Association Between Genetic Risks for Obesity and Working Memory in Children
Introduction: Obesity is highly heritable, and recent evidence demonstrates that obesity is associated with cognitive deficits, specifically working memory. However, the relationship between genetic risks for obesity and working memory is not clear. In addition, whether the effect of these genetic r...
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Frontiers Media S.A.
2021-09-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2021.749230/full |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nagahide Takahashi Nagahide Takahashi Nagahide Takahashi Tomoko Nishimura Tomoko Nishimura Taeko Harada Taeko Harada Akemi Okumura Akemi Okumura Toshiki Iwabuchi Toshiki Iwabuchi Md. Shafiur Rahman Md. Shafiur Rahman Hitoshi Kuwabara Shu Takagai Yoko Nomura Nori Takei Nori Takei Kenji J. Tsuchiya Kenji J. Tsuchiya |
spellingShingle |
Nagahide Takahashi Nagahide Takahashi Nagahide Takahashi Tomoko Nishimura Tomoko Nishimura Taeko Harada Taeko Harada Akemi Okumura Akemi Okumura Toshiki Iwabuchi Toshiki Iwabuchi Md. Shafiur Rahman Md. Shafiur Rahman Hitoshi Kuwabara Shu Takagai Yoko Nomura Nori Takei Nori Takei Kenji J. Tsuchiya Kenji J. Tsuchiya Association Between Genetic Risks for Obesity and Working Memory in Children Frontiers in Neuroscience polygenic risk score obesity cognition GWAS child development |
author_facet |
Nagahide Takahashi Nagahide Takahashi Nagahide Takahashi Tomoko Nishimura Tomoko Nishimura Taeko Harada Taeko Harada Akemi Okumura Akemi Okumura Toshiki Iwabuchi Toshiki Iwabuchi Md. Shafiur Rahman Md. Shafiur Rahman Hitoshi Kuwabara Shu Takagai Yoko Nomura Nori Takei Nori Takei Kenji J. Tsuchiya Kenji J. Tsuchiya |
author_sort |
Nagahide Takahashi |
title |
Association Between Genetic Risks for Obesity and Working Memory in Children |
title_short |
Association Between Genetic Risks for Obesity and Working Memory in Children |
title_full |
Association Between Genetic Risks for Obesity and Working Memory in Children |
title_fullStr |
Association Between Genetic Risks for Obesity and Working Memory in Children |
title_full_unstemmed |
Association Between Genetic Risks for Obesity and Working Memory in Children |
title_sort |
association between genetic risks for obesity and working memory in children |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Neuroscience |
issn |
1662-453X |
publishDate |
2021-09-01 |
description |
Introduction: Obesity is highly heritable, and recent evidence demonstrates that obesity is associated with cognitive deficits, specifically working memory. However, the relationship between genetic risks for obesity and working memory is not clear. In addition, whether the effect of these genetic risks on working memory in children is mediated by increased body mass index (BMI) has not been elucidated.Methods: In order to test whether the polygenic risk score (PRS) for obesity in adulthood (adulthood-BMI-PRS) is associated with working memory at 8 years of age, and whether the effect is mediated by childhood BMI, in children from the general population, participants in the Hamamatsu Birth Cohort for Mothers and Children (HBC) study in Hamamatsu, Japan, underwent testing for association of adulthood-BMI-PRS with working memory. HBC data collection began in December 2007 and is ongoing. Adulthood-BMI-PRS values were generated using summary data from the recent genome-wide association study (GWAS) undertaken in Japan, and the significance of thresholds was calculated for each outcome. Outcomes measured included the working memory index (WMI) of Weschler Intelligence Scale-4 (WISC-IV) scores and the BMI at 8 years of age. Gene-set enrichment analysis was conducted to clarify the molecular basis common to adulthood-BMI and childhood-WMI. Mediation analysis was performed to assess whether childhood-BMI of children mediated the association between adulthood-BMI-PRS and working memory.Results: A total of 734 participants (377 males, 357 females) were analyzed. Adulthood-BMI-PRS was associated with lower childhood-WMI (β[SE], −1.807 [0.668]; p = 0.010, corrected) of WISC-IV. Gene-set enrichment analyses found that regulation of neurotrophin Trk receptor signaling (β[SE], −2.020 [6.39]; p = 0.002, corrected), negative regulation of GTPase activity (β[SE], 2.001 [0.630]; p = 0.002, corrected), and regulation of gene expression epigenetic (β[SE], −2.119 [0.664]; p = 0.002, corrected) were enriched in BMI in adulthood and WMI in childhood. Mediation analysis showed that there is no mediation effect of childhood-BMI between the adulthood-BMI-PRS and working memory deficits in children.Conclusion: Adulthood-BMI-PRS was associated with working memory among children in the general population. These genetic risks were not mediated by the childhood-BMI itself and were directly associated with working memory deficits. |
topic |
polygenic risk score obesity cognition GWAS child development |
