Alexander Kulminski

Journal Article GeroScience · June 2025 Genetics is the second strongest risk factor for Alzheimer's disease (AD) after age. More than 70 loci have been implicated in AD susceptibility so far, and the genetic architecture of AD entails both additive and nonadditive contributions from these loci. ... Full text Cite

Methods for joint modeling of longitudinal omics data and time-to-event outcomes: applications to lysophosphatidylcholines in connection to aging and mortality in the Long Life Family Study.

Journal Article Aging · May 2025 Studying the relationships between longitudinal changes in omics variables and event risks requires specific methodologies for joint analyses of longitudinal and time-to-event outcomes. We applied two such approaches (joint models [JM], stochastic process ... Full text Cite

Association of APOE alleles and polygenic profiles comprising APOE-TOMM40-APOC1 variants with Alzheimer's disease neuroimaging markers.

Journal Article Alzheimer's & dementia : the journal of the Alzheimer's Association · February 2025 IntroductionTOMM40 and APOC1 variants can modulate the APOE-ε4-related Alzheimer's disease (AD) risk by up to fourfold. We aim to investigate whether the genetic modulation of ε4-related AD risk is reflected in brain morphology.MethodsWe ... Full text Cite

Basic Science and Pathogenesis

Journal Article Alzheimer'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 ... Full text Cite

Pleiotropic Associations with Alzheimer's Disease and Physical Activity: Sex Differences and the Effects of Environment.

Journal Article International 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 ... Full text Cite

Discovery of genomic and transcriptomic pleiotropy between kidney function and soluble receptor for advanced glycation end products using correlated meta-analyses: The Long Life Family Study.

Journal Article Aging cell · October 2024 Patients with chronic kidney disease (CKD) have increased oxidative stress and chronic inflammation, which may escalate the production of advanced glycation end-products (AGEs). High soluble receptor for AGE (sRAGE) and low estimated glomerular filtration ... Full text Cite

Resistance and resilience to tau pathology in Alzheimer's disease: Effects of age, sex, and APOE alleles.

Journal Article Alzheimer's & dementia (Amsterdam, Netherlands) · October 2024 IntroductionNeurofibrillary tangles (NFTs), a hallmark of tau pathology in Alzheimer's disease (AD), accumulate in the aging brain. However, some individuals remain cognitively intact despite high Braak (III-VI) stages, which characterize NFTs' ac ... Full text Cite

An autoimmune transcriptional circuit drives FOXP3+ regulatory T cell dysfunction.

Journal Article Science translational medicine · August 2024 Autoimmune diseases, among the most common disorders of young adults, are mediated by genetic and environmental factors. Although CD4+FOXP3+ regulatory T cells (Tregs) play a central role in preventing autoimmunity, the mol ... Full text Cite

TOMM40 and APOC1 variants differentiate the impacts of the APOE ε4 allele on Alzheimer's disease risk across sexes, ages, and ancestries.

Journal Article Alzheimer'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 ... Full text Cite

The association between frailty and perceived physical and mental fatigability: The Long Life Family Study.

Conference Journal of the American Geriatrics Society · January 2024 BackgroundHigher levels of frailty, quantified by a frailty index (FI), may be linked to fatigue severity as tasks become more physically and mentally demanding. Fatigue, a component of frailty research, has been ambiguous and inconsistent in its ... Full text Cite

Patterns of Aging Changes in Bodyweight May Predict Alzheimer's Disease.

Journal Article J Alzheimers Dis · 2024 Relationships between patterns of aging-changes in bodyweight and AD are not fully understood. We compared mean age-trajectories of weight between those who did and did not develop late-onset-AD, and evaluated impact of age at maximum weight (AgeMax), and ... Full text Link to item Cite

How are APOE4, changes in body weight, and longevity related? Insights from a causal mediation analysis.

Journal Article Frontiers in aging · January 2024 The ε4 allele of the APOE gene (APOE4) is known for its negative association with human longevity; however, the mechanism is unclear. APOE4 is also linked to changes in body weight, and the latter changes were associated with survival in some ... Full text Cite

Exome-Wide Association Study Identified Clusters of Pleiotropic Genetic Associations with Alzheimer's Disease and Thirteen Cardiovascular Traits.

