Journal ArticleAging · 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 ...
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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 ArticleGeroScience · 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 ...
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Journal ArticleTranslational 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 ...
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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 · 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 ArticleTranslational 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 ...
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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 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 ArticlePloS 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 ...
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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 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 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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