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Elife. 2017 Sep 12;6. pii: e25060. doi: 10.7554/eLife.25060.

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

Author information

1
The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, United States.
2
Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, United States.
3
The Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, United States.
4
Department of Genetics, Stanford University School of Medicine, Stanford, United States.
5
Department of Plant Biology, Carnegie Institution for Science, Stanford, United States.
6
Harris Center for Precision Wellness, Icahn School of Medicine at Mt Sinai, New York, United States.
7
Broad Institute, Cambridge, United States.
8
Division of Psychiatric Genomics, Icahn School of Medicine at Mt Sinai, New York, United States.
9
Center for Statistical Genetics, Icahn School of Medicine at Mt Sinai, New York, United States.
10
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, United States.
11
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United States.
12
Department of Epidemiology, University of Washington School of Public Health, Seattle, United States.
13
National Institute on Minority Health and Health Disparities, National Institutes of Health, Bethesda, United States.
14
National Human Genome Research Institute, National Institutes of Health, Bethesda, United States.
15
Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, United States.
16
The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, United States.

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 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.

KEYWORDS:

Electronic Health Records; GWAS; collagen disorder; evolutionary biology; genomics; human; human biology; medical genetics; medicine; population genetics

PMID:
28895531
PMCID:
PMC5595434
DOI:
10.7554/eLife.25060
[Indexed for MEDLINE]
Free PMC Article

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