TY - JOUR
T1 - The 1p13.3 LDL (C)-associated locus shows large effect sizes in young populations
AU - Devaney, Joseph M.
AU - Thompson, Paul D.
AU - Visich, Paul S.
AU - Saltarelli, William A.
AU - Gordon, Paul M.
AU - Orkunoglu-Suer, E. Funda
AU - Gordish-Dressman, Heather
AU - Harmon, Brennan T.
AU - Bradbury, Margaret K.
AU - Panchapakesan, Karuna
AU - Khianey, Rahul
AU - Hubal, Monica J.
AU - Clarkson, Priscilla M.
AU - Pescatello, Linda S.
AU - Zoeller, Robert F.
AU - Moyna, Niall M.
AU - Angelopoulos, Theodore J.
AU - Kraus, William E.
AU - Hoffman, Eric P.
PY - 2011/6
Y1 - 2011/6
N2 - Genome-wide association studies (GWASs) have identified polymorphic loci associated with coronary artery disease (CAD) risk factors (i.e. serum lipids) in adult populations (42-69 y). We hypothesized that younger populations would show a greater relative genetic component due to fewer confounding variables. We examined the influence of 20 GWAS loci associated with serum lipids and insulin metabolism, in a university student cohort (n = 548; mean age = 24 y), and replicated statistically associated results in a second study cohort of primary school students (n = 810, mean age = 11.5 y). Nineteen loci showed no relationship with studied risk factors in young adults. However, the ancestral allele of the rs646776 (SORT1) locus was strongly associated with increased LDL (C) in young adults [TT: 97.6 ± 1.0 mg/dL (n = 345) versus CT/CC: 87.3 ± 1.0 mg/dL (n = 203); p = 3 × 10] and children [TT: 94.0 ± 1.3 mg/dL (n = 551) versus CT/CC: 84.7 ± 1.4 mg/dL (n = 259); p = 4 × 10]. This locus is responsible for 3.6% of population variance in young adults and 2.5% of population variance in children. The effect size of the SORT1 locus is considerably higher in young populations (2.5-4.1%) compared with older subjects (1%).
AB - Genome-wide association studies (GWASs) have identified polymorphic loci associated with coronary artery disease (CAD) risk factors (i.e. serum lipids) in adult populations (42-69 y). We hypothesized that younger populations would show a greater relative genetic component due to fewer confounding variables. We examined the influence of 20 GWAS loci associated with serum lipids and insulin metabolism, in a university student cohort (n = 548; mean age = 24 y), and replicated statistically associated results in a second study cohort of primary school students (n = 810, mean age = 11.5 y). Nineteen loci showed no relationship with studied risk factors in young adults. However, the ancestral allele of the rs646776 (SORT1) locus was strongly associated with increased LDL (C) in young adults [TT: 97.6 ± 1.0 mg/dL (n = 345) versus CT/CC: 87.3 ± 1.0 mg/dL (n = 203); p = 3 × 10] and children [TT: 94.0 ± 1.3 mg/dL (n = 551) versus CT/CC: 84.7 ± 1.4 mg/dL (n = 259); p = 4 × 10]. This locus is responsible for 3.6% of population variance in young adults and 2.5% of population variance in children. The effect size of the SORT1 locus is considerably higher in young populations (2.5-4.1%) compared with older subjects (1%).
UR - https://www.scopus.com/pages/publications/79955809851
U2 - 10.1203/PDR.0b013e3182139227
DO - 10.1203/PDR.0b013e3182139227
M3 - Article
C2 - 21297524
AN - SCOPUS:79955809851
SN - 0031-3998
VL - 69
SP - 538
EP - 543
JO - Pediatric Research
JF - Pediatric Research
IS - 6
ER -