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1.
Clin Epidemiol ; 15: 785-794, 2023.
Article in English | MEDLINE | ID: mdl-37396023

ABSTRACT

Purpose: To study the agreement on disease prevalence between survey data and national health register data among people aged over 90. Patients and Methods: The survey data were from the Vitality 90+ Study conducted among 1637 community dwellers and persons in long-term care aged 90 and over in Tampere, Finland. The survey was linked with two national health registers, including hospital discharge data and prescription information. The prevalence of 10 age-related chronic diseases was calculated for each data source and the agreement between the survey and the registers was estimated using Cohen's kappa statistics and positive and negative percent agreement. Results: The prevalence of most diseases was higher in the survey than in the registers. The level of agreement was highest when the survey was compared with information combined from both registers. Agreement was almost perfect for Parkinson's disease (ĸ=0.81) and substantial for diabetes (ĸ=0.75) and dementia (ĸ=0.66). For heart disease, hypertension, stroke, cancer, osteoarthritis, depression, and hip fracture, the agreement ranged from fair to moderate. Conclusion: Self-reported information on chronic diseases shows acceptable agreement with health register data to warrant the use of survey methods in population-based health studies among the oldest old. It is important to acknowledge the gaps in health registers when validating self-reported information against register data.

2.
BMC Geriatr ; 23(1): 276, 2023 05 06.
Article in English | MEDLINE | ID: mdl-37149593

ABSTRACT

BACKGROUND: The burden of dementia, multimorbidity, and disability is high in the oldest old. However, the contribution of dementia and comorbidities to functional ability in this age group remains unclear. We examined the combined effects of dementia and comorbidities on ADL and mobility disability and differences between dementia-related disability between 2001, 2010, and 2018. METHODS: Our data came from three repeated cross-sectional surveys in the population aged 90 + in the Finnish Vitality 90 + Study. The associations of dementia with disability and the combined effects of dementia and comorbidity on disability adjusted for age, gender, occupational class, number of chronic conditions, and study year were determined by generalized estimating equations. An interaction term was calculated to assess differences in the effects of dementia on disability over time. RESULTS: In people with dementia, the odds of ADL disability were almost five-fold compared to people with three other diseases but no dementia. Among those with dementia, comorbidities did not increase ADL disability but did increase mobility disability. Differences in disability between people with and without dementia were greater in 2010 and 2018 than in 2001. CONCLUSION: We found a widening gap in disability between people with and without dementia over time as functional ability improved mainly in people without dementia. Dementia was the main driver of disability and among those with dementia, comorbidities were associated with mobility disability but not with ADL disability. These results imply the need for strategies to maintain functioning and for clinical updates, rehabilitative services, care planning, and capacity building among care providers.


Subject(s)
Disabled Persons , Aged, 80 and over , Humans , Cross-Sectional Studies , Comorbidity , Activities of Daily Living , Chronic Disease
3.
BMJ Open ; 13(2): e068509, 2023 02 07.
Article in English | MEDLINE | ID: mdl-36750290

ABSTRACT

PURPOSE: Vitality 90+ is an ongoing population-based study with repeated cross-sectional data collections. The study was designed to examine trends in health, functioning, living conditions, quality of life and care needs among the oldest old in Finland. PARTICIPANTS: Nine mailed surveys have been conducted in the city of Tampere between 1995 and 2018. The first three surveys in 1995, 1996 and 1998 included all community-dwelling individuals aged 90 years or older; and the following six surveys in 2001, 2003, 2007, 2010, 2014 and 2018 covered all individuals in Tampere regardless of their living arrangements. In total, the surveys have included 5935 participants (8840 observations). Around 80% of the participants have been women. The participants' age range has been between 90 and 107 years. FINDINGS TO DATE: The surveys have consistently asked the same questions over time, covering basic sociodemographic factors, morbidity, functioning, self-rated health (SRH), living arrangements, social relations, quality of life, care needs and providers of care. Survey data have been linked with national register data on health and social service use, mortality and medication. The main findings regarding the time trends show an increase in the proportion of people independent in activities of daily living and mobility. Along with improved functioning, the number of chronic conditions has increased, and SRH has shown a tendency to decline. In addition, we have found increasing occupational class inequalities in functioning and SRH over time. FUTURE PLANS: The next round of data collection will be completed by the end of 2022. The Vitality 90+ Study welcomes research collaborations that fall within the general aims of the project. The research data 1995-2014 are archived at the Finnish Social Science Data Archive and the data for years 2018 and 2022 will be archived in 2023.


