Journal ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association · December 1, 2024
BACKGROUND: The Alzheimer's Association reports that more than two-thirds of the approximately 5 million Alzheimer's disease (AD) cases in the USA are women. With studies suggesting a high genetic heritability for AD, gaining a better understanding of the ...
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Journal ArticleInternational journal of molecular sciences · November 2024
Physical activity (PA) is a modifiable factor in mitigating/preventing Alzheimer's disease (AD). It is crucial to identify the conditions under which PA's effects on AD risk would be beneficial. This study aims to gain insights into pleiotropic predisposit ...
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Journal ArticleAlzheimer's & dementia (Amsterdam, Netherlands) · April 2024
IntroductionThe variability in apolipoprotein E (APOE) ε4-attributed susceptibility to Alzheimer's disease (AD) across ancestries, sexes, and ages may stem from the modulating effects of other genetic variants.MethodsWe exam ...
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Journal ArticleGenes · September 2023
Alzheimer's disease (AD) and cardiovascular traits might share underlying causes. We sought to identify clusters of cardiovascular traits that share genetic factors with AD. We conducted a univariate exome-wide association study and pair-wise pleiotropic a ...
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Journal ArticleGeroScience · February 2023
The mechanisms of incomplete penetrance of risk-modifying impacts of apolipoprotein E (APOE) ε2 and ε4 alleles on Alzheimer's disease (AD) have not been fully understood. We performed genome-wide analysis of differences in linkage disequilibrium (LD) patte ...
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Journal ArticleJournal of Alzheimer's disease : JAD · January 2023
BackgroundThe lack of efficient preventive interventions against Alzheimer's disease (AD) calls for identifying efficient modifiable risk factors for AD. As diabetes shares many pathological processes with AD, including accumulation of amyloid pla ...
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Journal ArticleAging cell · December 2022
Age-related diseases characteristic of post-reproductive life, aging, and life span are the examples of polygenic non-Mendelian traits with intricate genetic architectures. Polygenicity of these traits implies that multiple variants can impact their risks ...
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Journal ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association · November 2022
IntroductionThe apolipoprotein E (APOE) ε2 and ε4 alleles have beneficial and adverse impacts on Alzheimer's disease (AD), respectively, with incomplete penetrance, which may be modulated by other genetic variants.MethodsWe examined wheth ...
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Journal ArticleAging · November 2022
Capturing the genetic architecture of Alzheimer's disease (AD) is challenging because of the complex interplay of genetic and non-genetic factors in its etiology. It has been suggested that AD biomarkers may improve the characterization of AD pathology and ...
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Journal ArticleNeurobiology of aging · February 2022
Despite advances, the roles of genetic variants from the APOE-harboring 19q13.32 region in Alzheimer's disease (AD) remain controversial. We leverage a comprehensive approach to gain insights into a more homogeneous genetic architecture of AD in this regio ...
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Journal ArticleGeroScience · February 2022
Epidemiological studies report beneficial associations of higher educational attainment (EDU) with Alzheimer's disease (AD). Prior genome-wide association studies (GWAS) also reported variants associated with AD and EDU separately. The analysis of pleiotro ...
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Journal ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association · December 1, 2021
BACKGROUND: The APOE gene harboring the ε2 and ε4 alleles encoded by minor alleles of rs7412 and rs429358 single nucleotide polymorphisms (SNPs), respectively, is one of the most studied genes in humans. Despite that, the problem of whether the association ...
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Journal ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association · November 2021
IntroductionDespite advances, understanding the protective role of the apolipoprotein E (APOE) ε2 allele in Alzheimer's disease (AD) remains elusive.MethodsWe examined associations of variants comprised of the TOMM40 rs8106922 and APOE rs ...
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Journal ArticleGeroScience · December 2020
Polygenic risk scores (PRSs) discriminate trait risks better than single genetic markers because they aggregate the effects of risk alleles from multiple genetic loci. Constructing pleiotropic PRSs and understanding heterogeneity, and the replication of PR ...
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Journal ArticleThe journals of gerontology. Series A, Biological sciences and medical sciences · September 2020
Prevailing strategies in genome-wide association studies (GWAS) mostly rely on principles of medical genetics emphasizing one gene, one function, one phenotype concept. Here, we performed GWAS of blood lipids leveraging a new systemic concept emphasizing c ...
