Apolipoprotein E epsilon 4 genotype and a physically active lifestyle in late life: analysis of gene–environment interaction for the risk of dementia and Alzheimer's disease dementia

2013 ◽  
Vol 44 (6) ◽  
pp. 1319-1329 ◽  
Author(s):  
T. Luck ◽  
S. G. Riedel-Heller ◽  
M. Luppa ◽  
B. Wiese ◽  
M. Köhler ◽  
...  
Keyword(s):  
Physical Activity ◽  
Alzheimer’S Disease ◽  
Apolipoprotein E ◽  
Late Life ◽  
Environment Interaction ◽  
Additive Interaction ◽  
Free Survival ◽  
Gene Environment Interaction ◽  
Gene Environment

BackgroundAs physical activity may modify the effect of the apolipoprotein E (APOE) ε4 allele on the risk of dementia and Alzheimer's disease (AD) dementia, we tested for such a gene–environment interaction in a sample of general practice patients aged ⩾75 years.MethodData were derived from follow-up waves I–IV of the longitudinal German study on Ageing, Cognition and Dementia in Primary Care Patients (AgeCoDe). The Kaplan–Meier survival method was used to estimate dementia- and AD-free survival times. Multivariable Cox regression was used to assess individual associations of APOE ε4 and physical activity with risk for dementia and AD, controlling for covariates. We tested for gene–environment interaction by calculating three indices of additive interaction.ResultsAmong the randomly selected sample of 6619 patients, 3327 (50.3%) individuals participated in the study at baseline and 2810 (42.5%) at follow-up I. Of the 2492 patients without dementia included at follow-up I, 278 developed dementia (184 AD) over the subsequent follow-up interval of 4.5 years. The presence of the APOE ε4 allele significantly increased and higher physical activity significantly decreased risk for dementia and AD. The co-presence of APOE ε4 with low physical activity was associated with higher risk for dementia and AD and shorter dementia- and AD-free survival time than the presence of APOE ε4 or low physical activity alone. Indices of interaction indicated no significant interaction between low physical activity and the APOE ε4 allele for general dementia risk, but a possible additive interaction for AD risk.ConclusionsPhysical activity even in late life may be effective in reducing conversion to dementia and AD or in delaying the onset of clinical manifestations. APOE ε4 carriers may particularly benefit from increasing physical activity with regard to their risk for AD.

scholarly journals Physical Activity as Moderator of the Association Between APOE and Cognitive Decline in Older Adults: Results from Three Longitudinal Cohort Studies

2020 ◽  
Vol 75 (10) ◽  
pp. 1880-1886
Author(s):  
Najada Stringa ◽  
Natasja M van Schoor ◽  
Yuri Milaneschi ◽  
M Arfan Ikram ◽  
Vieri Del Panta ◽  
...  
Keyword(s):  
Physical Activity ◽  
Older Adults ◽  
Cohort Studies ◽  
Cognitive Decline ◽  
Sex Education ◽  
Environment Interaction ◽  
Longitudinal Cohort ◽  
Gene Environment Interaction ◽  
Gene Environment

Abstract Background Previous studies have suggested that the association between APOE ɛ 4 and dementia is moderated by physical activity (PA), but the results remain inconclusive and longitudinal data on cognitive decline are missing. In this study, we examine whether there is a gene–environment interaction between APOE and PA on cognitive decline in older adults using 9-year follow-up data of three cohort studies. Methods We followed 7,176 participants from three longitudinal cohort studies: Longitudinal Aging Study Amsterdam (LASA), InCHIANTI, and Rotterdam Study for 9 years. PA was assessed with self-reported questionnaires and was categorized in low, moderate, and high PA. Cognitive function was assessed with the Mini-Mental State Examination (MMSE) and cognitive decline was defined as a decrease of three points or more on the MMSE during 3 years follow-up. We fitted logistic regression models using generalized estimating equations adjusting for age, sex, education, depressive symptoms, and number of chronic disease. Interaction between APOE and PA was tested on multiplicative and additive scale. Results Cohorts were similar in most aspects but InCHIANTI participants were on average older and had lower education. APOE ɛ 4 carriers had higher odds of cognitive decline (odds ratio [OR] = 1.46, 95% confidence interval [CI]: 1.29–1.64) while PA was not significantly associated with cognitive decline overall (moderate PA: OR = 0.87, 0.67–1.13; high PA: OR = 0.71, 0.36–1.40). There was no evidence for an interaction effect between PA and APOE ɛ 4 in cognitive decline in older adults (APOE × moderate PA: p = .83; APOE × high PA: p = .90). Conclusions Previous claims of a gene–environment interaction between APOE ɛ 4 and PA in cognitive decline are not supported by our results.

