Effects of gene-lifestyle interactions on obesity based on a multi-locus risk score: A cross-sectional analysis

Sho Nakamura; Xuemin Fang; Yoshinobu Saito; Hiroto Narimatsu; Azusa Ota; Hiroaki Ikezaki; Chisato Shimanoe; Keitaro Tanaka; Yoko Kubo; Mineko Tsukamoto; Takashi Tamura; Asahi Hishida; Isao Oze; Yuriko N Koyanagi; Yohko Nakamura; Miho Kusakabe; Toshiro Takezaki; Daisaku Nishimoto; Sadao Suzuki; Takahiro Otani; Nagato Kuriyama; Daisuke Matsui; Kiyonori Kuriki; Aya Kadota; Yasuyuki Nakamura; Kokichi Arisawa; Sakurako Katsuura-Kamano; Masahiro Nakatochi; Yukihide Momozawa; Michiaki Kubo; Kenji Takeuchi; Kenji Wakai

doi:10.1371/journal.pone.0279169

Effects of gene-lifestyle interactions on obesity based on a multi-locus risk score: A cross-sectional analysis

PLoS One. 2023 Feb 8;18(2):e0279169. doi: 10.1371/journal.pone.0279169. eCollection 2023.

Authors

Sho Nakamura^{1

2}, Xuemin Fang¹, Yoshinobu Saito^{2

3

4}, Hiroto Narimatsu^{1

2

3

5}, Azusa Ota⁶, Hiroaki Ikezaki^{6

7}, Chisato Shimanoe⁸, Keitaro Tanaka⁹, Yoko Kubo¹⁰, Mineko Tsukamoto¹⁰, Takashi Tamura¹⁰, Asahi Hishida¹⁰, Isao Oze¹¹, Yuriko N Koyanagi¹², Yohko Nakamura¹³, Miho Kusakabe¹³, Toshiro Takezaki¹⁴, Daisaku Nishimoto¹⁵, Sadao Suzuki¹⁶, Takahiro Otani¹⁶, Nagato Kuriyama^{17

18}, Daisuke Matsui¹⁷, Kiyonori Kuriki¹⁹, Aya Kadota²⁰, Yasuyuki Nakamura^{20

21}, Kokichi Arisawa²², Sakurako Katsuura-Kamano²², Masahiro Nakatochi²³, Yukihide Momozawa²⁴, Michiaki Kubo²⁴, Kenji Takeuchi^{10

25}, Kenji Wakai¹⁰

Affiliations

¹ Graduate School of Health Innovation, Kanagawa University of Human Services, Kawasaki, Kanagawa, Japan.
² Cancer Prevention and Control Division, Kanagawa Cancer Center Research Institute, Yokohama, Kanagawa, Japan.
³ Center for Innovation Policy, Kanagawa University of Human Services, Kawasaki, Kanagawa, Japan.
⁴ Faculty of Sport Management, Nippon Sport Science University, Yokohama, Kanagawa, Japan.
⁵ Department of Genetic Medicine, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan.
⁶ Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Fukuoka, Japan.
⁷ Department of Comprehensive General Internal Medicine, Faculty of Medical Sciences, Fukuoka, Fukuoka, Japan.
⁸ Department of Pharmacy, Saga University Hospital, Nabeshima, Saga, Japan.
⁹ Department of Preventive Medicine, Faculty of Medicine, Saga University, Nabeshima, Saga, Japan.
¹⁰ Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
¹¹ Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Aichi, Japan.
¹² Division of Cancer Information and Control, Aichi Cancer Center Research Institute, Nagoya, Aichi, Japan.
¹³ Cancer Prevention Center, Chiba Cancer Center Research Institute, Chiba, Chiba, Japan.
¹⁴ Department of International Island and Community Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Sakuragaoka, Kagoshima, Japan.
¹⁵ School of Health Sciences, Faculty of Medicine, Kagoshima University, Kagoshima, Kagoshima, Japan.
¹⁶ Department of Public Health, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
¹⁷ Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Nagoya, Aichi, Japan.
¹⁸ Shizuoka Graduate University of Public Health, Shizuoka, Shizuoka, Japan.
¹⁹ Laboratory of Public Health, Division of Nutritional Sciences, School of Food and Nutritional Sciences, University of Shizuoka, Shizuoka, Shizuoka, Japan.
²⁰ NCD Epidemiology Research Center, Shiga University of Medical Science, Otsu, Shiga, Japan.
²¹ Takeda Hospital Medical Examination Center, Kyoto, Kyoto, Japan.
²² Department of Preventive Medicine, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Tokushima, Japan.
²³ Public Health Informatics Unit, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
²⁴ Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan.
²⁵ Department of International and Community Oral Health, Tohoku University Graduate School of Dentistry, Sendai, Miyagi, Japan.

Abstract

Background: The relationship between lifestyle and obesity is a major focus of research. Personalized nutrition, which utilizes evidence from nutrigenomics, such as gene-environment interactions, has been attracting attention in recent years. However, evidence for gene-environment interactions that can inform treatment strategies is lacking, despite some reported interactions involving dietary intake or physical activity. Utilizing gene-lifestyle interactions in practice could aid in optimizing interventions according to genetic risk.

Methods: This study aimed to elucidate the effects of gene-lifestyle interactions on body mass index (BMI). Cross-sectional data from the Japan Multi-Institutional Collaborative Cohort Study were used. Interactions between a multi-locus genetic risk score (GRS), calculated from 76 ancestry-specific single nucleotide polymorphisms, and nutritional intake or physical activity were assessed using a linear mixed-effect model.

Results: The mean (standard deviation) BMI and GRS for all participants (n = 12,918) were 22.9 (3.0) kg/m2 and -0.07 (0.16), respectively. The correlation between GRS and BMI was r(12,916) = 0.13 (95% confidence interval [CI] 0.11-0.15, P < 0.001). An interaction between GRS and saturated fatty acid intake was observed (β = -0.11, 95% CI -0.21 to -0.02). An interaction between GRS and n-3 polyunsaturated fatty acids was also observed in the females with normal-weight subgroup (β = -0.12, 95% CI -0.22 to -0.03).

Conclusion: Our results provide evidence of an interaction effect between GRS and nutritional intake and physical activity. This gene-lifestyle interaction provides a basis for developing prevention or treatment interventions for obesity according to individual genetic predisposition.

Copyright: © 2023 Nakamura et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Body Mass Index
Cohort Studies
Cross-Sectional Studies
Female
Genetic Predisposition to Disease*
Humans
Life Style
Obesity* / genetics
Polymorphism, Single Nucleotide
Risk Factors

Grants and funding

This study was supported by Grants-in-Aid for Scientific Research for Priority Areas of Cancer (No. 17015018) and Innovative Areas (No. 221S0001) and by the Japan Society for the Promotion of Science (JSPS) KAKENHI Grant (No. 16H06277 [CoBiA]) from the Japanese Ministry of Education, Culture, Sports, Science and Technology. This work was also supported in part by funding for the BioBank Japan Project from the Japan Agency for Medical Research and Development since April 2015, and the Ministry of Education, Culture, Sports, Science and Technology from April 2003 to March 2015. There was no additional external funding received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.