Subject(s)
Activities of Daily Living , Quality of Life , Aged, 80 and over , Humans , Female , Cohort Studies , Finland , Social Conditions , Cross-Sectional Studies
4.
Aging Clin Exp Res ; 35(3): 677-688, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36583848

ABSTRACT

BACKGROUND: There are a very few studies focusing on the individual-based survival with a long follow-up time. AIM: To identify predictors and determine their joint predictive value for longevity using individual-based outcome measures. METHODS: Data were drawn from Tampere Longitudinal Study on Aging (TamELSA), a study of individuals' age 60-89 years (N = 1450) with a mortality follow-up of up to 35 years. Two measures of longevity were used: the longevity difference (LD) and realized probability of dying (RPD), both of which compare each individual's longevity with their life expectancy as derived from population life tables. Independent variables were categorized into five domains: sociodemographic, health and functioning, subjective experiences, social activities, and living conditions. Linear regression models were used in three steps: bivariate analysis for each variable, multivariate analysis based on backward elimination for each domain, and one final model. RESULTS: The most important predictors of both outcomes were marital status, years smoked regularly, mobility, self-rated health, endocrine and metabolic diseases, respiratory diseases, and unwillingness to do things or lack of energy. The explained variance in longevity was 13.8% for LD and 14.1% for RPD. This demonstrated a large proportion of unexplained error margins for the prediction of individual longevity, even though many known predictors were used. DISCUSSION AND CONCLUSIONS: Several predictors associated with longer life were found. Yet, on an individual level, it remains difficult to predict who will live longer than their age peers. The stochastic element in the process of aging and in death may affect this prediction.


Subject(s)
Aging , Longevity , Humans , Aged , Aged, 80 and over , Longitudinal Studies , Life Expectancy , Probability
5.
J Aging Health ; 35(5-6): 370-382, 2023 06.
Article in English | MEDLINE | ID: mdl-36256914

ABSTRACT

OBJECTIVES: To examine trends in the prevalence of dementia and related comorbidities among the oldest old. METHODS: Six repeated cross-sectional surveys were conducted between 2001 and 2018, each including all inhabitants aged over 90 in Tampere, Finland (n = 5386). Co-occurring conditions and their time trends among participants with dementia were examined using logistic regression and generalized estimating equations. RESULTS: The prevalence of dementia decreased from 47% in 2007 to 41% in 2018. Throughout the study period, depression was more common among people with dementia compared to those without. The prevalence of hypertension, diabetes, and osteoarthritis increased and the prevalence of depression decreased among people with dementia. The mean number of comorbidities increased from 2.0 in 2001 to 2.3 in 2018. DISCUSSION: Dementia remains highly prevalent among the oldest old and it is accompanied by an increasing burden of comorbidities, posing a challenge to people with dementia, their caregivers, and care systems.


Subject(s)
Dementia , Hypertension , Aged, 80 and over , Humans , Dementia/epidemiology , Finland/epidemiology , Cross-Sectional Studies , Comorbidity , Hypertension/epidemiology , Prevalence
6.
Geroscience ; 45(1): 85-103, 2023 02.
Article in English | MEDLINE | ID: mdl-35864375