Journal Article Genes · 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 ... Full text Cite

Interaction Analysis Reveals Complex Genetic Associations with Alzheimer's Disease in the CLU and ABCA7 Gene Regions.

Journal Article Genes · August 2023 Sporadic Alzheimer's disease (AD) is a polygenic neurodegenerative disorder. Single-nucleotide polymorphisms (SNPs) in multiple genes (e.g., CLU and ABCA7) have been associated with AD. However, none of them were characterized as causal varia ... Full text Cite

A robust and fast two-sample test of equal correlations with an application to differential co-expression.

Journal Article Statistics in medicine · July 2023 A robust and fast two-sample test for equal Pearson correlation coefficients (PCCs) is important in solving many biological problems, including, for example, analysis of differential co-expression. However, few existing methods for this test can achieve ro ... Full text Cite

Exogenous exposures shape genetic predisposition to lipids, Alzheimer's, and coronary heart disease in the MLXIPL gene locus.

Journal Article Aging · April 2023 Associations of single nucleotide polymorphisms (SNPs) of the MLXIPL lipid gene with Alzheimer's (AD) and coronary heart disease (CHD) and potentially causal mediation effects of their risk factors, high-density lipoprotein cholesterol (HDL-C) and t ... Full text Cite

Inter- and intra-chromosomal modulators of the APOE ɛ2 and ɛ4 effects on the Alzheimer's disease risk.

Journal Article GeroScience · 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 ... Full text Cite

Prevailing Antagonistic Risks in Pleiotropic Associations with Alzheimer's Disease and Diabetes.

Journal Article Journal 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 ... Full text Cite

Interactions between genes involved in physiological dysregulation and axon guidance: role in Alzheimer's disease.

Journal Article Front Genet · 2023 Dysregulation of physiological processes may contribute to Alzheimer's disease (AD) development. We previously found that an increase in the level of physiological dysregulation (PD) in the aging body is associated with declining resilience and robustness ... Full text Link to item Cite

APOE ɛ4 allele and TOMM40-APOC1 variants jointly contribute to survival to older ages.

Journal Article Aging 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 ... Full text Cite

Genome-wide analysis identified abundant genetic modulators of contributions of the apolipoprotein E alleles to Alzheimer's disease risk.

Journal Article Alzheimer'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 ... Full text Cite

Associations of the APOE ε2 and ε4 alleles and polygenic profiles comprising APOE-TOMM40-APOC1 variants with Alzheimer's disease biomarkers.

Journal Article Aging · 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 ... Full text Cite

Genome-wide analysis of genetic predisposition to common polygenic cancers.

Journal Article Journal of applied genetics · May 2022 Lung, breast, prostate, and colorectal cancers are among the most common and fatal malignancies worldwide. They are mainly caused by multifactorial mechanisms and are genetically heterogeneous. We investigated the genetic architecture of these cancers thro ... Full text Cite

Mediation of the APOE associations with Alzheimer's and coronary heart diseases through body mass index and lipids.

Journal Article GeroScience · April 2022 The APOE ε2/ε3/ε4 polymorphism is associated with multiple non-Mendelian traits, including high- (HDL-C) and low- (LDL-C) density lipoprotein cholesterol, triglycerides, body mass index (BMI), coronary heart disease (CHD), and Alzheimer's disease (AD). Lip ... Full text Cite

NIA Long Life Family Study: Objectives, Design, and Heritability of Cross-Sectional and Longitudinal Phenotypes.

Journal Article The journals of gerontology. Series A, Biological sciences and medical sciences · April 2022 The NIA Long Life Family Study (LLFS) is a longitudinal, multicenter, multinational, population-based multigenerational family study of the genetic and nongenetic determinants of exceptional longevity and healthy aging. The Visit 1 in-person evaluation (20 ... Full text Cite

Allele-specific analysis reveals exon- and cell-type-specific regulatory effects of Alzheimer's disease-associated genetic variants.

