title: Clinical Correlates of Autosomal Chromosomal Abnormalities in an Electronic Medical Record-Linked Genome-Wide Association Study: A Case Series.
abstract: Although mosaic autosomal chromosomal abnormalities are being increasingly detected as part of high-density genotyping studies, the clinical correlates are unclear. From an electronic medical record (EMR)-based genome-wide association study (GWAS) of peripheral arterial disease, log-R-ratio and B-allele-frequency data were used to identify mosaic autosomal chromosomal abnormalities including copy number variation and loss of heterozygosity. The EMRs of patients with chromosomal abnormalities and those without chromosomal abnormalities were reviewed to compare clinical characteristics. Among 3336 study participants, 0.75% (n = 25, mean age = 74.8 ± 10.7 years, 64% men) had abnormal intensity plots indicative of autosomal chromosomal abnormalities. A hematologic malignancy was present in 8 patients (32%), of whom 4 also had a solid organ malignancy while 2 patients had a solid organ malignancy only. In 50 age- and sex-matched participants without chromosomal abnormalities, there was a lower rate of hematologic malignancies (2% vs 32%,P< .001) but not solid organ malignancies (20% vs 24%,P= .69). We also report the clinical characteristics of each patient with the observed chromosomal abnormalities. Interestingly, among 5 patients with 20q deletions, 4 had a myeloproliferative disorder while all 3 men in this group had prostate cancer. In summary, in a GWAS of 3336 adults, 0.75% had autosomal chromosomal abnormalities and nearly a third of them had hematologic malignancies. A potential novel association between 20q deletions, myeloproliferative disorders, and prostate cancer was also noted.
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN.
authors.forename: Hayan
authors.initials: H
authors.lastname: Jouni
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN.
authors.forename: Khader
authors.initials: K
authors.lastname: Shameer
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN.
authors.forename: Yan W
authors.initials: YW
authors.lastname: Asmann
authors.affiliation: Department of Internal Medicine, Wayne State University, Detroit, MI.
authors.forename: Ribhi
authors.initials: R
authors.lastname: Hazin
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN.
authors.forename: Mariza
authors.initials: M
authors.lastname: de Andrade
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN.
authors.forename: Iftikhar J
authors.initials: IJ
authors.lastname: Kullo
keywords: copy number variation; genome-wide association studies; loss of heterozygosity; mosaic abnormalities; mosaic deletion; myeloproliferative disorders; prostate cancer; unipaternal disomy