ABSTRACT

Circulating cell-free DNA (cf-DNA) has emerged as a promising biomarker of ageing, tissue damage and cellular stress. However, less is known about health behaviours, ageing phenotypes and metabolic processes that lead to elevated cf-DNA levels. We sought to analyse the relationship of circulating cf-DNA level to age, sex, smoking, physical activity, vegetable consumption, ageing phenotypes (physical functioning, the number of diseases, frailty) and an extensive panel of biomarkers including blood and urine metabolites and inflammatory markers in three human cohorts (N = 5385; 17-82 years). The relationships were assessed using correlation statistics, and linear and penalised regressions (the Lasso), also stratified by sex.cf-DNA levels were significantly higher in men than in women, and especially in middle-aged men and women who smoke, and in older more frail individuals. Correlation statistics of biomarker data showed that cf-DNA level was higher with elevated inflammation (C-reactive protein, interleukin-6), and higher levels of homocysteine, and proportion of red blood cells and lower levels of ascorbic acid. Inflammation (C-reactive protein, glycoprotein acetylation), amino acids (isoleucine, leucine, tyrosine), and ketogenesis (3-hydroxybutyrate) were included in the cf-DNA level-related biomarker profiles in at least two of the cohorts.In conclusion, circulating cf-DNA level is different by sex, and related to health behaviour, health decline and metabolic processes common in health and disease. These results can inform future studies where epidemiological and biological pathways of cf-DNA are to be analysed in details, and for studies evaluating cf-DNA as a potential clinical marker.


Subject(s)
C-Reactive Protein , Cell-Free Nucleic Acids , Male , Humans , Female , Middle Aged , Aged , Aging/genetics , Biomarkers , Phenotype , Inflammation , Health Behavior , DNA
8.
Eur J Ageing ; 19(2): 161-173, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35663915

ABSTRACT

Overall progress in life expectancy (LE) depends increasingly on survival in older ages. The birth cohorts now reaching old age have experienced considerable educational expansion, which is a driving force for the social change and social inequality. Thus, this study examines changes in old age LE by educational attainment in the Nordic countries and aims to find out to what extent the change in national LEs is attributable to education-specific mortality and the shifting educational composition. We used national register data comprising total 65 + populations in Denmark, Finland, Norway and Sweden to create period life tables stratified by five-year age groups (65-90 +), sex and educational attainment. Difference in LE between 2001 and 2015 was decomposed into the contributions of mortality changes within each educational group and changes in educational composition. Increasing LE at all ages and in all educational groups coincided with persistent and growing educational inequalities in all countries. Most of the gains in LE at age 65 could be attributed to decreased mortality (63-90%), especially among those with low education, the largest educational group in most countries. The proportion of the increase in LE attributable to improved education was 10-37%, with the highest contributions recorded for women in Norway and Sweden. The rising educational levels in the Nordic countries still carry potential for further gains in national LEs. However, the educational expansion has contributed to uneven gains in LE between education groups, which poses a risk for the future increase of inequalities in LE. Supplementary Information: The online version contains supplementary material available at 10.1007/s10433-022-00698-y.

9.
Eur J Ageing ; 19(2): 155-159, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35578718
10.
Health Soc Care Community ; 30(5): e2571-e2579, 2022 09.
Article in English | MEDLINE | ID: mdl-34970804

ABSTRACT

Family members are important providers of care for older people. In residential long-term care, however, their role is not always simple and straightforward: responsibility for care provision rests officially with staff members, but in practice family members often contribute to providing care. The main reason for admission to long-term care is functional decline. At the same time, the maintenance of functional ability is a central goal in long-term care. It is therefore reasonable to assume that functional ability is also an important factor in the relationship between family members and long-term care residents. This study aims to explore how family members experience their role in supporting the functional ability of older relatives in residential long-term care. With the approval of the local hospital district's ethics committee, we conducted semi-structured interviews with family members (n = 16) in Finland in 2016. Thematic data analysis showed that family members supported the functional ability of their older parent or spouse by organising and monitoring care and by bringing forth their relative's personal needs and wishes. They often saw their role alongside staff members as ambiguous, and their understanding of the scope of support for functioning extended beyond physical everyday tasks. In their talk, family members broadened the concept of functional ability from daily chores and independence to meaningful social relations and acknowledgement of person's individual background and preferences. Family members' views offer valuable insights into residents' personal needs, values and preferences and in doing so help care workers to support their functional ability with a person-centred care approach.


