TY - JOUR
T1 - Evaluation of the metabochip genotyping array in african americans and implications for fine mapping of gwas-identified loci
T2 - The PAGE study
AU - Buyske, Steven
AU - Wu, Ying
AU - Carty, Cara L.
AU - Cheng, Iona
AU - Assimes, Themistocles L.
AU - Dumitrescu, Logan
AU - Hindorff, Lucia A.
AU - Mitchell, Sabrina
AU - Ambite, Jose Luis
AU - Boerwinkle, Eric
AU - Buzkova, Petra
AU - Carlson, Chris S.
AU - Cochran, Barbara
AU - Duggan, David
AU - Eaton, Charles B.
AU - Fesinmeyer, Megan D.
AU - Franceschini, Nora
AU - Haessler, Jeffrey
AU - Jenny, Nancy
AU - Kang, Hyun Min
AU - Kooperberg, Charles
AU - Lin, Yi
AU - Marchand, Loic
AU - Matise, Tara C.
AU - Robinson, Jennifer G.
AU - Rodriguez, Carlos
AU - Schumacher, Fredrick R.
AU - Voight, Benjamin F.
AU - Young, Alicia
AU - Manolio, Teri A.
AU - Mohlke, Karen L.
AU - Haiman, Christopher A.
AU - Peters, Ulrike
AU - Crawford, Dana C.
AU - North, Kari E.
PY - 2012/4/23
Y1 - 2012/4/23
N2 - The Metabochip is a custom genotyping array designed for replication and fine mapping of metabolic, cardiovascular, and anthropometric trait loci and includes low frequency variation content identified from the 1000 Genomes Project. It has 196,725 SNPs concentrated in 257 genomic regions. We evaluated the Metabochip in 5,863 African Americans; 89% of all SNPs passed rigorous quality control with a call rate of 99.9%. Two examples illustrate the value of fine mapping with the Metabochip in African-ancestry populations. At CELSR2/PSRC1/SORT1, we found the strongest associated SNP for LDL-C to be rs12740374 (p = 3.5×10 -11), a SNP indistinguishable from multiple SNPs in European ancestry samples due to high correlation. Its distinct signal supports functional studies elsewhere suggesting a causal role in LDL-C. At CETP we found rs17231520, with risk allele frequency 0.07 in African Americans, to be associated with HDL-C (p = 7.2×10 -36). This variant is very rare in Europeans and not tagged in common GWAS arrays, but was identified as associated with HDL-C in African Americans in a single-gene study. Our results, one narrowing the risk interval and the other revealing an associated variant not found in Europeans, demonstrate the advantages of high-density genotyping of common and rare variation for fine mapping of trait loci in African American samples.
AB - The Metabochip is a custom genotyping array designed for replication and fine mapping of metabolic, cardiovascular, and anthropometric trait loci and includes low frequency variation content identified from the 1000 Genomes Project. It has 196,725 SNPs concentrated in 257 genomic regions. We evaluated the Metabochip in 5,863 African Americans; 89% of all SNPs passed rigorous quality control with a call rate of 99.9%. Two examples illustrate the value of fine mapping with the Metabochip in African-ancestry populations. At CELSR2/PSRC1/SORT1, we found the strongest associated SNP for LDL-C to be rs12740374 (p = 3.5×10 -11), a SNP indistinguishable from multiple SNPs in European ancestry samples due to high correlation. Its distinct signal supports functional studies elsewhere suggesting a causal role in LDL-C. At CETP we found rs17231520, with risk allele frequency 0.07 in African Americans, to be associated with HDL-C (p = 7.2×10 -36). This variant is very rare in Europeans and not tagged in common GWAS arrays, but was identified as associated with HDL-C in African Americans in a single-gene study. Our results, one narrowing the risk interval and the other revealing an associated variant not found in Europeans, demonstrate the advantages of high-density genotyping of common and rare variation for fine mapping of trait loci in African American samples.
UR - http://www.scopus.com/inward/record.url?scp=84860014014&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84860014014&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0035651
DO - 10.1371/journal.pone.0035651
M3 - Article
C2 - 22539988
AN - SCOPUS:84860014014
SN - 1932-6203
VL - 7
JO - PloS one
JF - PloS one
IS - 4
M1 - e35651
ER -