Genetic Identification of a Common Collagen Disease in Puerto Ricans via Identity-by-Descent Mapping in a Health System
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 multi-ethnic BioMe biobank in New York City. By linking to medical records, we discover a locus associated with genetic relatedness that also underlies 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.
Subject Area
- Biochemistry (11703)
- Bioengineering (8718)
- Bioinformatics (29127)
- Biophysics (14930)
- Cancer Biology (12048)
- Cell Biology (17353)
- Clinical Trials (138)
- Developmental Biology (9406)
- Ecology (14143)
- Epidemiology (2067)
- Evolutionary Biology (18266)
- Genetics (12219)
- Genomics (16765)
- Immunology (11841)
- Microbiology (28003)
- Molecular Biology (11551)
- Neuroscience (60804)
- Paleontology (450)
- Pathology (1864)
- Pharmacology and Toxicology (3229)
- Physiology (4939)
- Plant Biology (10383)
- Synthetic Biology (2877)
- Systems Biology (7333)
- Zoology (1642)