Subject(s)
Homes for the Aged , Nursing Homes , Aged , Family , Finland , Humans , Long-Term Care , Qualitative Research
11.
Aging Clin Exp Res ; 33(12): 3285-3292, 2021 Dec.
Article in English | MEDLINE | ID: mdl-33939125

ABSTRACT

BACKGROUND: Comorbidities have major implications for the care of people with dementia. AIM: To investigate the patterns of comorbidities in dementia in the last five years of life and how these patterns differed between three cohorts. METHODS: The study included people who died at age 70 and above in 2001 (n = 13,717), 2007 (n = 34,750) and 2013 (n = 38,087) in Finland. ICD-10 morbidity data for a five-year period prior to death were extracted from national registers. Principal component analysis was employed to identify patterns for several morbidities. The associations of principal component scores with dementia were analysed using binary logistic regression. Linear regression was used to examine changes in the number of morbidities in patterns over time. RESULTS: The morbidity patterns identified in the last years of life were (1) cardiometabolic disorders, (2) neurological, (3) cerebrovascular diseases and (4) musculoskeletal, thyroid and psychiatric disorders. Among the patterns, neurological and musculoskeletal, thyroid and psychiatric disorders were associated with dementia. The number of diagnoses in the cerebrovascular pattern increased and those in the musculoskeletal, thyroid and psychiatric pattern decreased over time. DISCUSSION: Comorbidity patterns identified in this nationwide register study are largely in line with previous evidence. Time difference in these patterns provide crucial information for service planning. CONCLUSIONS: Comorbidities in dementia in the last years of life occur in patterns and change over time. More systematic monitoring and updated clinical guidelines are needed for the care of comorbidities with dementia.


Subject(s)
Dementia , Aged , Comorbidity , Dementia/epidemiology , Finland/epidemiology , Humans
13.
Exp Gerontol ; 143: 111119, 2021 01.
Article in English | MEDLINE | ID: mdl-33086079

ABSTRACT

Plasma contains several bioactive molecules (RNA, DNA, proteins, lipids, and metabolites), which are well preserved in extracellular vesicles, that are involved in many types of cell-to-cell interactions, and are capable of modifying biological processes in recipient cells. To obtain information about the source of mRNA molecules present in the plasma, we analyzed the plasma extracellular RNA (exRNA) of healthy individuals using RNA-sequencing and compared it to that of the peripheral blood mononuclear cell (PBMCs) of the same individual. The resultant data indicates that large proportion of the transcripts in plasma are derived from cell types other than PBMCs. To assess aging-associated changes in the plasma exRNA composition, gene ontology enrichment analysis was performed, revealing a functional decline in biological processes as a result of aging. Additionally, plasma RNA levels were analyzed with differential expression analysis, revealing 10 transcripts with significant aging-associated changes. Thus, it seems that the plasma exRNA is not fully derived from the PBMCs. Instead, other cell types supply RNAs to constitute the plasma exRNA compartment. This was true in both the young and elderly individuals that were tested. Furthermore, the RNA content of the plasma showed significant changes due to aging, affecting important biological processes.


Subject(s)
Leukocytes, Mononuclear , Transcriptome , Aged , Aging/genetics , Humans , RNA/genetics , Sequence Analysis, RNA
14.
J Gerontol A Biol Sci Med Sci ; 76(7): 1227-1233, 2021 06 14.
Article in English | MEDLINE | ID: mdl-32506117

ABSTRACT

BACKGROUND: It remains unclear whether increasing longevity is accompanied by a compression or expansion of poor health and disability. We examined trends of physical functioning and morbidity in a population aged 90 and older, and disease- and disability-free life expectancy (LE) at age 90 between 2001 and 2018 in Finland's third most populated city. METHODS: We used survey data from the Vitality 90+ Study, which comprises a series of six repeated mailed surveys (7,590 observations). Information on mortality came from Statistics Finland. We examined trends of functioning (activities of daily living [ADL] and mobility) and cardiovascular and dementia morbidity using age-adjusted generalized estimating equation models stratified by sex. In addition, age-, sex-, and period-specific health expectancies were calculated using Sullivan's method. RESULTS: Over time, functioning improved, especially, in women, and morbidity increased in men. From 2001 to 2018, LE at age 90 increased by 5.3 months for men and 6.4 months for women. LE without ADL disability increased by 5.0 months for men and 8.4 months for women, and LE without mobility disability by 6.0 months for men and 4.4 months for women. LE without cardiovascular and dementia morbidity decreased for men (2.6 months) and increased for women (1.9 months). CONCLUSIONS: In relative terms, we found a compression of disability for both sexes and an expansion of morbidity for men. Although the trends overall are rather positive, the increase in absolute morbidity and, to some extent, in disability will inevitably mean increasing care needs with population aging.


