High Density GWAS for LDL Cholesterol in African Americans Using Electronic Medical Records Reveals a Strong Protective Variant in APOE

Laura J. Rasmussen-Torvik, Jennifer A. Pacheco, Russell A. Wilke, William K. Thompson, Marylyn D. Ritchie, Abel N. Kho, Arun Muthalagu, M. Geoff Hayes, Loren L. Armstrong, Douglas A. Scheftner, John T. Wilkins, Rebecca L. Zuvich, David Crosslin, Dan M. Roden, Joshua C. Denny, Gail P. Jarvik, Christopher S. Carlson, Iftikhar J. Kullo, Suzette J. Bielinski, Catherine A. MccartyRongling Li, Teri A. Manolio, Dana C. Crawford, Rex L. Chisholm

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Only one low-density lipoprotein cholesterol (LDL-C) genome-wide association study (GWAS) has been previously reported in -African Americans. We performed a GWAS of LDL-C in African Americans using data extracted from electronic medical records (EMR) in the eMERGE network. African Americans were genotyped on the Illumina 1M chip. All LDL-C measurements, prescriptions, and diagnoses of concomitant disease were extracted from EMR. We created two analytic datasets; one dataset having median LDL-C calculated after the exclusion of some lab values based on comorbidities and medication (n= 618) and another dataset having median LDL-C calculated without any exclusions (n= 1,249). SNP rs7412 in APOE was strongly associated with LDL-C in both datasets (p < 5 × 10-8). In the dataset with exclusions, a decrease of 20.0 mg/dL per minor allele was observed. The effect size was attenuated (12.3 mg/dL) in the dataset without any lab values excluded. Although other signals in APOE have been detected in previous GWAS, this large and important SNP association has not been well detected in large GWAS because rs7412 was not included on many genotyping arrays. Use of median LDL-C extracted from EMR after exclusions for medications and comorbidities increased the percentage of trait variance explained by genetic variation.

Original languageEnglish (US)
Pages (from-to)394-399
Number of pages6
JournalClinical and translational science
Volume5
Issue number5
DOIs
StatePublished - Oct 2012

Keywords

  • Electronic medical records
  • GWAS
  • LDL

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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    Rasmussen-Torvik, L. J., Pacheco, J. A., Wilke, R. A., Thompson, W. K., Ritchie, M. D., Kho, A. N., Muthalagu, A., Hayes, M. G., Armstrong, L. L., Scheftner, D. A., Wilkins, J. T., Zuvich, R. L., Crosslin, D., Roden, D. M., Denny, J. C., Jarvik, G. P., Carlson, C. S., Kullo, I. J., Bielinski, S. J., ... Chisholm, R. L. (2012). High Density GWAS for LDL Cholesterol in African Americans Using Electronic Medical Records Reveals a Strong Protective Variant in APOE. Clinical and translational science, 5(5), 394-399. https://doi.org/10.1111/j.1752-8062.2012.00446.x