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Journal ArticleNeurobiology of aging · March 2020
The role of even the strongest genetic risk factor for Alzheimer's disease (AD), the apolipoprotein E (APOE) ε4 allele, in its etiology remains poorly understood. We examined molecular signatures of AD defined as differences in linkage disequilibrium patte ...
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Journal ArticleAlzheimer's & dementia (Amsterdam, Netherlands) · January 2020
IntroductionApolipoprotein E (APOE) ε2 and ε4 alleles encoded by rs7412 and rs429358 polymorphisms, respectively, are landmark contra and pro "risk" factors for Alzheimer's disease (AD).MethodsWe examined differences in linkage dis ...
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Journal ArticleAlzheimer's & dementia (Amsterdam, Netherlands) · January 2020
IntroductionAs a multifactorial polygenic disorder, Alzheimer's disease (AD) can be associated with complex haplotypes or compound genotypes.MethodsWe examined associations of 4960 single nucleotide polymorphism (SNP) triples, comprising ...
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Journal ArticleGeroScience · December 2019
Late life disability is a highly devastating condition affecting 20% or more of persons aged 65 years and older in the USA; it is an important determinant of acute medical and long-term care costs which represent a growing burden on national economies. Dis ...
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Journal ArticleAging cell · February 2019
The TOMM40-APOE variants are known for their strong, antagonistic associations with Alzheimer's disease and body weight. While a stronger role of the APOE than TOMM40 variants in Alzheimer's disease was suggested, comparative contribution of the TOMM40-APO ...
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Journal ArticleFrontiers in genetics · January 2019
Age-related phenotypes are characterized by genetic heterogeneity attributed to an uncertain role of evolution in establishing their molecular mechanisms. Here, we performed univariate and pleiotropic meta-analyses of 24 age-related phenotypes dealing with ...
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Journal ArticleAging cell · August 2018
Although the APOE region is the strongest genetic risk factor for Alzheimer's diseases (ADs), its pathogenic role remains poorly understood. Elucidating genetic predisposition to ADs, a subset of age-related diseases characteristic for postreproductive per ...
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Journal ArticleExperimental gerontology · July 2018
BackgroundsElucidating the causal effects of common intermediate risk factors on the onset of age-related diseases is indispensable for developing prevention and intervention procedures.MethodsWe conducted two-stage time-to-event Mendelia ...
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Journal ArticleExperimental gerontology · July 2018
Despite evident success in clarifying many important features of Alzheimer's disease (AD) the efficient methods of its prevention and treatment are not yet available. The reasons are likely to be the fact that AD is a multifactorial and heterogeneous healt ...
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Journal ArticleAging · March 2018
A conceptual difficulty in genetics of age-related phenotypes that make individuals vulnerable to disease in post-reproductive life is genetic heterogeneity attributed to an undefined role of evolution in establishing their molecular mechanisms. Here, we p ...
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Journal ArticleAging cell · February 2017
Traditionally, genomewide association studies (GWAS) have emphasized the benefits of large samples in the analyses of age-related traits rather than their specific properties. We adopted a realistic concept of genetic susceptibility to inherently heterogen ...
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Journal ArticleBiogerontology · November 2016
The apolipoprotein E (apoE) is a classic example of a gene exhibiting pleiotropism. We examine potential pleiotropic associations of the apoE2 allele in three biodemographic cohorts of long-living individuals, offspring, and spouses from the Long Life Fami ...
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Journal ArticlePLoS genetics · November 2016
Gaining insights into genetic predisposition to age-related diseases and lifespan is a challenging task complicated by the elusive role of evolution in these phenotypes. To gain more insights, we combined methods of genome-wide and candidate-gene studies. ...
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Journal ArticleScientific reports · October 2016
Common strategy of genome-wide association studies (GWAS) relying on large samples faces difficulties, which raise concerns that GWAS have exhausted their potential, particularly for complex traits. Here, we examine the efficiency of the traditional sample ...
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Journal ArticleBiogerontology · February 2016
Increasing proportions of elderly individuals in developed countries combined with substantial increases in related medical expenditures make the improvement of the health of the elderly a high priority today. If the process of aging by individuals is a ma ...
