Abstract
BackgroundObesity 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.MethodsWe 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.ResultsWe 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.ConclusionsPreviously 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.
Highlights
Obesity is a known risk factor for various diseases[1,2,3] and has increased globally in recent decades
We examined three body mass index (BMI) traits: (i) current BMI, defined as the BMI calculated based on the selfreported current weight and current height; (ii) BMI at 20, defined as the BMI calculated based on the self-reported weight at 20 years old and current height; and (iii) BMI change, defined as=(age − 20)
Among the 282 candidate loci, we identified a total of 11 Single nucleotide polymorphisms (SNPs) with a statistically significant association with one or more BMI phenotypes in the adjusted analyses after applying the Bonferroni threshold
Summary
Obesity is a known risk factor for various diseases[1,2,3] and has increased globally in recent decades. Studies in twins and families suggest the existence of genetic factors for obesity.[4,5,6,7] In recent years, genome-wide association studies (GWASs) have identified genes for common traits and enabled the identification of numerous obesity-related genetic variants.[8,9,10,11] Among obesityrelated traits, body mass index (BMI) is a well-established measure for evaluating obesity,[12,13] and BMI-associated GWASs have reported a substantial number of related polymorphisms. Most of these have been focused on Europeans, and little evidence is available on the genetic effects across the life course of other ethnicities
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