsGothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xsjosl
(author)
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Carlsson, Lena M S,1957Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xcarle
(author)
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Walley, A.
(author)
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Falchi, M.
(author)
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Froguel, P.
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Blakemore, A. I. F.
(author)
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Coin, L. J. M.
(author)
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Göteborgs universitetInstitutionen för medicin, avdelningen för molekylär och klinisk medicin
(creator_code:org_t)
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In:Human Molecular Genetics: Oxford University Press (OUP)21:16, s. 3727-37380964-69061460-2083
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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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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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