Journal Article Translational psychiatry · April 2022 Elucidating regulatory effects of Alzheimer's disease (AD)-associated genetic variants is critical for unraveling their causal pathways and understanding the pathology. However, their cell-type-specific regulatory mechanisms in the brain remain largely unc ... Full text Cite

Definitive roles of TOMM40-APOE-APOC1 variants in the Alzheimer's risk.

Journal Article Neurobiology 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 ... Full text Cite

Pleiotropic predisposition to Alzheimer's disease and educational attainment: insights from the summary statistics analysis.

Journal Article GeroScience · 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 ... Full text Cite

APOE alleles modulate associations of plasma metabolites with variants from multiple genes on chromosome 19q13.3.

Journal Article Frontiers in aging neuroscience · January 2022 The APOE ε2, ε3, and ε4 alleles differentially impact various complex diseases and traits. We examined whether these alleles modulated associations of 94 single-nucleotide polymorphisms (SNPs) harbored by 26 genes in 19q13.3 region with 217 plasma m ... Full text Cite

The ε4-bearing TOMM40-APOE-APOC1 haplotype but not the ε4 allele confers an exceptionally high risk of Alzheimer's disease

Journal Article Alzheimer'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 ... Full text Cite

Protective association of the ε2/ε3 heterozygote with Alzheimer's disease is strengthened by TOMM40-APOE variants in men.

Journal Article Alzheimer'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 ... Full text Cite

Heterogeneity of the Predictive Polygenic Risk Scores for Coronary Heart Disease Age-at-Onset in Three Different Coronary Heart Disease Family-Based Ascertainments.

Journal Article Circulation. Genomic and precision medicine · June 2021 BackgroundPolygenic risk scores (PRS) for coronary heart disease (CHD) may contribute to assess the overall risk of CHD. We evaluated how PRS may influence CHD risk when the distribution of age-at-onset, sex, and family health history differ signi ... Full text Cite

NEBULA is a fast negative binomial mixed model for differential or co-expression analysis of large-scale multi-subject single-cell data.

Journal Article Communications biology · May 2021 The increasing availability of single-cell data revolutionizes the understanding of biological mechanisms at cellular resolution. For differential expression analysis in multi-subject single-cell data, negative binomial mixed models account for both subjec ... Full text Cite

Genome-Wide Analysis of Sex Disparities in the Genetic Architecture of Lung and Colorectal Cancers.

Journal Article Genes · May 2021 Almost all complex disorders have manifested epidemiological and clinical sex disparities which might partially arise from sex-specific genetic mechanisms. Addressing such differences can be important from a precision medicine perspective which aims to mak ... Full text Cite

Decline in biological resilience as key manifestation of aging: Potential mechanisms and role in health and longevity.

Journal Article Mechanisms of ageing and development · March 2021 Decline in biological resilience (ability to recover) is a key manifestation of aging that contributes to increase in vulnerability to death with age eventually limiting longevity even in people without major chronic diseases. Understanding the mechanisms ... Full text Cite

Exome-wide age-of-onset analysis reveals exonic variants in ERN1 and SPPL2C associated with Alzheimer's disease.

Journal Article Translational psychiatry · February 2021 Despite recent discoveries in genome-wide association studies (GWAS) of genomic variants associated with Alzheimer's disease (AD), its underlying biological mechanisms are still elusive. The discovery of novel AD-associated genetic variants, particularly i ... Full text Cite

The ApoE Locus and COVID-19: Are We Going Where We Have Been?

Journal Article The journals of gerontology. Series A, Biological sciences and medical sciences · January 2021 Full text Cite

Interactions Between Genes From Aging Pathways May Influence Human Lifespan and Improve Animal to Human Translation.

Journal Article Frontiers in cell and developmental biology · January 2021 A major goal of aging research is identifying genetic targets that could be used to slow or reverse aging - changes in the body and extend limits of human lifespan. However, majority of genes that showed the anti-aging and pro-survival effects in animal mo ... Full text Cite

Polygenic risk scores: pleiotropy and the effect of environment.

