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Genomics and personalized strategies in nutrition

A genome-wide association study on adherence to low-carbohydrate diets in Japanese

European Journal of Clinical Nutrition volume 76, pages 1103–1110 (2022)Cite this article

Subjects

Abstract

Background/objectives

Low-carbohydrate diets (LCD) are useful for weight reduction, and 50–55% carbohydrate consumption is associated with minimal risk. Genetic differences were related to nutritional consumption, food preferences, and dietary patterns, but whether particular genetic differences in individuals influence LCD adherence is unknown.

Subjects/methods

We conducted a GWAS on adherence to LCD utilizing 14,076 participants from the Japan Multi-Institutional Collaborative Cohort study. We used a previously validated semiquantitative food frequency questionnaire to estimate food consumption. Association of the imputed variants with the LCD score by Halton et al. we used linear regression analysis adjusting for sex, age, total dietary energy consumption, and components 1 to 10 by principal component analysis. We repeated the analysis with adjustment for alcohol consumption (g/day) in addition to the above-described variables.

Results

Men and women combined analysis without adjustment for alcohol consumption; we found 395 variants on chromosome 12 associated with the LCD score having P values <5 × 10−8. A conditional analysis with the addition of the dosage data of rs671 on chromosome 12 as a covariate, P values for all 395 SNPs on chromosome 12 turned out to be insignificant. In the analysis with additional adjustment for alcohol consumption, we did not identify any SNPs associated with the LCD score.

Conclusion

We found rs671 was inversely associated with adherence to LCD, but that was strongly confounded by alcohol consumption.

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Fig. 1: A quantile–quantile plot (black) of GWAS adjusting for sex, age, total dietary energy consumption (kcal/d), and PC 1–10.
Fig. 2: A Manhattan plot.
Fig. 3: A quantile–quantile plot (black) of genome-wide association studies with adjustment for sex, age, total dietary energy consumption (kcal/d), PC 1 to 10, and alcohol consumption (g/day).

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Acknowledgements

We would like to express our special thanks to all the faculty at RIKEN, the Laboratory for Genotyping Development, the Center for Integrative Medical Sciences, and the faculty of the BioBank Japan project. We would like to thank Drs. Nobuyuki Hamajima and Hideo Tanaka, the former principal investigators of the J-MICC, for their continuous support for our study. We also would like to thank Dr. Yoshiyuki Kita for his constant effort in promoting the J-MICC study.

Funding

This study was supported by JSPS KAKENHI Grants (No. 16H06277) from the Japanese Ministry of Education, Culture, Sports, Science, and Technology. And by a Grants-in-Aid for Scientific Research for Priority Areas of Cancer (No. 17015018) and Innovative Areas (No. 221S0001). It was also supported by the Ministry of Education, Culture, Sports, Science, and Technology from April 2003 to March 2015. and by funding for the BioBank Japan Project from the Japan Agency for Medical Research and Development from April 2015.

Author information

Authors and Affiliations

  1. Department of Public Health, Shiga University of Medical Science, Otsu, Japan

    Yasuyuki Nakamura, Naoyuki Takashima, Kenji Matsui, Naoko Miyagawa, Aya Kadota & Katsuyuki Miura

  2. Yamashina Racto Clinic and Medical Examination Center, Kyoto, Japan

    Yasuyuki Nakamura

  3. Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Takashi Tamura, Asahi Hishida, Mako Nagayoshi, Rieko Okada, Yoko Kubo, Kenji Takeuchi & Kenji Wakai

  4. Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan

    Akira Narita

  5. Division of Biomedical Information Analysis, Iwate Tohoku Medical Megabank Organization, Iwate Medical University, Shiwa-gun, Iwate, Japan

    Atsushi Shimizu & Yoichi Sutoh

  6. Division of Biomedical Information Analysis, Institute for Biomedical Sciences, Iwate Medical University, Shiwa-gun, Iwate, Japan

    Atsushi Shimizu

  7. Department of Public Health, Kindai University Faculty of Medicine, Osaka-Sayama, Japan

    Naoyuki Takashima

  8. Division of Bioethics and Healthcare Law, The National Cancer Center, Tokyo, Japan

    Kenji Matsui

  9. Department of Preventive Medicine and Public Health, Keio University School of Medicine, Tokyo, Japan

    Naoko Miyagawa

  10. NCD Epidemiology Research Center, Shiga University of Medical Science, Otsu, Japan

    Aya Kadota & Katsuyuki Miura

  11. Department of Psychosomatic Medicine, International University of Health and Welfare Narita Hospital, Narita, Japan

    Jun Otonari

  12. Department of Psychosomatic Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Jun Otonari

  13. Department of Comprehensive General Internal Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Hiroaki Ikezaki

  14. Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan

    Hiroaki Ikezaki

  15. Department of Preventive Medicine, Faculty of Medicine, Saga University, Saga, Japan

    Keitaro Tanaka

  16. Department of Pharmacy, Saga University Hospital, Saga, Japan

    Chisato Shimanoe

  17. School of Health Sciences, Faculty of Medicine, Kagoshima University, Kagoshima, Japan

    Rie Ibusuki & Daisaku Nishimoto

  18. Department of International Island and Community Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan

    Daisaku Nishimoto

  19. Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan

    Isao Oze

  20. Division of Cancer Information and Control, Aichi Cancer Center Research Institute, Nagoya, Japan

    Hidemi Ito

  21. Division of Descriptive Cancer Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Hidemi Ito

  22. Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Etsuko Ozaki & Daisuke Matsui

  23. Cancer Prevention Center, Chiba Cancer Center Research Institute, Chiba, Japan

    Haruo Mikami & Miho Kusakabe

  24. Department of Public Health, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

    Sadao Suzuki & Miki Watanabe

  25. Department of Preventive Medicine, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan

    Kokichi Arisawa & Sakurako Katsuura-Kamano

  26. Laboratory of Public Health, Division of Nutritional Sciences, School of Food and Nutritional Sciences, University of Shizuoka, Shizuoka, Japan

    Kiyonori Kuriki

  27. Public Health Informatics Unit, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Masahiro Nakatochi

  28. Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan

    Yukihide Momozawa & Michiaki Kubo

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  1. Yasuyuki Nakamura
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J-MICC Research Group Consortium

Contributions

YN, TT, and KW: designed the research; NT, KeM, NM, AK, KaM, JO, HIk, AH, MNag, RO, YK, KTan, CS, RI, DN, IO, HIt, EO, DM, HM, MKus, SS, MW, KA, SKK, KK, and KTak: conducted the research; YN, AN, AS, YS, MNak, YM, and MKub: analyzed data and performed statistical analysis; YN, TT, YS, and KW: wrote the paper and had primary responsibility for final content; and all authors: read and approved the final paper.

Corresponding author

Correspondence to Yasuyuki Nakamura.

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Nakamura, Y., Tamura, T., Narita, A. et al. A genome-wide association study on adherence to low-carbohydrate diets in Japanese. Eur J Clin Nutr 76, 1103–1110 (2022). https://doi.org/10.1038/s41430-022-01090-w

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