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How body size is regulated: International study discovers ten new genes related to human growth

May 12, 2008

Scientists are beginning to unravel the question why people distinctly vary in size. In cooperation with scientists of the HelmholtzZentrum München, an international genome-wide study has discovered ten new genes that influence body height and thus provides new insights into biological pathways that are important for human growth.

This meta-analysis, published in the latest issue of Nature Genetics, is based on data from more than 26,000 study participants. It verifies two already known genes, but also discovered ten new genes. Altogether they explain a difference in body size of about 3.5 centimeters.

The analysis produced some biologically insightful findings. Several of the identified genes are targeted by the microRNA let-7, which affects the regulation of other genes. This connection was completely unknown until now. Several other SNPs may affect the structure of chromatin, the chromosome-surrounding proteins. Moreover, the results could have relevance for patients with inherited growth problems, or with problems in bone development, because some of the newly discovered genes have rare mutations, known to be associated with anomalous skeletal growth. Further functional studies are necessary to completely elucidate the biological mechanisms behind this growing list of genes related to height.

As German contribution to the meta-analysis, data from about 5,600 participants of the KORA study were analyzed by the HelmholtzZentrum scientists, Dr. Christian Gieger, Dr. Susana Eyheramendy, PD Dr. Thomas Illig, Dr. Iris M. Heid and Prof. Dr. Dr. H.-Erich Wichmann. In order to genotype 500,000 of the most frequent variants in the human genome, DNA chips were analyzed at the Institute for Human Genetics and the Institute of Epidemiology of the HelmholtzZentrum München under the direction of Prof. Dr. Thomas Meitinger. The coordinator of the study was Dr. Guillaume Lettre; Prof. Joel Hirschhorn acted as the principal investigator. Both scientists work at the Broad Institute of the MIT and the Harvard University, Cambridge. All investigators are part of the recently formed international consortium to study height and obesity-related traits (GIANT, Genetic Investigation of ANthropometric Traits).

Along with the results of a British study that was published simultaneously in Nature Genetics, the total number of known "height genes" now amounts to 26.

Literature:

Lettre G et al. Identification of ten loci associated with height and previously unknown biological pathways in human growth. Nature Genetics; 2008, 40(5): pp 584 - 591
Weedon MN et al. Genome-wide association analysis identified 20 loci that influence adult height. Nature Genetics; 2008, 40(5): pp 575 - 583

Helmholtz Zentrum München

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