Journal Article GeroScience · 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 ... Full text Cite

Quantitative and Qualitative Role of Antagonistic Heterogeneity in Genetics of Blood Lipids.

Journal Article The 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 ... Full text Cite

Fast Algorithms for Conducting Large-Scale GWAS of Age-at-Onset Traits Using Cox Mixed-Effects Models.

Journal Article Genetics · May 2020 Age-at-onset is one of the critical traits in cohort studies of age-related diseases. Large-scale genome-wide association studies (GWAS) of age-at-onset traits can provide more insights into genetic effects on disease progression and transitions between st ... Full text Cite

Summary-Based Methylome-Wide Association Analyses Suggest Potential Genetically Driven Epigenetic Heterogeneity of Alzheimer's Disease.

Journal Article Journal of clinical medicine · May 2020 Alzheimer's disease (AD) is a progressive neurodegenerative disorder with no curative treatment available. Exploring the genetic and non-genetic contributors to AD pathogenesis is essential to better understand its underlying biological mechanisms, and to ... Full text Cite

Genetics of physiological dysregulation: findings from the long life family study using joint models.

Journal Article Aging · April 2020 Recently, Mahalanobis distance (DM) was suggested as a statistical measure of physiological dysregulation in aging individuals. We constructed DM variants using sets of biomarkers collected at the two visits of the Long Life Family St ... Full text Cite

APOE region molecular signatures of Alzheimer's disease across races/ethnicities.

Journal Article Neurobiology 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 ... Full text Cite

The impact of disregarding family structure on genome-wide association analysis of complex diseases in cohorts with simple pedigrees.

Journal Article Journal of applied genetics · February 2020 The generalized linear mixed models (GLMMs) methodology is the standard framework for genome-wide association studies (GWAS) of complex diseases in family-based cohorts. Fitting GLMMs in very large cohorts, however, can be computationally demanding. Also, ... Full text Cite

Genetic and regulatory architecture of Alzheimer's disease in the APOE region.

Journal Article Alzheimer'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 ... Full text Cite

Composite Measure of Physiological Dysregulation as a Predictor of Mortality: The Long Life Family Study.

Journal Article Frontiers in public health · January 2020 Biological aging results in changes in an organism that accumulate over age in a complex fashion across different regulatory systems, and their cumulative effect manifests in increased physiological dysregulation (PD) and declining robustness and resilienc ... Full text Cite

Haplotype architecture of the Alzheimer's risk in the APOE region via co-skewness.

Journal Article Alzheimer'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 ... Full text Cite

Genome-wide linkage analysis of carotid artery traits in exceptionally long-lived families.

Journal Article Atherosclerosis · December 2019 Background and aimsAtherosclerosis develops with age and is partially controlled by genetics. Research to date has identified common variants with small effects on atherosclerosis related traits. We aimed to use family-based genome-wide linkage an ... Full text Cite

Polygenic risk score for disability and insights into disability-related molecular mechanisms.

Journal Article GeroScience · 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 ... Full text Cite

The Alzheimer's Disease Exposome.

Journal Article Alzheimer's & dementia : the journal of the Alzheimer's Association · September 2019 IntroductionEnvironmental factors are poorly understood in the etiology of Alzheimer's disease (AD) and related dementias. The importance of environmental factors in gene environment interactions (GxE) is suggested by wide individual differences i ... Full text Cite

Genetic heterogeneity of Alzheimer's disease in subjects with and without hypertension.

Journal Article GeroScience · April 2019 Alzheimer's disease (AD) is a progressive neurodegenerative disorder caused by the interplay of multiple genetic and non-genetic factors. Hypertension is one of the AD risk factors that has been linked to underlying pathological changes like senile plaques ... Full text Cite

"Physiological Dysregulation" as a Promising Measure of Robustness and Resilience in Studies of Aging and a New Indicator of Preclinical Disease.

