Genomewide association study of leisure-time exercise behavior in Japanese Adults

Megumi Hara, Tsuyoshi Hachiya, Yoichi Sutoh, Keitaro Matsuo, Yuichiro Nishida, Chisato Shimanoe, Keitaro Tanaka, Atsushi Shimizu, Keizo Ohnaka, Takahisa Kawaguchi, Isao Oze, Fumihiko Matsuda, Hidemi Ito, Sayo Kawai, Asahi Hishida, Rieko Okada, Tae Sasakabe, Akie Hirata, Rie Ibusuki, Yora NinditaNorihiro Furusyo, Hiroaki Ikezaki, Nagato Kuriyama, Etsuko Ozaki, Haruo Mikami, Yohko Nakamura, Sadao Suzuki, Akihiro Hosono, Sakurako Katsuura-Kamano, Kokichi Arisawa, Kiyonori Kuriki, Kaori Endoh, Naoyuki Takashima, Aya Kadota, Masahiro Nakatochi, Yukihide Momozawa, Michiaki Kubo, Mariko Naito, Kenji Wakai

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Purpose Although several genetic factors may play a role in leisure-time exercise behavior, there is currently no evidence of a significant genomewide association, and candidate gene replication studies have produced inconsistent results. Methods We conducted a two-stage genomewide association study and candidate single-nucleotide polymorphisms (SNP) association study on leisure-time exercise behavior using 13,980 discovery samples from the Japan Multi-Institutional Collaborative Cohort (J-MICC) study, and 2036 replication samples from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center-2 study. Leisure-time physical activity was measured using a self-administered questionnaire that inquired about the type, frequency and duration of exercise. Participants with ≥4 MET·h·wk-1 of leisure-time physical activity were defined as exhibiting leisure-time exercise behavior. Association testing using mixed linear regression models was performed on the discovery and replication samples, after which the results were combined in a meta-analysis. In addition, we tested six candidate genetic variants derived from previous genomewide association study. Results We found that one novel SNP (rs10252228) located in the intergenic region between NPSR1 and DPY19L1 was significantly associated with leisure-time exercise behavior in discovery samples. This association was also significant in replication samples (combined P value by meta-analysis = 2.2 × 10-9). Several SNP linked with rs10252228 were significantly associated with gene expression of DPY19L1 and DP19L2P1 in skeletal muscle, heart, whole blood, and the nervous system. Among the candidate SNP, rs12612420 in DNAPTP6 demonstrated nominal significance in discovery samples but not in replication samples. Conclusions We identified a novel genetic variant associated with regular leisure-time exercise behavior. Further functional studies are required to validate the role of these variants in exercise behavior.

Original languageEnglish
Pages (from-to)2433-2441
Number of pages9
JournalMedicine and Science in Sports and Exercise
Volume50
Issue number12
DOIs
Publication statusPublished - 01-12-2018

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Leisure Activities
Exercise
Single Nucleotide Polymorphism
Meta-Analysis
Linear Models
Intergenic DNA
Genetic Association Studies
Nervous System
Japan
Skeletal Muscle
Cohort Studies
Gene Expression
Research
Neoplasms

