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 Peters; Regina 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

doi:10.7554/eLife.25060

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

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35 Scopus citations

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 language	English (US)
Article number	e25060
Journal	eLife
Volume	6
DOIs	https://doi.org/10.7554/eLife.25060
State	Published - Sep 12 2017
Externally published	Yes

ASJC Scopus subject areas

General Neuroscience
General Biochemistry, Genetics and Molecular Biology
General Immunology and Microbiology

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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, Article e25060. https://doi.org/10.7554/eLife.25060

Belbin, GM, Odgis, J, Sorokin, EP, Yee, MC, Kohli, S, Glicksberg, BS, Gignoux, CR, Wojcik, GL, Van Vleck, T, Jeff, JM, Linderman, M, Schurmann, C, Ruderfer, D, Cai, X, Merkelson, A, Justice, AE, Young, KL, Graff, M, North, KE, Peters, U, James, R, Hindorff, L, Kornreich, R, Edelmann, L, Gottesman, O, Stahl, EEA, Cho, JH, Loos, RJF, Bottinger, EP, Nadkarni, GN, Abul-Husn, NS & Kenny, EE 2017, 'Genetic identification of a common collagen disease in puerto ricans via identity-by-descent mapping in a health system', eLife, vol. 6, e25060. https://doi.org/10.7554/eLife.25060

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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.",

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AU - Belbin, Gillian Morven

AU - Odgis, Jacqueline

AU - Sorokin, Elena P.

AU - Yee, Muh Ching

AU - Kohli, Sumita

AU - Glicksberg, Benjamin S.

AU - Gignoux, Christopher R.

AU - Wojcik, Genevieve L.

AU - Van Vleck, Tielman

AU - Jeff, Janina M.

AU - Linderman, Michael

AU - Schurmann, Claudia

AU - Ruderfer, Douglas

AU - Cai, Xiaoqiang

AU - Merkelson, Amanda

AU - Justice, Anne E.

AU - Young, Kristin L.

AU - Graff, Misa

AU - North, Kari E.

AU - Peters, Ulrike

AU - James, Regina

AU - Hindorff, Lucia

AU - Kornreich, Ruth

AU - Edelmann, Lisa

AU - Gottesman, Omri

AU - Stahl, Eli E.A.

AU - Cho, Judy H.

AU - Loos, Ruth J.F.

AU - Bottinger, Erwin P.

AU - Nadkarni, Girish N.

AU - Abul-Husn, Noura S.

AU - Kenny, Eimear E.

PY - 2017/9/12

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

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ASJC Scopus subject areas

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