Journal Article The journals of gerontology. Series A, Biological sciences and medical sciences · March 2019 Recently suggested novel implementation of the statistical distance measure (DM) for evaluating "physiological dysregulation" (PD) in aging individuals (based on measuring deviations of multiple biomarkers from baseline or normal physiological states) allo ... Full text Cite

Independent associations of TOMM40 and APOE variants with body mass index.

Journal Article Aging 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 ... Full text Cite

Genome-wide analysis of genetic predisposition to Alzheimer's disease and related sex disparities.

Journal Article Alzheimer's research & therapy · January 2019 BackgroundAlzheimer's disease (AD) is the most common cause of dementia in the elderly and the sixth leading cause of death in the United States. AD is mainly considered a complex disorder with polygenic inheritance. Despite discovering many susce ... Full text Cite

Pleiotropic Meta-Analysis of Age-Related Phenotypes Addressing Evolutionary Uncertainty in Their Molecular Mechanisms.

Journal Article Frontiers 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 ... Full text Cite

The impact of APOE genotype on survival: Results of 38,537 participants from six population-based cohorts (E2-CHARGE).

Journal Article PloS one · January 2019 BackgroundApolipoprotein E is a glycoprotein best known as a mediator and regulator of lipid transport and uptake. The APOE-ε4 allele has long been associated with increased risks of Alzheimer's disease and mortality, but the effect of the less pr ... Full text Cite

Evaluation of the Genetic Variance of Alzheimer's Disease Explained by the Disease-Associated Chromosomal Regions.

Journal Article Journal of Alzheimer's disease : JAD · January 2019 Heritability analysis of complex traits/diseases is commonly performed to obtain illustrative information about the potential contribution of the genetic factors to their phenotypic variances. In this study, we investigated the narrow-sense heritability (h ... Full text Cite

Genetics of Human Longevity From Incomplete Data: New Findings From the Long Life Family Study.

Journal Article The journals of gerontology. Series A, Biological sciences and medical sciences · October 2018 The special design of the Long Life Family Study provides a unique opportunity to investigate the genetics of human longevity by analyzing data on exceptional lifespans in families. In this article, we performed two series of genome wide association studie ... Full text Cite

Apolipoprotein E region molecular signatures of Alzheimer's disease.

Journal Article Aging 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 ... Full text Cite

Causal effects of cardiovascular risk factors on onset of major age-related diseases: A time-to-event Mendelian randomization study.

Journal Article Experimental 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 ... Full text Cite

Hidden heterogeneity in Alzheimer's disease: Insights from genetic association studies and other analyses.

Journal Article Experimental 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 ... Full text Cite

Strong impact of natural-selection-free heterogeneity in genetics of age-related phenotypes.

Journal Article Aging · 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 ... Full text Cite

How Well Does the Family Longevity Selection Score Work: A Validation Test Using the Utah Population Database.

Journal Article Frontiers in public health · January 2018 The Family Longevity Selection Score (FLoSS) was used to select families for the Long Life Family Study (LLFS) but has never been validated in other populations. The goal of this paper is to validate how well the FLoSS-based selection procedure works in an ... Full text Cite

The APOE ε4 allele is associated with a reduction in FEV1/FVC in women: A cross-sectional analysis of the Long Life Family Study.

Journal Article PloS one · January 2018 IntroductionMurine studies have shown that apolipoprotein E modulates pulmonary function during development, aging, and allergen-induced airway disease. It is not known whether the polymorphic human APOE gene influences pulmonary function.Obje ... Full text Cite

A genetic stochastic process model for genome-wide joint analysis of biomarker dynamics and disease susceptibility with longitudinal data.

Journal Article Genetic epidemiology · November 2017 Unraveling the underlying biological mechanisms or pathways behind the effects of genetic variations on complex diseases remains one of the major challenges in the post-GWAS (where GWAS is genome-wide association study) era. To further explore the relation ... Full text Cite

Identification of polymorphisms in cancer patients that differentially affect survival with age.

