Genetic identification of a common collagen disease in puerto ricans via identity-by-descent mapping in a health system

Gillian Morven Belbin, Jacqueline Odgis, Elena P. Sorokin, Muh Ching Yee, Sumita Kohli, Benjamin S. Glicksberg, Christopher R. Gignoux, Genevieve L. Wojcik, Tielman Van Vleck, Janina M. Jeff, Michael Linderman, Claudia Schurmann, Douglas Ruderfer, Xiaoqiang Cai, Amanda Merkelson, Anne E. Justice, Kristin L. Young, Misa Graff, Kari E. North, Ulrike PetersRegina James, Lucia Hindorff, Ruth Kornreich, Lisa Edelmann, Omri Gottesman, Eli E.A. Stahl, Judy H. Cho, Ruth J.F. Loos, Erwin P. Bottinger, Girish N. Nadkarni, Noura S. Abul-Husn, Eimear E. Kenny

Research output: Contribution to journalArticle

Abstract

Achieving confidence in the causality of a disease locus is a complex task that often requires supporting data from both statistical genetics and clinical genomics. Here we describe a combined approach to identify and characterize a genetic disorder that leverages distantly related patients in a health system and population-scale mapping. We utilize genomic data to uncover components of distant pedigrees, in the absence of recorded pedigree information, in the multiethnic BioMe biobank in New York City. By linking to medical records, we discover a locus associated with both elevated genetic relatedness and extreme short stature. We link the gene, COL27A1, with a little-known genetic disease, previously thought to be rare and recessive. We demonstrate that disease manifests in both heterozygotes and homozygotes, indicating a common collagen disorder impacting up to 2% of individuals of Puerto Rican ancestry, leading to a better understanding of the continuum of complex and Mendelian disease.

Original languageEnglish (US)
Article numbere25060
JournaleLife
Volume6
DOIs
StatePublished - Sep 12 2017

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Belbin, G. M., Odgis, J., Sorokin, E. P., Yee, M. C., Kohli, S., Glicksberg, B. S., Gignoux, C. R., Wojcik, G. L., Van Vleck, T., Jeff, J. M., Linderman, M., Schurmann, C., Ruderfer, D., Cai, X., Merkelson, A., Justice, A. E., Young, K. L., Graff, M., North, K. E., ... Kenny, E. E. (2017). Genetic identification of a common collagen disease in puerto ricans via identity-by-descent mapping in a health system. eLife, 6, [e25060]. https://doi.org/10.7554/eLife.25060