Association Between Tfeb Gene Polymorphism, Gene–environment Interaction, and Fatty Liver Disease: a Case–control Study in China

2021 ◽  
Author(s):  
Chunbao Mo ◽  
Tingyu Mai ◽  
Jiansheng Cai ◽  
Haoyu He ◽  
Huaxiang Lu ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Case Control Study ◽  
Case Control ◽  
Environment Interaction ◽  
Additive Interaction ◽  
Gene Environment Interaction ◽  
Gene Environment ◽  
Control Study

Abstract Background: Fatty liver disease (FLD) is a serious public health problem that is rapidly increasing. Evidences indicated that the transcription factor EB (TFEB) gene may be involved in the pathophysiology of FLD; however, whether TEFB polymorphism is association with FLD remains unclear.Objectives: To explore the association among TFEB polymorphism, gene–environment interaction, and FLD and provide epidemiological evidence for clarifying the genetic factors of FLD.Methods: This study is a case–control study. Sequenom MassARRAY was applied in genotyping. Logical regression was used to analyze the association between TFEB polymorphism and FLD, and the gene–environment interaction in FLD was evaluated by multiplication and additive interaction models.Results: (1) The alleles and genotypes of each single nucleotide polymorphism of TFEB in the case and control groups were evenly distributed; no statistically substantial difference was observed. (2) Logistic regression analysis indicated that TFEB polymorphism is not remarkably associated with FLD. (3) In the multiplicative interaction model, rs1015149, rs1062966, and rs11754668 had remarkable interaction with smoking amount. Rs1062966 and rs11754668 also had a considerable interaction with body mass index and alcohol intake, respectively. However, no remarkable additive interaction was observed.Conclusion: TFEB polymorphism is not directly associated with FLD susceptibility, but the risk can be changed through gene–environment interaction.

Genetic Counselling: Its Need in Psychiatry and the Directions it Gives for Future Research

1984 ◽  
Vol 29 (4) ◽  
pp. 289-294 ◽  
Author(s):  
Harvey C. Stancer ◽  
Diane K. Wagener
Keyword(s):  
Genetic Counselling ◽  
Social Worker ◽  
Future Research ◽  
Environment Interaction ◽  
Adoption Studies ◽  
Gene Environment Interaction ◽  
Empirical Risk ◽  
Gene Environment ◽  
The Social

The methods for investigating the extent to which genetic factors can influence vulnerability to psychiatric illness are, in increasing order of precision: family, twin, and adoption studies. The evidence from these studies is in support of a gene-environment interaction for schizophrenia and the affective disorders. While the family study method cannot supply precise etiological data, the empirically derived information can be used by the genetic counsellor to provide empirical risk estimates to the counsellee. The psychiatrist, geneticist, and social worker make an appropriate team for reliable genetic counselling. The clinician must determine the precise psychiatric diagnoses in family members which the geneticist may use to estimate risk. The social worker can follow-up the counselling session or sessions to assess the counsellees’ understanding of what has been told to them. It is stressed that while genetic counselling should be available, clinical judgement should be exercised to ensure its appropriate use.

scholarly journals Issues concerning feedback about genetic testing and risk of depression

2009 ◽  
Vol 194 (5) ◽  
pp. 404-410 ◽  
Author(s):  
Kay Wilhelm ◽  
Bettina Meiser ◽  
Philip B. Mitchell ◽  
Adam W. Finch ◽  
Jennifer E. Siegel ◽  
...  
Keyword(s):  
Serotonin Transporter ◽  
Causal Effect ◽  
Environment Interaction ◽  
Gene Environment Interaction ◽  
Individual Genotype ◽  
Gene Environment ◽  
Serotonin Transporter Genotype ◽  
S Allele ◽  
The Impact

BackgroundRecent studies show that adverse life events have a significantly greater impact on depression onset for those with the s/s allele of the genotype for the 5-HT gene-linked promoter region. Research in genes related to risk of depression leads to the question of how this information is received by individuals.AimsTo investigate factors related to the response to receiving one's own serotonin transporter genotype results.MethodPredictors of the impact of receiving individual genotype data were assessed in 128 participants in a study of gene–environment interaction in depression onset.ResultsTwo-thirds decided to learn their individual genotype results (receivers) and prior to disclosure this decision was associated with a perception of greater benefit from receipt of the information (P=0.001). Receivers completing the 2-week (n=76) and 3-month follow-up (n=78) generally reported feeling pleased with the information and having had a more positive experience than distress. However, distress was related to genotype, with those with the s/s allele being most affected.ConclusionsThere was high interest in, and satisfaction with, learning about one's serotonin transporter genotype. Participants appeared to understand that the gene conferred susceptibility to depression rather than a direct causal effect.

scholarly journals Early-onset Alzheimer's disease in Scotland: environmental and familial factors

2001 ◽  
Vol 178 (S40) ◽  
pp. s53-s59 ◽  
Author(s):  
Lawrence J. Whalley
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Environmental Factors ◽  
Disease Model ◽  
Environmental Data ◽  
Paternal Age ◽  
Environment Interaction ◽  
Gene Environment Interaction ◽  
Gene Environment ◽  
Genetic And Environmental Factors

BackgroundAlzheimer's disease (AD) is a common, complex, age-related disorder in which both genetic and environmental factors are important.AimsTo integrate recent studies on genetic and environmental factors in AD into a multi-factorial disease model.MethodDisease models to explain gene-environment interaction in cardiovascular disease are related to observations on AD.ResultsInformative, community-based studies on the genetic epidemiology of AD are rare. Putative risk factors from the Scottish studies include increased paternal age in AD men and coal mining as paternal occupation in both AD and vascular dementia. Migration effects suggest that environmental factors in high-incidence AD areas are important during adult life.ConclusionsThe studies summarised do not provide sufficient data to support a single comprehensive disease model of gene-environment interaction in AD. Future studies will require very large (≥600) sample sizes, molecular genetic analysis, and environmental data that span neurodevelopment and the period between disease onset and appearance of clinical symptoms.

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