%0 Journal Article %J Elife %D 2017 %T Genetic identification of a common collagen disease in puerto ricans via identity-by-descent mapping in a health system. %A Belbin, Gillian Morven %A Odgis, Jacqueline %A Sorokin, Elena P %A Yee, Muh-Ching %A Kohli, Sumita %A Glicksberg, Benjamin S %A Gignoux, Christopher R %A Wojcik, Genevieve L %A Van Vleck, Tielman %A Jeff, Janina M %A Linderman, Michael %A Schurmann, Claudia %A Ruderfer, Douglas %A Cai, Xiaoqiang %A Merkelson, Amanda %A Justice, Anne E %A Young, Kristin L %A Graff, Misa %A North, Kari E %A Peters, Ulrike %A James, Regina %A Hindorff, Lucia %A Kornreich, Ruth %A Edelmann, Lisa %A Gottesman, Omri %A Stahl, Eli Ea %A Cho, Judy H %A Loos, Ruth Jf %A Bottinger, Erwin P %A Nadkarni, Girish N %A Abul-Husn, Noura S %A Kenny, Eimear E %K Adolescent %K Adult %K Aged %K Child %K Collagen Diseases %K Female %K Fibrillar Collagens %K Genotype %K Heterozygote %K Hispanic Americans %K Homozygote %K Humans %K Male %K Middle Aged %K Molecular Epidemiology %K Multigene Family %K Musculoskeletal Diseases %K New York City %K Pedigree %K Whole Genome Sequencing %K Young Adult %X

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 Bio 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, , 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.

%B Elife %V 6 %8 2017 09 12 %G eng %1 https://www.ncbi.nlm.nih.gov/pubmed/28895531?dopt=Abstract %R 10.7554/eLife.25060