Does genetic predisposition modify the effect of lifestyle-related factors on DNA methylation?
Lifestyle-related phenotypes have been shown to be heritable and associated with DNA methylation. We aimed to investigate whether genetic predisposition to tobacco smoking, alcohol consumption, and higher body mass index (BMI) moderates the effect of these phenotypes on blood DNA methylation. We cal...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Epigenetics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/15592294.2022.2088038 |
| _version_ | 1827811465572122624 |
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| author | Chenglong Yu Allison M Hodge Ee Ming Wong Jihoon E Joo Enes Makalic Daniel F Schmidt Daniel D Buchanan Gianluca Severi John L Hopper Dallas R English Graham G Giles Roger L Milne Melissa C Southey Pierre-Antoine Dugué |
| author_facet | Chenglong Yu Allison M Hodge Ee Ming Wong Jihoon E Joo Enes Makalic Daniel F Schmidt Daniel D Buchanan Gianluca Severi John L Hopper Dallas R English Graham G Giles Roger L Milne Melissa C Southey Pierre-Antoine Dugué |
| author_sort | Chenglong Yu |
| collection | DOAJ |
| description | Lifestyle-related phenotypes have been shown to be heritable and associated with DNA methylation. We aimed to investigate whether genetic predisposition to tobacco smoking, alcohol consumption, and higher body mass index (BMI) moderates the effect of these phenotypes on blood DNA methylation. We calculated polygenic scores (PGS) to quantify genetic predisposition to these phenotypes using training (N = 7,431) and validation (N = 4,307) samples. Using paired genetic-methylation data (N = 4,307), gene–environment interactions (i.e., PGS × lifestyle) were assessed using linear mixed-effects models with outcomes: 1) methylation at sites found to be strongly associated with smoking (1,061 CpGs), alcohol consumption (459 CpGs), and BMI (85 CpGs) and 2) two epigenetic ageing measures, PhenoAge and GrimAge. In the validation sample, PGS explained ~1.4% (P = 1 × 10−14), ~0.6% (P = 2 × 10−7), and ~8.7% (P = 7 × 10−87) of variance in smoking initiation, alcohol consumption, and BMI, respectively. Nominally significant interaction effects (P < 0.05) were found at 61, 14, and 7 CpGs for smoking, alcohol consumption, and BMI, respectively. There was strong evidence that all lifestyle-related phenotypes were positively associated with PhenoAge and GrimAge, except for alcohol consumption with PhenoAge. There was weak evidence that the association of smoking with GrimAge was attenuated in participants genetically predisposed to smoking (interaction term: −0.022, standard error [SE] = 0.012, P = 0.058) and that the association of alcohol consumption with PhenoAge was attenuated in those genetically predisposed to drink alcohol (interaction term: −0.030, SE = 0.015, P = 0.041). In conclusion, genetic susceptibility to unhealthy lifestyles did not strongly modify the association between observed lifestyle behaviour and blood DNA methylation. Potential associations were observed for epigenetic ageing measures, which should be replicated in additional studies. |
| first_indexed | 2024-03-11T23:05:33Z |
| format | Article |
| id | doaj.art-7c18175c47c8433e906f51d2875295f1 |
| institution | Directory Open Access Journal |
| issn | 1559-2294 1559-2308 |
| language | English |
| last_indexed | 2024-03-11T23:05:33Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Epigenetics |
| spelling | doaj.art-7c18175c47c8433e906f51d2875295f12023-09-21T13:23:12ZengTaylor & Francis GroupEpigenetics1559-22941559-23082022-12-0117121838184710.1080/15592294.2022.20880382088038Does genetic predisposition modify the effect of lifestyle-related factors on DNA methylation?Chenglong Yu0Allison M Hodge1Ee Ming Wong2Jihoon E Joo3Enes Makalic4Daniel F Schmidt5Daniel D Buchanan6Gianluca Severi7John L Hopper8Dallas R English9Graham G Giles10Roger L Milne11Melissa C Southey12Pierre-Antoine Dugué13Monash UniversityCancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, AustraliaMonash UniversityThe University of MelbourneThe University of MelbourneThe University of MelbourneThe University of MelbourneFacultés de Médecine Universités Paris-Saclay, UvsqThe University of MelbourneCancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, AustraliaMonash UniversityMonash UniversityMonash UniversityMonash UniversityLifestyle-related phenotypes have been shown to be heritable and associated with DNA methylation. We aimed to investigate whether genetic predisposition to tobacco smoking, alcohol consumption, and higher body mass index (BMI) moderates the effect of these phenotypes on blood DNA methylation. We calculated polygenic scores (PGS) to quantify genetic predisposition to these phenotypes using training (N = 7,431) and validation (N = 4,307) samples. Using paired genetic-methylation data (N = 4,307), gene–environment interactions (i.e., PGS × lifestyle) were assessed using linear mixed-effects models with outcomes: 1) methylation at sites found to be strongly associated with smoking (1,061 CpGs), alcohol consumption (459 CpGs), and BMI (85 CpGs) and 2) two epigenetic ageing measures, PhenoAge and GrimAge. In the validation sample, PGS explained ~1.4% (P = 1 × 10−14), ~0.6% (P = 2 × 10−7), and ~8.7% (P = 7 × 10−87) of variance in smoking initiation, alcohol consumption, and BMI, respectively. Nominally significant interaction effects (P < 0.05) were found at 61, 14, and 7 CpGs for smoking, alcohol consumption, and BMI, respectively. There was strong evidence that all lifestyle-related phenotypes were positively associated with PhenoAge and GrimAge, except for alcohol consumption with PhenoAge. There was weak evidence that the association of smoking with GrimAge was attenuated in participants genetically predisposed to smoking (interaction term: −0.022, standard error [SE] = 0.012, P = 0.058) and that the association of alcohol consumption with PhenoAge was attenuated in those genetically predisposed to drink alcohol (interaction term: −0.030, SE = 0.015, P = 0.041). In conclusion, genetic susceptibility to unhealthy lifestyles did not strongly modify the association between observed lifestyle behaviour and blood DNA methylation. Potential associations were observed for epigenetic ageing measures, which should be replicated in additional studies.http://dx.doi.org/10.1080/15592294.2022.2088038dna methylationgene–environment interactionlifestylepolygenic scorecpg siteepigenetic ageing |
| spellingShingle | Chenglong Yu Allison M Hodge Ee Ming Wong Jihoon E Joo Enes Makalic Daniel F Schmidt Daniel D Buchanan Gianluca Severi John L Hopper Dallas R English Graham G Giles Roger L Milne Melissa C Southey Pierre-Antoine Dugué Does genetic predisposition modify the effect of lifestyle-related factors on DNA methylation? Epigenetics dna methylation gene–environment interaction lifestyle polygenic score cpg site epigenetic ageing |
| title | Does genetic predisposition modify the effect of lifestyle-related factors on DNA methylation? |
| title_full | Does genetic predisposition modify the effect of lifestyle-related factors on DNA methylation? |
| title_fullStr | Does genetic predisposition modify the effect of lifestyle-related factors on DNA methylation? |
| title_full_unstemmed | Does genetic predisposition modify the effect of lifestyle-related factors on DNA methylation? |
| title_short | Does genetic predisposition modify the effect of lifestyle-related factors on DNA methylation? |
| title_sort | does genetic predisposition modify the effect of lifestyle related factors on dna methylation |
| topic | dna methylation gene–environment interaction lifestyle polygenic score cpg site epigenetic ageing |
| url | http://dx.doi.org/10.1080/15592294.2022.2088038 |
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