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Journal ArticleNorth American actuarial journal : NAAJ · January 2016
Background and objectiveTo clarify mechanisms of genetic regulation of human aging and longevity traits, a number of genome-wide association studies (GWAS) of these traits have been performed. However, the results of these analyses did not meet ex ...
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Journal ArticleFrontiers in genetics · January 2016
Age-related diseases may result from shared biological mechanisms in intrinsic processes of aging. Genetic effects on age-related diseases are often modulated by environmental factors due to their little contribution to fitness or are mediated through cert ...
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Journal ArticleFrontiers in genetics · January 2016
This paper shows that the effects of causal SNPs on lifespan, estimated through GWAS, may be confounded and the genetic structure of the study population may be responsible for this effect. Simulation experiments show that levels of linkage disequilibrium ...
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Chapter · January 1, 2016
Age is a major risk factor for phenotypes characterizing human health, well-being, and survival in late life. The risks of these phenotypes expressed in forms of pathological dysregulation of physiological functions, incidence or prevalence of diseases, ca ...
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Chapter · January 1, 2016
It is well known from epidemiological research that values of indices describing physiological states at a given age may influence human morbidity and mortality risks. Studies of the connections between aging and life span suggest that the dynamic properti ...
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Chapter · January 1, 2016
Decades of studies of candidate genes show that they are not linked to aging-related traits in a straightforward manner. Recent genome-wide association studies (GWAS) have reached fundamentally the same conclusion by showing that traits in late life are li ...
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Journal ArticleRejuvenation research · April 2015
The lack of evolutionary established mechanisms linking genes to age-related traits makes the problem of genetic susceptibility to health span inherently complex. One complicating factor is genetic trade-off. Here we focused on long-living participants of ...
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Journal ArticleFrontiers in genetics · January 2015
BackgroundThe roles of genetic factors in human longevity would be better understood if one can use more efficient methods in genetic analyses and investigate pleiotropic effects of genetic variants on aging and health related traits.Data and ...
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Journal ArticlePloS one · January 2015
Insights into genetic origin of diseases and related traits could substantially impact strategies for improving human health. The results of genome-wide association studies (GWAS) are often positioned as discoveries of unconditional risk alleles of complex ...
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Journal ArticlePlos Genetics · January 1, 2014
Enduring interest in the Apolipoprotein E (ApoE) polymorphism is ensured by its evolutionary-driven uniqueness in humans and its prominent role in geriatrics and gerontology. We use large samples of longitudinally followed populations from the Framingham H ...
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Journal ArticleAge (Dordrecht, Netherlands) · April 2013
Despite notable progress of the candidate-gene and genome-wide association studies (GWAS), understanding the role of genes contributing to human health and lifespan is still very limited. We use the Framingham Heart Study to elucidate if recognizing the ro ...
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Journal ArticleAge (Dordrecht, Netherlands) · April 2013
Studies focusing on unraveling the genetic origin of health span in humans assume that polygenic, aging-related phenotypes are inherited through Mendelian mechanisms of inheritance of individual genes. We use the Framingham Heart Study (FHS) data to examin ...
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Journal ArticleAging cell · April 2013
The inherent complexity of aging-related traits can temper progress in unraveling the genetic origins of healthspan. We focus on two generations in the Framingham Heart Study, the original (FHS) and offspring (FHSO) cohorts, to determine whether aging-rela ...
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Journal ArticleRejuvenation research · February 2013
Decades of studies of candidate genes show their complex role in aging-related traits. We focus on apolipoprotein E e2/3/4 polymorphism and ages at onset of cardiovascular diseases (CVD) and cancer in the parental and offspring generations of the Framingha ...
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Journal ArticleFrontiers in genetics · January 2013
Background and objectiveThe influence of genes on human lifespan is mediated by biological processes that characterize body's functioning. The age trajectories of these processes contain important information about mechanisms linking aging, health ...
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Journal ArticleAging cell · June 2011
Progress in unraveling the genetic origins of healthy aging is tempered, in part, by a lack of replication of effects, which is often considered a signature of false-positive findings. We convincingly demonstrate that the lack of genetic effects on an agin ...
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Journal ArticleMechanisms of ageing and development · March 2011
We analysed relationship between the risk of onset of "unhealthy life" (defined as the onset of cancer, cardiovascular diseases, or diabetes) and longitudinal changes in body mass index, diastolic blood pressure, hematocrit, pulse pressure, pulse rate, and ...
