Madoka Iwase1,2, Keitaro Matsuo1,3, Masahiro Nakatochi4, Isao Oze1, Hidemi Ito5,6, Yuriko Koyanagi5, Tomotaka Ugai1, Yumiko Kasugai1, Asahi Hishida7, Kenji Takeuchi7, Rieko Okada7, Yoko Kubo7, Chisato Shimanoe8, Keitaro Tanaka9, Hiroaki Ikezaki10, Masayuki Murata10, Toshiro Takezaki11, Daisaku Nishimoto12, Nagato Kuriyama13, Etsuko Ozaki13, Sadao Suzuki14, Miki Watanabe14, Haruo Mikami15, Yohko Nakamura15, Hirokazu Uemura16, Sakurako Katsuura-Kamano16, Kiyonori Kuriki17, Yoshikuni Kita18, Naoyuki Takashima19, Masato Nagino2, Yukihide Momozawa20, Michiaki Kubo21, Kenji Wakai6. 1. Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute. 2. Department of Surgical Oncology, Nagoya University Graduate School of Medicine. 3. Division of Cancer Epidemiology, Nagoya University Graduate School of Medicine. 4. Department of Nursing, Nagoya University Graduate School of Medicine. 5. Division of Cancer Information and Control, Aichi Cancer Center Research Institute. 6. Division of Descriptive Cancer Epidemiology, Nagoya University Graduate School of Medicine. 7. Department of Preventive Medicine, Nagoya University Graduate School of Medicine. 8. Clinical Research Center, Saga University Hospital. 9. Department of Preventive Medicine, Faculty of Medicine, Saga University. 10. Department of General Internal Medicine, Kyushu University Hospital. 11. Department of International Island and Community Medicine, Kagoshima University Graduate School of Medical and Dental Sciences. 12. School of Health Sciences, Faculty of Medicine, Kagoshima University. 13. Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine. 14. Department of Public Health, Nagoya City University Graduate School of Medical Sciences. 15. Cancer Prevention Center, Chiba Cancer Center Research Institute. 16. Department of Preventive Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School. 17. Laboratory of Public Health, University of Shizuoka. 18. Faculty of Nursing Science, Tsuruga Nursing University. 19. Department of Public Health, Faculty of Medicine, Kindai University. 20. Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences. 21. RIKEN Center for Integrative Medical Sciences.
Abstract
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.
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.
Entities:
Keywords:
body mass index; genome wide association study; obesity; polymorphisms