Journal Article Aging · October 2017 The World Health Organization predicts that the proportion of the world's population over 60 will almost double from 12% to 22% between 2015 and 2050. Ageing is the biggest risk factor for cancer, which is a leading cause of deaths worldwide. Unfortunately ... Full text Cite

Uncoupling associations of risk alleles with endophenotypes and phenotypes: insights from the ApoB locus and heart-related traits.

Journal Article Aging 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 ... Full text Open Access Cite

A review of the biomedical innovations for healthy longevity.

Journal Article Aging · January 2017 Full text Cite

Corrigendum: Pleiotropic Meta-Analyses of Longitudinal Studies Discover Novel Genetic Variants Associated with Age-Related Diseases.

Journal Article Frontiers in genetics · January 2017 [This corrects the article on p. 179 in vol. 7, PMID: 27790247.]. ... Full text Cite

Protective role of the apolipoprotein E2 allele in age-related disease traits and survival: evidence from the Long Life Family Study.

Journal Article Biogerontology · 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 ... Full text Open Access Cite

High-Resolution Analyses of Effects of Polygenic Risk Scores on Time-to-Event Outcomes in Longitudinal Studies

Conference GENETIC EPIDEMIOLOGY · November 1, 2016 Link to item Cite

Pleiotropic Associations of Allelic Variants in a 2q22 Region with Risks of Major Human Diseases and Mortality.

Journal Article PLoS 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. ... Full text Cite

Extensive Pleiotropy with Age-Related Disease Traits: The Candidate Gene Association Resource

Conference GERONTOLOGIST · November 1, 2016 Link to item Cite

GENETIC PREDISPOSITION TO AGE-RELATED PHENOTYPES IN THE LIGHT OF EVOLUTION

Conference The Gerontologist · November 2016 Full text Cite

PLEIOTROPIC META-ANALYSIS IDENTIFIES SHARED GENETIC CONNECTIONS BETWEEN DISTINCT AGE-RELATED TRAITS

Conference The Gerontologist · November 2016 Full text Cite

GENES WITH PLEIOTROPIC EFFECTS ON AGING-RELATED TRAITS IN HUMANS

Conference The Gerontologist · November 2016 Full text Cite

A NOVEL ALLELIC VARIANT IN A 2Q22 REGION CONFERS RISKS OF MAJOR HUMAN DISEASES AND MORTALITY

Conference The Gerontologist · November 2016 Full text Cite

Explicating heterogeneity of complex traits has strong potential for improving GWAS efficiency.

Journal Article Scientific 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 ... Full text Open Access Cite

Resistance to stresses and reliability of biological systems: Insights for genetic studies of human aging, health, and longevity

Conference Proceedings 2nd International Symposium on Stochastic Models in Reliability Engineering Life Science and Operations Management Smrlo 2016 · March 11, 2016 Connection between stress resistance and longevity in biological organisms is widely discussed and confirmed experimentally. Much less is known about the roles of genetic and non-genetic factors in regulation of such connection. Earlier studies emphasized ... Full text Open Access Cite

Puzzling role of genetic risk factors in human longevity: "risk alleles" as pro-longevity variants.

Journal Article Biogerontology · February 2016 Complex diseases are major contributors to human mortality in old age. Paradoxically, many genetic variants that have been associated with increased risks of such diseases are found in genomes of long-lived people, and do not seem to compromise longevity. ... Full text Open Access Cite

How the effects of aging and stresses of life are integrated in mortality rates: insights for genetic studies of human health and longevity.

Journal Article Biogerontology · 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 ... Full text Open Access Cite

Optimal Versus Realized Trajectories of Physiological Dysregulation in Aging and Their Relation to Sex-Specific Mortality Risk.

Journal Article Frontiers in public health · January 2016 While longitudinal changes in biomarker levels and their impact on health have been characterized for individual markers, little is known about how overall marker profiles may change during aging and affect mortality risk. We implemented the recently devel ... Full text Open Access Cite

How Genes Modulate Patterns of Aging-Related Changes on the Way to 100: Biodemographic Models and Methods in Genetic Analyses of Longitudinal Data.

Journal Article North 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 ... Full text Open Access Cite

Pleiotropic Meta-Analyses of Longitudinal Studies Discover Novel Genetic Variants Associated with Age-Related Diseases.

