Genome-Wide Analysis of BMI in Adolescents and Young Adults Reveals Additional Insight into the Effects of Genetic Loci over the Life Course

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Citation

Graff, Mariaelisa; Ngwa, Julius S.; Workalemahu, Tsegaselassie; Homuth, Georg; Schipf, Sabine; Teumer, Alexander; Völzke, Henry; Wallaschofski, Henri; Abecasis, Gonçalo R.; & Edward, Lakatta, et al. (2013). Genome-Wide Analysis of BMI in Adolescents and Young Adults Reveals Additional Insight into the Effects of Genetic Loci over the Life Course. Human Molecular Genetics, 22(17), 3597-3607. PMCID: PMC3736869

Abstract

Genetic loci for body mass index (BMI) in adolescence and young adulthood, a period of high risk for weight gain, are understudied, yet may yield important insight into the etiology of obesity and early intervention. To identify novel genetic loci and examine the influence of known loci on BMI during this critical time period in late adolescence and early adulthood, we performed a two-stage meta-analysis using 14 genome-wide association studies in populations of European ancestry with data on BMI between ages 16 and 25 years in up to 29,880 individuals. We identified 7 independent loci (p< 5.0 x 10−8) near FTO (p=3.72x10−23), TMEM18 (p=3.24x10−17), MC4R (p=4.41x10−17), TNNI3 K (p=4.32x10−11), SEC16B (p=6.24x10−9), GNPDA2 (p=1.11x10−8), and POMC (p=4.94x10−8) as well as a potential secondary signal at the POMC locus (rs2118404, p=2.4 x 10−5 after conditioning on the established SNP at this locus) in adolescents and young adults. To evaluate the impact of the established genetic loci on BMI at these young ages, we examined differences between the effect sizes of 32 published BMI loci in European adult populations (aged 18 to 90 years) and those observed in our adolescent and young adult meta-analysis. Four loci (near PRKD1, TNNI3 K, SEC16B, and CADM2) had larger effects and 1 locus (near SH2B1) had a smaller effect on BMI during adolescence and young adulthood compared to older adults (p<0.05). These results suggest that genetic loci for BMI can vary in their effects across the life course, underlying the importance of evaluating BMI at different ages.

URL

http://dx.doi.org/10.1093/hmg/ddt205

Reference Type

Journal Article

Year Published

2013

Journal Title

Human Molecular Genetics

Author(s)

Graff, Mariaelisa
Ngwa, Julius S.
Workalemahu, Tsegaselassie
Homuth, Georg
Schipf, Sabine
Teumer, Alexander
Völzke, Henry
Wallaschofski, Henri
Abecasis, Gonçalo R.
Edward, Lakatta
Francesco, Cucca
Sanna, Serena
Scheet, Paul
Schlessinger, David
Sidore, Carlo
Xiao, Xiangjun
Wang, Zhaoming
Chanock, Stephen J.
Jacobs, Kevin B.
Hayes, Richard B.
Hu, Frank B.
Van Dam, Rob M.
The GIANT Consortium,
Crout, Richard J.
Marazita, Mary L.
Shaffer, John R.
Atwood, Larry D.
Fox, Caroline S.
Heard-Costa, Nancy L.
White, Charles C.
Choh, Audrey C.
Czerwinski, Stefan A.
Demerath, Ellen W.
Dyer, Thomas D.
Towne, Bradford
Amin, Najaf
Oostra, Ben A.
van Duijn, Cornelia M.
Zillikens, M. Carola
Esko, Tõnu
Nelis, Mari
Nikopensius, Tit
Metspalu, Andres
Strachan, David P.
Monda, Keri L.
Qi, Lu
North, Kari E.
Cupples, L. Adrienne
Gordon-Larsen, Penny
Berndt, Sonja I.

PMCID

PMC3736869

ORCiD

Gordon-Larsen - 0000-0001-5322-4188
Graff - 0000-0001-6380-1735