Genetic identification of a common collagen disease in Puerto Ricans via identity-by-descent mapping in a health system
oleh: 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 EA Stahl, Judy H Cho, Ruth JF Loos, Erwin P Bottinger, Girish N Nadkarni, Noura S Abul-Husn, Eimear E Kenny
| Format: | Article |
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| Diterbitkan: | eLife Sciences Publications Ltd 2017-09-01 |
Deskripsi
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 multi-ethnic 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.