All Science Journal Classification (ASJC) codes

  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Cite this

Hara, M., Hachiya, T., Sutoh, Y., Matsuo, K., Nishida, Y., Shimanoe, C., ... Wakai, K. (2018). Genomewide association study of leisure-time exercise behavior in Japanese Adults. Medicine and Science in Sports and Exercise, 50(12), 2433-2441. https://doi.org/10.1249/MSS.0000000000001712
Hara, Megumi ; Hachiya, Tsuyoshi ; Sutoh, Yoichi ; Matsuo, Keitaro ; Nishida, Yuichiro ; Shimanoe, Chisato ; Tanaka, Keitaro ; Shimizu, Atsushi ; Ohnaka, Keizo ; Kawaguchi, Takahisa ; Oze, Isao ; Matsuda, Fumihiko ; Ito, Hidemi ; Kawai, Sayo ; Hishida, Asahi ; Okada, Rieko ; Sasakabe, Tae ; Hirata, Akie ; Ibusuki, Rie ; Nindita, Yora ; Furusyo, Norihiro ; Ikezaki, Hiroaki ; Kuriyama, Nagato ; Ozaki, Etsuko ; Mikami, Haruo ; Nakamura, Yohko ; Suzuki, Sadao ; Hosono, Akihiro ; Katsuura-Kamano, Sakurako ; Arisawa, Kokichi ; Kuriki, Kiyonori ; Endoh, Kaori ; Takashima, Naoyuki ; Kadota, Aya ; Nakatochi, Masahiro ; Momozawa, Yukihide ; Kubo, Michiaki ; Naito, Mariko ; Wakai, Kenji. / Genomewide association study of leisure-time exercise behavior in Japanese Adults. In: Medicine and Science in Sports and Exercise. 2018 ; Vol. 50, No. 12. pp. 2433-2441.
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abstract = "Purpose Although several genetic factors may play a role in leisure-time exercise behavior, there is currently no evidence of a significant genomewide association, and candidate gene replication studies have produced inconsistent results. Methods We conducted a two-stage genomewide association study and candidate single-nucleotide polymorphisms (SNP) association study on leisure-time exercise behavior using 13,980 discovery samples from the Japan Multi-Institutional Collaborative Cohort (J-MICC) study, and 2036 replication samples from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center-2 study. Leisure-time physical activity was measured using a self-administered questionnaire that inquired about the type, frequency and duration of exercise. Participants with ≥4 MET·h·wk-1 of leisure-time physical activity were defined as exhibiting leisure-time exercise behavior. Association testing using mixed linear regression models was performed on the discovery and replication samples, after which the results were combined in a meta-analysis. In addition, we tested six candidate genetic variants derived from previous genomewide association study. Results We found that one novel SNP (rs10252228) located in the intergenic region between NPSR1 and DPY19L1 was significantly associated with leisure-time exercise behavior in discovery samples. This association was also significant in replication samples (combined P value by meta-analysis = 2.2 × 10-9). Several SNP linked with rs10252228 were significantly associated with gene expression of DPY19L1 and DP19L2P1 in skeletal muscle, heart, whole blood, and the nervous system. Among the candidate SNP, rs12612420 in DNAPTP6 demonstrated nominal significance in discovery samples but not in replication samples. Conclusions We identified a novel genetic variant associated with regular leisure-time exercise behavior. Further functional studies are required to validate the role of these variants in exercise behavior.",
author = "Megumi Hara and Tsuyoshi Hachiya and Yoichi Sutoh and Keitaro Matsuo and Yuichiro Nishida and Chisato Shimanoe and Keitaro Tanaka and Atsushi Shimizu and Keizo Ohnaka and Takahisa Kawaguchi and Isao Oze and Fumihiko Matsuda and Hidemi Ito and Sayo Kawai and Asahi Hishida and Rieko Okada and Tae Sasakabe and Akie Hirata and Rie Ibusuki and Yora Nindita and Norihiro Furusyo and Hiroaki Ikezaki and Nagato Kuriyama and Etsuko Ozaki and Haruo Mikami and Yohko Nakamura and Sadao Suzuki and Akihiro Hosono and Sakurako Katsuura-Kamano and Kokichi Arisawa and Kiyonori Kuriki and Kaori Endoh and Naoyuki Takashima and Aya Kadota and Masahiro Nakatochi and Yukihide Momozawa and Michiaki Kubo and Mariko Naito and Kenji Wakai",
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Hara, M, Hachiya, T, Sutoh, Y, Matsuo, K, Nishida, Y, Shimanoe, C, Tanaka, K, Shimizu, A, Ohnaka, K, Kawaguchi, T, Oze, I, Matsuda, F, Ito, H, Kawai, S, Hishida, A, Okada, R, Sasakabe, T, Hirata, A, Ibusuki, R, Nindita, Y, Furusyo, N, Ikezaki, H, Kuriyama, N, Ozaki, E, Mikami, H, Nakamura, Y, Suzuki, S, Hosono, A, Katsuura-Kamano, S, Arisawa, K, Kuriki, K, Endoh, K, Takashima, N, Kadota, A, Nakatochi, M, Momozawa, Y, Kubo, M, Naito, M & Wakai, K 2018, 'Genomewide association study of leisure-time exercise behavior in Japanese Adults', Medicine and Science in Sports and Exercise, vol. 50, no. 12, pp. 2433-2441. https://doi.org/10.1249/MSS.0000000000001712

Genomewide association study of leisure-time exercise behavior in Japanese Adults. / Hara, Megumi; Hachiya, Tsuyoshi; Sutoh, Yoichi; Matsuo, Keitaro; Nishida, Yuichiro; Shimanoe, Chisato; Tanaka, Keitaro; Shimizu, Atsushi; Ohnaka, Keizo; Kawaguchi, Takahisa; Oze, Isao; Matsuda, Fumihiko; Ito, Hidemi; Kawai, Sayo; Hishida, Asahi; Okada, Rieko; Sasakabe, Tae; Hirata, Akie; Ibusuki, Rie; Nindita, Yora; Furusyo, Norihiro; Ikezaki, Hiroaki; Kuriyama, Nagato; Ozaki, Etsuko; Mikami, Haruo; Nakamura, Yohko; Suzuki, Sadao; Hosono, Akihiro; Katsuura-Kamano, Sakurako; Arisawa, Kokichi; Kuriki, Kiyonori; Endoh, Kaori; Takashima, Naoyuki; Kadota, Aya; Nakatochi, Masahiro; Momozawa, Yukihide; Kubo, Michiaki; Naito, Mariko; Wakai, Kenji.

