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The von Hippel-Lindau (VHL) tumor suppressor gene plays a prominent role in the development of hemangioblastomas (HBs) within specific regions of the human' central nervous system (CNS). Alterations in VHL gene are rarely observed in... more
The von Hippel-Lindau (VHL) tumor suppressor gene plays a prominent role in the development of hemangioblastomas (HBs) within specific regions of the human' central nervous system (CNS). Alterations in VHL gene are rarely observed in the more common features of human VHL-related tumors in animal models, and VHL heterozygous knockout (VHL + / -) mice do not develop HBs. We tested whether VHL heterozygous knockout mice exhibited genetic predisposition to the development of HBs and conferred a selective advantage involving growth of blood vessels to its carrier. No differences were observed between wild-type and VHL + /- mice in development ad reproduction. The heterozygous VHL + /- mice did not develop higher genetic susceptibility to CNS-HBs over their lifetime. Furthermore, this recessive VHL gene heterozygosity is relatively stable. Interestingly, we found these heterozygous VHL + /- mice gained an advantage conferring to angiogenic ability in a particular environment, compared...
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We conduct a systematic comparison of the performance of four commonly used value combination methods applied to panel unit root tests: the original Fisher test, the modified inverse normal method, Simes test, and the modified truncated... more
We conduct a systematic comparison of the performance of four commonly used value combination methods applied to panel unit root tests: the original Fisher test, the modified inverse normal method, Simes test, and the modified truncated product method (TPM). Our simulation results show that under cross-section dependence the original Fisher test is severely oversized, but the other three tests exhibit good size properties. Simes test is powerful when the total evidence against the joint null hypothesis is concentrated in one or very few of the tests being combined, but the modified inverse normal method and the modified TPM have good performance when evidence against the joint null is spread among more than a small fraction of the panel units. These differences are further illustrated through one empirical example on testing purchasing power parity using a panel of OECD quarterly real exchange rates.
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Increased water activity in peanut butter significantly ( P < 0.05) reduced the heat resistance of desiccation-stressed Salmonella enterica serotypes treated at 90°C. The difference in thermal resistance was less notable when strains... more
Increased water activity in peanut butter significantly ( P < 0.05) reduced the heat resistance of desiccation-stressed Salmonella enterica serotypes treated at 90°C. The difference in thermal resistance was less notable when strains were treated at 126°C. Using scanning electron microscopy, we observed minor morphological changes of S. enterica cells resulting from desiccation and rehydration processes in peanut oil.
Research Interests: Chemistry, Food Science, Water, Biology, Scanning Electron Microscopy, and 14 moreMedicine, Multidisciplinary, Food Microbiology, Applied Environmental Microbiology, Desiccation, Salmonella, Fats, CARBOHYDRATES, Microbial Viability, Arachis Hypogaea, Plant Oils, Serotyping, Serotype, and Salmonella enterica
Significant differences ( P < 0.05) were found between the survival rates of Salmonella enterica and Escherichia coli O157:H7 in peanut butter with different formulations and water activity. High carbohydrate content in peanut butter... more
Significant differences ( P < 0.05) were found between the survival rates of Salmonella enterica and Escherichia coli O157:H7 in peanut butter with different formulations and water activity. High carbohydrate content in peanut butter and low incubation temperature resulted in higher levels of bacterial survival during storage but lower levels of bacterial resistance to heat treatment.