url |
https://www.frontiersin.org/articles/10.3389/fnins.2021.749230/full |
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doaj-69a24d0682654aa48f9996ee8602aa882021-09-22T04:36:20ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2021-09-011510.3389/fnins.2021.749230749230Association Between Genetic Risks for Obesity and Working Memory in ChildrenNagahide Takahashi0Nagahide Takahashi1Nagahide Takahashi2Tomoko Nishimura3Tomoko Nishimura4Taeko Harada5Taeko Harada6Akemi Okumura7Akemi Okumura8Toshiki Iwabuchi9Toshiki Iwabuchi10Md. Shafiur Rahman11Md. Shafiur Rahman12Hitoshi Kuwabara13Shu Takagai14Yoko Nomura15Nori Takei16Nori Takei17Kenji J. Tsuchiya18Kenji J. Tsuchiya19Department of Child and Adolescent Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, JapanResearch Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, JapanUnited Graduate School of Child Development, Hamamatsu University School of Medicine, Hamamatsu, JapanResearch Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, JapanUnited Graduate School of Child Development, Hamamatsu University School of Medicine, Hamamatsu, JapanResearch Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, JapanUnited Graduate School of Child Development, Hamamatsu University School of Medicine, Hamamatsu, JapanResearch Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, JapanUnited Graduate School of Child Development, Hamamatsu University School of Medicine, Hamamatsu, JapanResearch Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, JapanUnited Graduate School of Child Development, Hamamatsu University School of Medicine, Hamamatsu, JapanResearch Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, JapanUnited Graduate School of Child Development, Hamamatsu University School of Medicine, Hamamatsu, JapanDepartment of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, JapanDepartment of Child and Adolescent Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, JapanQueens College and Graduate Center, City University of New York, New York, NY, United StatesResearch Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, JapanUnited Graduate School of Child Development, Hamamatsu University School of Medicine, Hamamatsu, JapanResearch Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, JapanUnited Graduate School of Child Development, Hamamatsu University School of Medicine, Hamamatsu, JapanIntroduction: Obesity is highly heritable, and recent evidence demonstrates that obesity is associated with cognitive deficits, specifically working memory. However, the relationship between genetic risks for obesity and working memory is not clear. In addition, whether the effect of these genetic risks on working memory in children is mediated by increased body mass index (BMI) has not been elucidated.Methods: In order to test whether the polygenic risk score (PRS) for obesity in adulthood (adulthood-BMI-PRS) is associated with working memory at 8 years of age, and whether the effect is mediated by childhood BMI, in children from the general population, participants in the Hamamatsu Birth Cohort for Mothers and Children (HBC) study in Hamamatsu, Japan, underwent testing for association of adulthood-BMI-PRS with working memory. HBC data collection began in December 2007 and is ongoing. Adulthood-BMI-PRS values were generated using summary data from the recent genome-wide association study (GWAS) undertaken in Japan, and the significance of thresholds was calculated for each outcome. Outcomes measured included the working memory index (WMI) of Weschler Intelligence Scale-4 (WISC-IV) scores and the BMI at 8 years of age. Gene-set enrichment analysis was conducted to clarify the molecular basis common to adulthood-BMI and childhood-WMI. Mediation analysis was performed to assess whether childhood-BMI of children mediated the association between adulthood-BMI-PRS and working memory.Results: A total of 734 participants (377 males, 357 females) were analyzed. Adulthood-BMI-PRS was associated with lower childhood-WMI (β[SE], −1.807 [0.668]; p = 0.010, corrected) of WISC-IV. Gene-set enrichment analyses found that regulation of neurotrophin Trk receptor signaling (β[SE], −2.020 [6.39]; p = 0.002, corrected), negative regulation of GTPase activity (β[SE], 2.001 [0.630]; p = 0.002, corrected), and regulation of gene expression epigenetic (β[SE], −2.119 [0.664]; p = 0.002, corrected) were enriched in BMI in adulthood and WMI in childhood. Mediation analysis showed that there is no mediation effect of childhood-BMI between the adulthood-BMI-PRS and working memory deficits in children.Conclusion: Adulthood-BMI-PRS was associated with working memory among children in the general population. These genetic risks were not mediated by the childhood-BMI itself and were directly associated with working memory deficits.https://www.frontiersin.org/articles/10.3389/fnins.2021.749230/fullpolygenic risk scoreobesitycognitionGWASchild development |