In: Medicine and Science in Sports and Exercise, Vol. 50, No. 12, 01.12.2018, p. 2433-2441.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genomewide association study of leisure-time exercise behavior in Japanese Adults

AU - Hara, Megumi

AU - Hachiya, Tsuyoshi

AU - Sutoh, Yoichi

AU - Matsuo, Keitaro

AU - Nishida, Yuichiro

AU - Shimanoe, Chisato

AU - Tanaka, Keitaro

AU - Shimizu, Atsushi

AU - Ohnaka, Keizo

AU - Kawaguchi, Takahisa

AU - Oze, Isao

AU - Matsuda, Fumihiko

AU - Ito, Hidemi

AU - Kawai, Sayo

AU - Hishida, Asahi

AU - Okada, Rieko

AU - Sasakabe, Tae

AU - Hirata, Akie

AU - Ibusuki, Rie

AU - Nindita, Yora

AU - Furusyo, Norihiro

AU - Ikezaki, Hiroaki

AU - Kuriyama, Nagato

AU - Ozaki, Etsuko

AU - Mikami, Haruo

AU - Nakamura, Yohko

AU - Suzuki, Sadao

AU - Hosono, Akihiro

AU - Katsuura-Kamano, Sakurako

AU - Arisawa, Kokichi

AU - Kuriki, Kiyonori

AU - Endoh, Kaori

AU - Takashima, Naoyuki

AU - Kadota, Aya

AU - Nakatochi, Masahiro

AU - Momozawa, Yukihide

AU - Kubo, Michiaki

AU - Naito, Mariko

AU - Wakai, Kenji

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Purpose Although several genetic factors may play a role in leisure-time exercise behavior, there is currently no evidence of a significant genomewide association, and candidate gene replication studies have produced inconsistent results. Methods We conducted a two-stage genomewide association study and candidate single-nucleotide polymorphisms (SNP) association study on leisure-time exercise behavior using 13,980 discovery samples from the Japan Multi-Institutional Collaborative Cohort (J-MICC) study, and 2036 replication samples from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center-2 study. Leisure-time physical activity was measured using a self-administered questionnaire that inquired about the type, frequency and duration of exercise. Participants with ≥4 MET·h·wk-1 of leisure-time physical activity were defined as exhibiting leisure-time exercise behavior. Association testing using mixed linear regression models was performed on the discovery and replication samples, after which the results were combined in a meta-analysis. In addition, we tested six candidate genetic variants derived from previous genomewide association study. Results We found that one novel SNP (rs10252228) located in the intergenic region between NPSR1 and DPY19L1 was significantly associated with leisure-time exercise behavior in discovery samples. This association was also significant in replication samples (combined P value by meta-analysis = 2.2 × 10-9). Several SNP linked with rs10252228 were significantly associated with gene expression of DPY19L1 and DP19L2P1 in skeletal muscle, heart, whole blood, and the nervous system. Among the candidate SNP, rs12612420 in DNAPTP6 demonstrated nominal significance in discovery samples but not in replication samples. Conclusions We identified a novel genetic variant associated with regular leisure-time exercise behavior. Further functional studies are required to validate the role of these variants in exercise behavior.

AB - Purpose Although several genetic factors may play a role in leisure-time exercise behavior, there is currently no evidence of a significant genomewide association, and candidate gene replication studies have produced inconsistent results. Methods We conducted a two-stage genomewide association study and candidate single-nucleotide polymorphisms (SNP) association study on leisure-time exercise behavior using 13,980 discovery samples from the Japan Multi-Institutional Collaborative Cohort (J-MICC) study, and 2036 replication samples from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center-2 study. Leisure-time physical activity was measured using a self-administered questionnaire that inquired about the type, frequency and duration of exercise. Participants with ≥4 MET·h·wk-1 of leisure-time physical activity were defined as exhibiting leisure-time exercise behavior. Association testing using mixed linear regression models was performed on the discovery and replication samples, after which the results were combined in a meta-analysis. In addition, we tested six candidate genetic variants derived from previous genomewide association study. Results We found that one novel SNP (rs10252228) located in the intergenic region between NPSR1 and DPY19L1 was significantly associated with leisure-time exercise behavior in discovery samples. This association was also significant in replication samples (combined P value by meta-analysis = 2.2 × 10-9). Several SNP linked with rs10252228 were significantly associated with gene expression of DPY19L1 and DP19L2P1 in skeletal muscle, heart, whole blood, and the nervous system. Among the candidate SNP, rs12612420 in DNAPTP6 demonstrated nominal significance in discovery samples but not in replication samples. Conclusions We identified a novel genetic variant associated with regular leisure-time exercise behavior. Further functional studies are required to validate the role of these variants in exercise behavior.

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DO - 10.1249/MSS.0000000000001712

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