Genome-wide analysis of BMI in adolescents and young adults reveals additional insight into the effects of genetic loci over the life course.
Graff M., Ngwa JS., Workalemahu T., Homuth G., Schipf S., Teumer A., Völzke H., Wallaschofski H., Abecasis GR., Edward L., Francesco C., Sanna S., Scheet P., Schlessinger D., Sidore C., Xiao X., Wang Z., Chanock SJ., Jacobs KB., Hayes RB., Hu F., Van Dam RM., GIANT Consortium None., Crout RJ., Marazita ML., Shaffer JR., Atwood LD., Fox CS., Heard-Costa NL., White C., Choh AC., Czerwinski SA., Demerath EW., Dyer TD., Towne B., Amin N., Oostra BA., Van Duijn CM., Zillikens MC., Esko T., Nelis M., Nikopensius T., Metspalu A., Strachan DP., Monda K., Qi L., North KE., Cupples LA., Gordon-Larsen P., Berndt SI.
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.