Subject(s)
Life Expectancy/trends , Morbidity/trends , Physical Functional Performance , Activities of Daily Living , Aged, 80 and over , Cardiovascular Diseases/epidemiology , Cross-Sectional Studies , Dementia/epidemiology , Female , Finland/epidemiology , Humans , Male , Mobility Limitation , Surveys and Questionnaires
15.
Eur J Ageing ; 17(3): 361-369, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32904873

ABSTRACT

While it is known that those who are living their last years are frequent users of social and health services, research about medicines at the end of life is scarce. We examined whether the proportions of purchasers and the types of prescription medicines purchased during a 2-year period differed between community-dwelling old people who died (decedents) in 2002, 2006 or 2011 and old people who lived at least 2 years longer (survivors) in Finland. We also examined how those differences changed over time. The study population was identified from nationwide registers and consisted of 174,097 community-dwelling people who were 70 years of age or older. Of these, 81,893 were decedents and 92,204 survivors. Data on purchases of medicines were gathered from the Finnish prescription database. Along with descriptive analyses, binary logistic regression analysis was used to find the association between decedent status and the purchase of medicines in general and different categories of medicines in particular. Almost all community-dwelling decedents and survivors purchased medicines at least once during the 2-year period. Over time, the proportion of purchasers increased in both groups but especially among survivors, thereby reducing the differences between the groups. However, the probability of purchasing medicines in general and different categories of medicine in particular remained significantly higher for decedents than for survivors after adjustments. This study shows that purchases of medication are concentrated at the end of life, as is the use of social and health services. However, the differences between decedents and survivors diminish over time.

16.
Eur J Ageing ; 17(2): 207-216, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32547348

ABSTRACT

Longitudinal studies examining changes in physical functioning with advancing age among very old people are plagued by high death rates, which can lead to biased estimates. This study was conducted to analyse changes in physical functioning among the oldest old with three distinct methods which differ in how they handle dropout due to death. The sample consisted of 3992 persons aged 90 or over in the Vitality 90+ Study who were followed up on average for 2.5 years (range 0-13 years). A generalized estimating equation (GEE) with independent 'working' correlation, a linear mixed-effects (LME) model and a joint model consisting of longitudinal and survival submodels were used to estimate the effect of age on physical functioning over 13 years of follow-up. We observed significant age-related decline in physical functioning, which furthermore accelerated significantly with age. The average rate of decline differed markedly between the models: the GEE-based estimate for linear decline among survivors was about one-third of the average individual decline in the joint model and half the decline indicated by the LME model. In conclusion, the three methods yield substantially different views on decline in physical functioning: the GEE model may be useful for considering the effect of intervention measures on the outcome among living people, whereas the LME model is biased regarding studying outcomes associated with death. The joint model may be valuable for predicting the future characteristics of the oldest old and planning elderly care as life expectancy continues gradually to rise.

