title: The 1p13.3 LDL (C)-associated locus shows large effect sizes in young populations.
abstract: 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(x6)] 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(x6)]. 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%).
authors.affiliation: Department of Integrative Systems Biology, Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC 20010, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Devaney
authors.forename: Paul D
authors.initials: PD
authors.lastname: Thompson
authors.forename: Paul S
authors.initials: PS
authors.lastname: Visich
authors.forename: William A
authors.initials: WA
authors.lastname: Saltarelli
authors.forename: Paul M
authors.initials: PM
authors.lastname: Gordon
authors.forename: E Funda
authors.initials: EF
authors.lastname: Orkunoglu-Suer
authors.forename: Heather
authors.initials: H
authors.lastname: Gordish-Dressman
authors.forename: Brennan T
authors.initials: BT
authors.lastname: Harmon
authors.forename: Margaret K
authors.initials: MK
authors.lastname: Bradbury
authors.forename: Karuna
authors.initials: K
authors.lastname: Panchapakesan
authors.forename: Rahul
authors.initials: R
authors.lastname: Khianey
authors.forename: Monica J
authors.initials: MJ
authors.lastname: Hubal
authors.forename: Priscilla M
authors.initials: PM
authors.lastname: Clarkson
authors.forename: Linda S
authors.initials: LS
authors.lastname: Pescatello
authors.forename: Robert F
authors.initials: RF
authors.lastname: Zoeller
authors.forename: Niall M
authors.initials: NM
authors.lastname: Moyna
authors.forename: Theodore J
authors.initials: TJ
authors.lastname: Angelopoulos
authors.forename: William E
authors.initials: WE
authors.lastname: Kraus
authors.forename: Eric P
authors.initials: EP
authors.lastname: Hoffman
mesh_terms: D000328:Adult; D002648:Child; D008078:Cholesterol, LDL / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D003324:Coronary Artery Disease / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D015444:Exercise; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000378:metabolism; D008055:Lipids / Q000097:blood; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D055815:Young Adult
chemical_list: D008078:Cholesterol, LDL; D007328:Insulin; D008055:Lipids