标题：Differential Effect of Polymorphisms on Body Mass Index Across the Life Course of Japanese: The Japan Multi-Institutional Collaborative Cohort Study
摘要：Background
Obesity is a reported risk factor for various health problems. Genome-wide association studies (GWASs) have identified numerous independent loci associated with body mass index (BMI). However, most of these have been focused on Europeans, and little evidence is available on the genetic effects across the life course of other ethnicities.
Methods
We conducted a cross-sectional study to examine the associations of 282 GWAS-identified single nucleotide polymorphisms with three BMI-related traits, current BMI, BMI at 20 years old (BMI at 20), and change in BMI (BMI change), among 11,586 Japanese individuals enrolled in the Japan Multi-Institutional Collaborative Cohort study. Associations were examined using multivariable linear regression models.
Results
We found a significant association (
P < 0.05/282 = 1.77 × 10
−4) between BMI and 11 polymorphisms in or near
FTO,
BDNF,
TMEM18,
HS6ST3, and
BORCS7. The trend was similar between current BMI and BMI change, but differed from that of the BMI at 20. Among the significant variants, those on
FTO were associated with all BMI traits, whereas those on
TMEM18 and
HS6SR3 were only associated with BMI at 20. The association of
FTO loci with BMI remained, even after additional adjustment for dietary energy intake.
Conclusions
Previously reported BMI-associated loci discovered in Europeans were also identified in the Japanese population. Additionally, our results suggest that the effects of each loci on BMI may vary across the life course and that this variation may be caused by the differential effects of individual genes on BMI via different pathways.
关键词：obesity;body mass index;genome wide association study;polymorphisms