17.
Immun Ageing ; 17: 11, 2020.
Article in English | MEDLINE | ID: mdl-32435269

ABSTRACT

BACKGROUND: The human genome contains remnants of ancient retroviral infections called human endogenous retroviruses (HERV). Their expression is often observed in several diseases of autoimmune or inflammatory nature. However, the exact biological mechanisms induced by HERVs are still poorly understood. We have previously shown that several HERVs of the HERV-K (HML-2) family are strongly transcribed in the peripheral blood mononuclear cells (PBMC) derived from young and old individuals. To examine the potential functional consequences of HERV-K (HML-2) expression, we have now analyzed the correlation of its expression with age-associated changes in the transcriptome using gene set enrichment analysis (GSEA). We focused our analysis on the HERV-K (HML-2) provirus at 1q22, also known as ERVK-7. RESULTS: The genes strongly correlating with the expression of HERV-K (HML-2) provirus at 1q22 expression were found to be almost entirely different in young and old individuals. The number of genes strongly correlating (Pearson correlation coefficient ≥ 0.7) with 1q22 expression was 946 genes in the old and 435 in the young, of which only 41 genes correlated strongly in both. Consequently, the related gene ontology (GO) biological processes were different. In the older individuals, many of the highest correlating processes relate to the function of neutrophils. CONCLUSIONS: The results of this work suggest that the biological processes associated with the expression of HERV-K (HML-2) provirus at 1q22 are different in the blood of young and old individuals. Specifically, a strong association was found in the older individuals between neutrophil activity and the expression of the HERV-K (HML-2) provirus at 1q22. These findings offer insight into potential effects of altered HERV expression in older individuals.

18.
SSM Popul Health ; 11: 100567, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32258355

ABSTRACT

No previous study has explored the structure of self-rated health (SRH), a measure holding strong predictive value for future health events, in the oldest old or in individuals with dementia. The aim was to construct a structural equation model of SRH for oldest old in general and for oldest old with dementia, and to explore direct and indirect associations between health-related factors and SRH. Cross-sectional data from the Vitality 90+, a population-based study in the city of Tampere, Finland, was used. Data were gathered by a mailed questionnaire in 2014. Altogether 1299 nonagenarians, of which 408 had self-reported dementia or cognitive decline, were included. Structural equation models were constructed for all participants and separately for participants with dementia. Diseases (heart disease, stroke, diabetes, arthritis, hip fracture, cancer and dementia for the model for all), dizziness, hearing, vision, mobility, activities of daily living, fatigue, depression and SRH were included in the models. Among all participants, fatigue, depression, problems in mobility, dizziness, deficits in vision and heart disease were directly associated with poor SRH. Among participants with dementia, only fatigue, dizziness and deficits in vision were directly associated with poor SRH. Among all participants, dementia and arthritis were indirectly associated with poor SRH through problems in mobility, depression and fatigue. Among the oldest old, the effects of diseases on SRH were mainly manifested through the consequences of diseases, namely fatigue, dizziness, deficits in vision and problems in mobility. Depression has an important direct and indirect role, and dementia and arthritis an important indirect role in the structure of SRH. Dementia weakens many of the direct and indirect associations for SRH.

19.
Gerontol Geriatr Med ; 5: 2333721419870629, 2019.
Article in English | MEDLINE | ID: mdl-31489341

ABSTRACT

Welfare states increasingly rely on aging in place policies and have cut back on institutional long-term care (LTC) provision. Simultaneously, the major determinants of LTC use, that is, dementia and living to very old age, are increasing. We investigated how increasing longevity and concomitant dementia were associated with changes in round-the-clock LTC use in the last 5 years of life between 1996 and 2013. Retrospective data drawn from national registers included all those who died aged 70+ in 2007 and 2013, plus a 40% random sample from 2001 (N = 86,554). A generalized estimating equations (GEE) were used to estimate the association of dementia and age with LTC use during three study periods 1996-2001, 2002-2007, and 2008-2013. Between the study periods, the total number of days spent in LTC increased by around 2 months. Higher ages at death and the increased number of persons with dementia contributed to this increase. The group of the most frequent LTC users, that is, people aged 90+ with or without dementia, grew the most in size, yet their LTC use decreased. The implications of very old age and concomitant dementia for care needs must be acknowledged to guarantee an adequate quantity and quality of care.

20.
Nat Commun ; 10(1): 3669, 2019 08 14.
Article in English | MEDLINE | ID: mdl-31413261

ABSTRACT

Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity.


Subject(s)
Apolipoprotein E2/genetics , Apolipoprotein E4/genetics , Heat-Shock Proteins/genetics , Longevity/genetics , Endoplasmic Reticulum Chaperone BiP , Genome-Wide Association Study , Humans
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