Research Information System University of Greifswald

Graff M*, Ngwa J, Workalemahu T, Homuth G¹, Schipf S², Teumer A¹, Völzke H², Wallaschofski H³, Abecasis G, Edward L, Francesco C, Sanna S, Scheet P, Schlessinger D, Sidore C, Xiao X, Wang Z, Chanock S, Jacobs K, Hayes R, Hu F, Van Dam R, Crout R, Marazita M, Shaffer J, Atwood L, Fox C, Heard-Costa N, White C, Choh A, Czerwinski S, Demerath E, Dyer T, Towne B, Amin N, Oostra B, Van Duijn C, Zillikens M, Esko T, Nelis M, Nikopensius T, Metspalu A, Strachan D, Monda K, Qi L, North K, Cupples L, Gordon-Larsen P, Berndt S

1 - Interfakultäres Institut für Genetik und Funktionelle Genomforschung / Abt. Funktionelle Genomforschung

2 - Institut für Community Medicine / Abt. SHIP KEF

3 - Institut für Klinische Chemie und Laboratoriumsmedizin

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 in up to 29 880 individuals. We identified seven independent loci (P < 5.0 × 10(-8)) near FTO (P = 3.72 × 10(-23)), TMEM18 (P = 3.24 × 10(-17)), MC4R (P = 4.41 × 10(-17)), TNNI3K (P = 4.32 × 10(-11)), SEC16B (P = 6.24 × 10(-9)), GNPDA2 (P = 1.11 × 10(-8)) and POMC (P = 4.94 × 10(-8)) as well as a potential secondary signal at the POMC locus (rs2118404, P = 2.4 × 10(-5) after conditioning on the established single-nucleotide polymorphism 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 18-90) and those observed in our adolescent and young adult meta-analysis. Four loci (near PRKD1, TNNI3K, SEC16B and CADM2) had larger effects and one locus (near SH2B1) had a smaller effect on BMI during adolescence and young adulthood compared with 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.