Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
31469771
TITLE
Neuroticism as a predictor of frailty in old age: a genetically informative approach.
ABSTRACT
OBJECTIVE NlmCategory: OBJECTIVE
Neuroticism is associated with poor health outcomes, but its contribution to the accumulation of health deficits in old age, i.e. the frailty index, is largely unknown. We aimed to explore associations between neuroticism and frailty cross-sectionally and longitudinally, and to investigate the contribution of shared genetic influences.
METHOD NlmCategory: METHODS
Neuroticism is associated with poor health outcomes, but its contribution to the accumulation of health deficits in old age, i.e. the frailty index, is largely unknown. We aimed to explore associations between neuroticism and frailty cross-sectionally and longitudinally, and to investigate the contribution of shared genetic influences. Data were derived from the UK Biobank (UKB, n=274,951), the Australian Over 50's Study (AO50, n=2,849) and the Swedish Twin Registry (SALT n=18,960, SATSA n=1,365). Associations between neuroticism and the frailty index were investigated using regression analysis cross-sectionally in UKB, AO50 and SATSA, and longitudinally in SALT (25-29y follow-up) and SATSA (6 and 23y follow-up). The co-twin control method was applied to explore the contribution of underlying shared familial factors (SALT, SATSA, AO50). Genome-wide polygenic risk scores for neuroticism were used in all samples to further assess whether common genetic variants associated with neuroticism predict frailty.
RESULTS NlmCategory: RESULTS
Neuroticism is associated with poor health outcomes, but its contribution to the accumulation of health deficits in old age, i.e. the frailty index, is largely unknown. We aimed to explore associations between neuroticism and frailty cross-sectionally and longitudinally, and to investigate the contribution of shared genetic influences. Data were derived from the UK Biobank (UKB, n=274,951), the Australian Over 50's Study (AO50, n=2,849) and the Swedish Twin Registry (SALT n=18,960, SATSA n=1,365). Associations between neuroticism and the frailty index were investigated using regression analysis cross-sectionally in UKB, AO50 and SATSA, and longitudinally in SALT (25-29y follow-up) and SATSA (6 and 23y follow-up). The co-twin control method was applied to explore the contribution of underlying shared familial factors (SALT, SATSA, AO50). Genome-wide polygenic risk scores for neuroticism were used in all samples to further assess whether common genetic variants associated with neuroticism predict frailty. High neuroticism was consistently associated with greater frailty cross-sectionally (adjusted β [95% confidence intervals] in UKB=0.32[0.32-0.33]; AO50=0.35[0.31-0.39]; SATSA=0.33[0.27-0.39]) and longitudinally up to 29 years (SALT=0.24[0.22-0.25]; SATSA 6y=0.31[0.24-0.38]; SATSA 23y=0.16[0.07-0.25]). When adjusting for underlying shared genetic and environmental factors the neuroticism-frailty association remained significant, although decreased. Polygenic risk scores for neuroticism significantly predicted frailty in the two larger samples (meta-analyzed total β=0.059[0.055-0.062]).
CONCLUSION NlmCategory: CONCLUSIONS
Neuroticism is associated with poor health outcomes, but its contribution to the accumulation of health deficits in old age, i.e. the frailty index, is largely unknown. We aimed to explore associations between neuroticism and frailty cross-sectionally and longitudinally, and to investigate the contribution of shared genetic influences. Data were derived from the UK Biobank (UKB, n=274,951), the Australian Over 50's Study (AO50, n=2,849) and the Swedish Twin Registry (SALT n=18,960, SATSA n=1,365). Associations between neuroticism and the frailty index were investigated using regression analysis cross-sectionally in UKB, AO50 and SATSA, and longitudinally in SALT (25-29y follow-up) and SATSA (6 and 23y follow-up). The co-twin control method was applied to explore the contribution of underlying shared familial factors (SALT, SATSA, AO50). Genome-wide polygenic risk scores for neuroticism were used in all samples to further assess whether common genetic variants associated with neuroticism predict frailty. High neuroticism was consistently associated with greater frailty cross-sectionally (adjusted β [95% confidence intervals] in UKB=0.32[0.32-0.33]; AO50=0.35[0.31-0.39]; SATSA=0.33[0.27-0.39]) and longitudinally up to 29 years (SALT=0.24[0.22-0.25]; SATSA 6y=0.31[0.24-0.38]; SATSA 23y=0.16[0.07-0.25]). When adjusting for underlying shared genetic and environmental factors the neuroticism-frailty association remained significant, although decreased. Polygenic risk scores for neuroticism significantly predicted frailty in the two larger samples (meta-analyzed total β=0.059[0.055-0.062]). Neuroticism in mid-life predicts frailty in late-life. Neuroticism may have a causal influence on frailty, whereas both environmental and genetic influences, including neuroticism-associated common genetic variants, contribute to this relationship.
DATE PUBLISHED
2019 Aug 28
HISTORY
PUBSTATUS PUBSTATUSDATE
entrez 2019/08/31 06:00
pubmed 2019/08/31 06:00
medline 2019/08/31 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Danielsdottir HB Danielsdottir Hilda Bjork HB Department of Medical Epidemiology & Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Jylhävä J Jylhävä Juulia J Department of Medical Epidemiology & Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Hägg S Hägg Sara S Department of Medical Epidemiology & Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Lu Y Lu Yi Y Department of Medical Epidemiology & Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Colodro-Conde L Colodro-Conde Lucía L Department of Genetics and Computational Biology. QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Martin NG Martin Nicholas G NG Department of Genetics and Computational Biology. QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Pedersen NL Pedersen Nancy L NL Department of Medical Epidemiology & Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Mosing MA Mosing Miriam A MA Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Lehto K Lehto Kelli K Department of Chronic Diseases, Institute for Health Development, Tallinn, Estonia.
INVESTIGATORS
JOURNAL
VOLUME:
ISSUE:
TITLE: Psychosomatic medicine
ISOABBREVIATION: Psychosom Med
YEAR: 2019
MONTH: Aug
DAY: 28
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1534-7796
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Psychosom Med
COUNTRY: United States
ISSNLINKING: 0033-3174
NLMUNIQUEID: 0376505
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
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