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Genetic mapping of a 17q chromosomal region linked to obesity phenotypes in the IRAS family study

International Journal of Obesity volume 30, pages 1433–1441 (2006)Cite this article

Abstract

Objective:

Obesity is widely accepted to be influenced by both environmental and genetic factors. Several recent studies have used the positional cloning approach in an attempt to discover genes contributing to obesity. In the IRAS Family Study a genomewide scan was performed on 1425 individuals of Hispanic descent (90 extended pedigree families) to identify regions of the genome linked to obesity phenotypes.

Methods:

Nonparametric QTL linkage analysis was performed using a variance components approach. The genome scan was performed in two phases: an initial genome scan in 45 families and a replication scan in 45 families. Fine mapping and candidate gene analyses were also performed. General estimating equations (GEE1) and quantitative pedigree disequilibrium tests (QPDT) were used for association analysis of single SNP and haplotype data.

Results:

Evidence for linkage to obesity traits was observed in each scan on the long arm of chromosome 17. When data from both scans was combined, a region on chromosome 17q was identified with evidence of linkage to visceral adipose tissue (VAT; LOD 3.11), waist circumference (WAIST) (LOD 2.5) and body mass index (BMI) (LOD 2.81). Nine additional microsatellite markers were identified and genotyped on all Hispanic individuals, with a mean marker density of approximately 1 marker/3 cM. Evidence of linkage remained significant with LOD 3.05 for VAT, LOD 2.44 for BMI and LOD 1.92 for WAIST. Fine mapping analyses suggest the possibility of two different obesity loci. In addition, the LOD – 1 interval of the major VAT peak decreased from 83–108 to 95–111 cM. Three positional candidate genes under the peak: somatostatin receptor 2 (SSTR2), galanin receptor 2 (GALR2), and growth hormone bound protein receptor 2 (GRB2) were chosen for detailed evaluation. Multiple polymorphisms within each candidate were genotyped and tested for association with the obesity phenotypes. Little evidence of association was detected between polymorphisms and obesity traits.

Conclusion:

In conclusion, replication of linkage and fine mapping suggest that a region on chromosome 17q contains a gene (or genes) that contributes to the genetic etiology of obesity with the strongest evidence for linkage to VAT. Candidate genes in the region do not appear to account for the evidence of linkage. Additional studies are necessary to identify the obesity-related polymorphisms.

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Acknowledgements

This research was supported in part by NIH grants HL060894, HL060931, HL060944, HL061019, and HL061210.

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Authors and Affiliations

  1. Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    B S Sutton & D W Bowden

  2. Centers for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    B S Sutton & D W Bowden

  3. Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    C D Langefeld, J K Campbell & L E Wagenknecht

  4. Department of Medicine, University of Texas Health Sciences Center at San Antonio, San Antonio, TX, USA

    S M Haffner

  5. Department of Preventive Medicine and Biometrics, University of Colorado Health Sciences Center, Denver, CO, USA

    J M Norris

  6. Department of Radiology, University of Colorado Health Sciences Center, Denver, CO, USA

    A L Scherzinger

  7. Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    D W Bowden

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  1. B S Sutton
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  2. C D Langefeld
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Correspondence to D W Bowden.

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Sutton, B., Langefeld, C., Campbell, J. et al. Genetic mapping of a 17q chromosomal region linked to obesity phenotypes in the IRAS family study. Int J Obes 30, 1433–1441 (2006). https://doi.org/10.1038/sj.ijo.0803298

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  • DOI: https://doi.org/10.1038/sj.ijo.0803298

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