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Linkage analysis of adult height in a large pedigree from a Dutch genetically isolated population

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Abstract

Despite extensive research of genetic determinants of human adult height, the genes identified up until now allow to predict only a small proportion of the trait’s variance. To identify new genes we analyzed 2,486 genotyped and phenotyped individuals in a large pedigree including 23,612 members in 18 generations. The pedigree was derived from a young genetically isolated Dutch population, where genetic heterogeneity is expected to be low and linkage disequilibrium has been shown to be increased. Complex segregation analysis confirmed high heritability of adult height, and suggested mixed model of height inheritance in this population. The estimates of the model parameters obtained from complex segregation analysis were used in parametric linkage analysis, which highlighted three genome-wide significant and additionally at least four suggestive loci involved in height. Significant peaks were located at the chromosomal regions 1p32 (LOD score = 3.35), 2p16 (LOD score = 3.29) and 16q24 (LOD score = 3.94). For the latter region, a strong association signal (FDR q < 0.05) was obtained for 19 SNPs, 17 of them were located in the CDH13 (cadherin 13) gene of which one (rs1035569) explained 1.5% of the total height variance.

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Acknowledgments

This work was supported by the Netherlands Organization for Scientific Research (NWO-RFBR 047.017.043), Russian Foundation for Basic Research (RFBR 07-04-00120-a), the NGI Center of Medical Systems Biology and Programs of RAS “Biosphere Origin and Evolution” and “Biodiversity”.

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Authors and Affiliations

  1. Institute of Cytology and Genetics SD RAS, Russian Academy of Science, Lavrentyev ave. 10, 630090, Novosibirsk, Russia

    Tatiana I. Axenovich, I. V. Zorkoltseva, N. M. Belonogova, A. V. Kirichenko & Y. S. Aulchenko

  2. Department of Cytology and Genetics, Novosibirsk State University, 630090, Novosibirsk, Russia

    Tatiana I. Axenovich & N. M. Belonogova

  3. Department of Forensic Molecular Biology, Erasmus University Medical Center Rotterdam, 3000 CA, Rotterdam, The Netherlands

    M. V. Struchalin & M. Kayser

  4. Department of Epidemiology, Erasmus University Medical Center Rotterdam, 3000 CA, Rotterdam, The Netherlands

    M. V. Struchalin, B. A. Oostra, C. M. van Duijn & Y. S. Aulchenko

Authors
  1. Tatiana I. Axenovich
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  2. I. V. Zorkoltseva
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  3. N. M. Belonogova
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  4. M. V. Struchalin
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  5. A. V. Kirichenko
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  6. M. Kayser
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  7. B. A. Oostra
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  8. C. M. van Duijn
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  9. Y. S. Aulchenko
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Corresponding author

Correspondence to Tatiana I. Axenovich.

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Axenovich, T.I., Zorkoltseva, I.V., Belonogova, N.M. et al. Linkage analysis of adult height in a large pedigree from a Dutch genetically isolated population. Hum Genet 126, 457–471 (2009). https://doi.org/10.1007/s00439-009-0686-x

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  • DOI: https://doi.org/10.1007/s00439-009-0686-x

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