The 1p13.3 LDL-Associated Locus Shows Large Effect Sizes in Young Populations: 2920: Board #23 June 5 8:00 AM - 9:30 AM : Medicine & Science in Sports & Exercise

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G-34 Free Communication/Poster - Genetics: JUNE 5, 2010 7: 30 AM - 11: 00 AM: ROOM: Hall C

The 1p13.3 LDL-Associated Locus Shows Large Effect Sizes in Young Populations


Board #23 June 5 8:00 AM - 9:30 AM

Devaney, Joseph M.1; Thompson, Paul D. FACSM2; Visich, Paul S. FACSM3; Gordon, Paul M. FACSM4; Orkunoglu-Suer, Funda1; Gordish-Dressman, Heather1; Khianey, Rahul1; Hubal, Monica J.1; Clarkson, Priscilla M. FACSM5; Pescatello, Linda S. FACSM6; Zoeller, Robert F. FACSM7; Kraus, William E. FACSM8; Hoffman, Eric P.1

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Medicine & Science in Sports & Exercise 42(5):p 796, May 2010. | DOI: 10.1249/01.MSS.0000386462.00890.75
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Whole genome association studies (GWAS) have identified numerous significant polymorphic loci associated with selected coronary artery disease (CAD) risk factors such as serum lipids, body weight, and insulin resistance and in adult populations (42-69 yrs), but the relative contribution of each identified locus is minor contributing only 1 to 2% inter-individual variability.

PURPOSE: We hypothesized that younger populations would show a greater relative genetic component, due to fewer uncontrolled confounding variables such as physical activity and alcohol use.

METHODS: We examined the influence of 17 GWAS loci associated with serum lipids and insulin metabolism in two study cohorts: university students (FAMUSS; n=548; av. age= 24 yrs), and primary school students (CHIP; n=810, av. age= 11.5 yrs, all 6th graders).

RESULTS: 16 GWAS loci showed no relationship with their associated risk factor, but in young adults, the ancestral allele was associated with increased low density lipoprotein cholesterol (LDL) (TT: 97.6 ± 1.0 mg/dL [n=345], vs. CT/CC: 87.3 ± 1.0 mg/dL (n=203); p = 3 × 10-6), and was responsible for 3.6% of population variance in LDL levels (4.1% in females). 6th grade children showed a similar association with LDL (TT: 94.0 ± 1.3 mg/dL [n=551], vs. CT/CC: 84.7 ± 1.4 mg/dL [n=259]; p = 4 × 10-6), with 2.5% of the variance attributable to genotype.

CONCLUSION: These data show that the 1q13.3 GWAS locus is an early marker for LDL in children and young adults and suggest that the larger effect sizes observed in children and young adults compared to older populations might be due to the relative absence of cofounding variables. Our findings also suggest that the large majority of CAD risk factor loci (16/17) identified in adults are not operative in children. Strategies to reduce CAD risk factors in young individuals using genetic markers for early identification of susceptible subjects should be aware that genetic markers might differ in young and older populations. Also, identifying polymorphisms associated with CAD risk factors in children might facilitate earlier and thus more effective CAD prevention strategies.

© 2010 American College of Sports Medicine