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Journal ArticleRejuvenation research · August 2010
Relationships between aging, disease risks, and longevity are not yet well understood. For example, joint increases in cancer risk and total survival observed in many human populations and some experimental aging studies may be linked to a trade-off betwee ...
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Journal ArticleBiogerontology · June 2010
Exceptional survival results from complicated interplay between genetic and environmental factors. The effects of these factors on survival are mediated by the biological and physiological variables, which affect mortality risk. In this paper, we evaluated ...
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Journal ArticleMechanisms of ageing and development · May 2010
The Gln(27)Glu polymorphism but not the Arg(16)Gly polymorphism of the beta2-adrenergic receptor (ADRB2) gene appears to be associated with a broad range of aging-associated phenotypes, including cancers at different sites, myocardial infarction (MI), inte ...
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Journal ArticleRejuvenation research · February 2010
Multiple functions of the beta2-adrenergic receptor (ADRB2) and angiotensin-converting enzyme (ACE) genes warrant studies of their associations with aging-related phenotypes. We focus on multimarker analyses and analyses of the effects of compound genotype ...
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Journal ArticleCurr Gerontol Geriatr Res · 2010
It is well known from epidemiology that values of indices describing physiological state in a given age may influence human morbidity and mortality risks. Studies of connection between aging and life span suggest a possibility that dynamic properties of ag ...
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Journal ArticleExperimental gerontology · November 2009
We use unique experimental data on daily reproduction and survival of individual fruit flies from eight cohorts eclosed at different dates in 2004 and 2005 who were treated with varying proportions of sugar and yeast and subject to different caloric restri ...
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Journal ArticleJournal of theoretical biology · May 2009
Many longitudinal studies of aging collect genetic information only for a sub-sample of participants of the study. These data also do not include recent findings, new ideas and methodological concepts developed by distinct groups of researchers. The formal ...
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Journal ArticleRussian Journal of Plant Physiology · January 1, 2009
Diversity of photosynthetic characteristics determined by plant genotypes provides the grounds for the increase in potential crop productivity by means of producing plant forms whose photosynthetic apparatus (PSA) has optimal size and functional efficiency ...
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Journal ArticleThe journals of gerontology. Series A, Biological sciences and medical sciences · January 2009
Aging studies can be facilitated by refocusing from longevity phenotypes to their proxies (intermediate phenotypes). Robust selection of the intermediate phenotypes requires data on such phenotypes and life span measured in the same individuals, which is n ...
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Journal ArticleExperimental gerontology · December 2008
The traditional sex morbidity-mortality paradox that females have worse health but better survival than males is based on studies of major health traits. We applied a cumulative deficits approach to study this paradox, selecting 34 minor health deficits co ...
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Journal ArticleThe journals of gerontology. Series A, Biological sciences and medical sciences · October 2008
We evaluated the predictive potential for long-term (24-year) survival and longevity (85+ years) of an index of cumulative deficits (DI) and six physiological indices (pulse pressure, diastolic blood pressure, pulse rate, serum cholesterol, blood glucose, ...
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Journal ArticleAnnals of epidemiology · September 2008
PurposeHealth of the general population is improving along a number of major health dimensions. Using a cumulative deficits approach, we investigated whether such improvements were evident at the level of minor health traits.MethodsWe sel ...
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Journal ArticleJournal of the American Geriatrics Society · May 2008
ObjectivesTo compare how well frailty measures based on a phenotypic frailty approach proposed in the Cardiovascular Health Study (CHS) and a cumulative deficits approach predict mortality.DesignCohort study.SettingThe main cohor ...
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Journal ArticleRejuvenation research · February 2008
Major musculoskeletal conditions including arthritis represent an increasing burden on individuals and societies. We analyzed the association between self-reported arthritis and mortality in the U.S. elderly disabled and non-disabled individuals using uniq ...
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Journal ArticleJournal of the American Geriatrics Society · January 2008
ObjectivesTo investigate the relationship between body mass index (BMI) and 9-year mortality in older (> or = 65) Americans with and without disability.DesignCohort study.SettingThe unique disability-focused National Long Term Ca ...
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