Open AccessHigh Density GWAS for LDL Cholesterol in African Americans Using Electronic Medical Records Reveals a Strong Protective Variant in APOE
Author(s) -
RasmussenTorvik Laura J.,
Pacheco Jennifer A.,
Wilke Russell A.,
Thompson William K.,
Ritchie Marylyn D.,
Kho Abel N.,
Muthalagu Arun,
Hayes M. Geoff,
Armstrong Loren L.,
Scheftner Douglas A.,
Wilkins John T.,
Zuvich Rebecca L.,
Crosslin David,
Roden Dan M.,
Denny Joshua C.,
Jarvik Gail P.,
Carlson Christopher S.,
Kullo Iftikhar J.,
Bielinski Suzette J.,
McCarty Catherine A.,
Li Rongling,
Manolio Teri A.,
Crawford Dana C.,
Chisholm Rex L.
Publication year - 2012
Publication title -
clinical and translational science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.303
H-Index - 44
eISSN - 1752-8062
pISSN - 1752-8054
DOI - 10.1111/j.1752-8062.2012.00446.x
Subject(s) - genome wide association study , genotyping , snp , minor allele frequency , apolipoprotein e , medicine , single nucleotide polymorphism , genetic association , disease , genetics , biology , genotype , gene
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. Clin Trans Sci 2012; Volume 5: 394–399