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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 ...

  • 2012-05-16
  • Oxford University Press (OUP),2012

Numbers

  • LIBRIS-ID:oai:gup.ub.gu.se/164305
  • https://gup.ub.gu.se/publication/164305URI
  • https://doi.org/10.1093/hmg/dds187DOI

Supplementary language notes

  • Language:English

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

Notes

  • 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 and genre

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

  • Eleftherohorinou, H. (author)
  • de Smith, A. J. (author)
  • 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)
  • Alves, A. C. (author)
  • Hadjigeorgiou, E. (author)
  • Walters, R. G. (author)
  • Asher, J. E. (author)
  • Bottolo, L. (author)
  • Buxton, J. L. (author)
  • Sladek, R. (author)
  • Meyre, D. (author)
  • Dina, C. (author)
  • Visvikis-Siest, S. (author)
  • 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)
  • 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)
  • 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)
  • Walley, A. (author)
  • Falchi, M. (author)
  • Froguel, P. (author)
  • Blakemore, A. I. F. (author)
  • Coin, L. J. M. (author)
  • Göteborgs universitetInstitutionen för medicin, avdelningen för molekylär och klinisk medicin (creator_code:org_t)

Related titles

  • In:Human Molecular Genetics: Oxford University Press (OUP)21:16, s. 3727-37380964-69061460-2083

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