Journal Article Frontiers 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 ... Full text Open Access Cite

Pure and Confounded Effects of Causal SNPs on Longevity: Insights for Proper Interpretation of Research Findings in GWAS of Populations with Different Genetic Structures.

Journal Article Frontiers 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 ... Full text Open Access Cite

Conclusions Regarding Empirical Patterns of Aging, Health, and Longevity

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 ... Full text Cite

Conclusions Regarding Statistical Modeling of Aging, Health, and Longevity

Chapter · January 1, 2016 The analyses conducted in Part I did not exhaust all factors affecting age patterns of age-related changes in health and mortality. They actually provided a strong rationale for conducting more detailed analyses which require advanced methods of mathematic ... Full text Cite

Approaches to Statistical Analysis of Longitudinal Data on Aging, Health, and Longevity: Biodemographic Perspectives

Chapter · January 1, 2016 Longitudinal data play a pivotal role in discovering different aspects of knowledge related to aging, health, and longevity. There are many statistical methods for the analysis of longitudinal data, which is one of the most prolific areas of statistical sc ... Full text Cite

Continuing the Search for Determinants of Healthy Life Span and Longevity

Chapter · January 1, 2016 Life expectancy in humans worldwide has been experiencing dramatic increases for the past two centuries (Oeppen and Vaupel 2002). In most countries, the extension of lifespan is associated with a transition from a long historical period of high fertility a ... Full text Cite

Dynamic Characteristics of Aging-Related Changes as Predictors of Longevity and Healthy Lifespan

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 ... Full text Cite

The Complex Role of Genes in Diseases and Traits in Late Life: An Example of the Apolipoprotein E Polymorphism

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 ... Full text Cite

Stochastic Process Models of Mortality and Aging

Chapter · January 1, 2016 A better understanding of relationships among human aging, health, and longevity requires integrative statistical methods capable of taking into account relevant knowledge accumulated in the field when extracting useful information from the data. In this c ... Full text Cite

Indices of Cumulative Deficits

Chapter · January 1, 2016 Despite broad interest in the mechanisms responsible for human aging and numerous efforts to identify factors contributing to morbidity, biological senescence, and longevity, these processes still remain elusive. This makes the systemic description of agin ... Full text Cite

Evidence for Dependence Among Diseases

Chapter · January 1, 2016 Demographic calculations evaluating the role of chronic diseases in life expectancy use the assumption that diseases are independent. Disease independence was a plausible hypothesis in the era of infectious diseases. However, the health problems of modern ... Full text Cite

Age Trajectories of Physiological Indices: Which Factors Influence Them?

Chapter · January 1, 2016 Longitudinal data on aging, health, and longevity provide researchers with a unique opportunity to observe aging-related changes in biomarkers that describe the functioning of individual organisms during people’s life courses. In this chapter, empirical es ... Full text Cite

Integrative Mortality Models for the Study of Aging, Health, and Longevity: Benefits of Combining Data

Chapter · January 1, 2016 In a number of longitudinal studies, individual health and physiological/biological variables are repeatedly measured for a relatively large number of study subjects. Such data have good potential for evaluating properties of dynamic mechanisms involved in ... Full text Cite

Integrative Mortality Models with Parameters That Have Biological Interpretations

Chapter · January 1, 2016 Mortality rates are important characteristics of life span distributions that integrate the influences of many external and internal factors affecting individuals in the population during their life course. These include the ontogenetic program, individual ... Full text Cite

Factors That May Increase Vulnerability to Cancer and Longevity in Modern Human Populations

Chapter · January 1, 2016 Cancer incidence rates for all disease sites combined and life expectancy have increased over time in many countries around the world. These increases were concurrent with economic progress and the spread of the Western lifestyle. Overall cancer risk and l ... Full text Cite

On Approaches to Improve Power in Analyses of Genetic Effects on Time-To-Event Outcomes in Longitudinal Studies

Conference GENETIC EPIDEMIOLOGY · November 1, 2015 Link to item Cite