High density GWAS for LDL cholesterol in African Americans using electronic medical records reveals a strong protective variant in APOE.
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.
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. ljrtorvik@northwestern.edu
Laura J
LJ
Rasmussen-Torvik
Jennifer A
JA
Pacheco
Russell A
RA
Wilke
William K
WK
Thompson
Marylyn D
MD
Ritchie
Abel N
AN
Kho
Arun
A
Muthalagu
M Geoff
MG
Hayes
Loren L
LL
Armstrong
Douglas A
DA
Scheftner
John T
JT
Wilkins
Rebecca L
RL
Zuvich
David
D
Crosslin
Dan M
DM
Roden
Joshua C
JC
Denny
Gail P
GP
Jarvik
Christopher S
CS
Carlson
Iftikhar J
IJ
Kullo
Suzette J
SJ
Bielinski
Catherine A
CA
McCarty
Rongling
R
Li
Teri A
TA
Manolio
Dana C
DC
Crawford
Rex L
RL
Chisholm
D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D001057:Apolipoproteins E / Q000235:genetics*; D008078:Cholesterol, LDL / Q000235:genetics*; D057286:Electronic Health Records; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055815:Young Adult
D001057:Apolipoproteins E; D008078:Cholesterol, LDL