Research Interests: Microbiology, Food Science, Biology, Medicine, Multidisciplinary, and 15 moreFood Microbiology, Lipids, Incubation, Escherichia coli, Applied Environmental Microbiology, Enterobacteriaceae, Proteins, Salmonella, CARBOHYDRATES, Microbial Viability, Arachis Hypogaea, Sodium Chloride, Butter, Heat resistance, and Salmonella enterica
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The inflammatory hypothesis posits that sustained neuroinflammation is sufficient to induce neurodegeneration and the development of Alzheimer’s disease (AD) and Alzheimer’s dementia. One potential source of inflammation is the intestine... more
The inflammatory hypothesis posits that sustained neuroinflammation is sufficient to induce neurodegeneration and the development of Alzheimer’s disease (AD) and Alzheimer’s dementia. One potential source of inflammation is the intestine which harbors pro-inflammatory microorganisms capable of promoting neuroinflammation. Systemic inflammation is robustly associated with neuroinflammation as well as low levels of brain derived neurotrophic factor (BDNF) in the systemic circulation and brain. Thus, in this pilot study, we tested the hypothesis that intestinal barrier dysfunction precedes risk of death, incident AD dementia and MCI, cognitive impairment and neuropathology. Serum BDNF was associated with changes in global cognition, working memory, and perceptual speed but not risk of death, incident AD dementia, incident MCI, or neuropathology. Neither of the markers of intestinal barrier integrity examined, including lipopolysaccharide binding protein (LBP) nor intestinal fatty acid ...
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We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A... more
We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12–16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI’s magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57.
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ABSTRACTGenetic variants within nearly 1,000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings... more
ABSTRACTGenetic variants within nearly 1,000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2,286 lipid associations by combining six gene prediction methods and assigning a confidence score. We assign, most confidently, 118 candidate causal genes and identify potential drug targets including bona-fide (PCSK9) and putative (PNLIPandARF6) genes. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically-predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with c...
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Mitochondrial DNA copy number (mtDNA-CN) measured from blood specimens is a minimally invasive marker of mitochondrial function that exhibits both inter-individual and intercellular variation. To identify genes involved in regulating... more
Mitochondrial DNA copy number (mtDNA-CN) measured from blood specimens is a minimally invasive marker of mitochondrial function that exhibits both inter-individual and intercellular variation. To identify genes involved in regulating mitochondrial function, we performed a genome-wide association study (GWAS) in 465,809 White individuals from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank (UKB). We identified 133 SNPs with statistically significant, independent effects associated with mtDNA-CN across 100 loci. A combination of fine-mapping, variant annotation, and co-localization analyses were used to prioritize genes within each of the 133 independent sites. Putative causal genes were enriched for known mitochondrial DNA depletion syndromes (p= 3.09 x 10−15) and the gene ontology (GO) terms for mtDNA metabolism (p= 1.43 x 10−8) and mtDNA replication (p= 1.2 x 10−7). A clustering approach leveraged pleiotropy between mtDNA-CN a...
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ObjectiveTo assess whether neurodegenerative pathologies are differentially related to trajectories of change in different cognitive abilities.MethodsAt annual intervals for up to 21 years, 915 older participants in a longitudinal... more
ObjectiveTo assess whether neurodegenerative pathologies are differentially related to trajectories of change in different cognitive abilities.MethodsAt annual intervals for up to 21 years, 915 older participants in a longitudinal clinical-pathologic cohort study completed a battery of 15 tests from which previously established composite measures of episodic memory, semantic memory, working memory, and perceptual speed were derived. At death, they underwent a neuropathologic examination to quantify Alzheimer disease pathology, Lewy bodies, transactive response DNA-binding protein 43 (TDP-43) pathology, and hippocampal sclerosis plus multiple markers of cerebrovascular disease. Time-varying effect models were used to assess change over time in the relation of neuropathologic markers to cognitive trajectories.ResultsControlling for pathology, decline in perceptual speed was evident about 15 years before death; modest decline in semantic and working memory occurred later; and there was...
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Humans vary substantially in their willingness to take risks. In a combined sample of over one million individuals, we conducted genome-wide association studies (GWAS) of general risk tolerance, adventurousness, and risky behaviors in the... more
Humans vary substantially in their willingness to take risks. In a combined sample of over one million individuals, we conducted genome-wide association studies (GWAS) of general risk tolerance, adventurousness, and risky behaviors in the driving, drinking, smoking, and sexual domains. We identified 611 approximately independent genetic loci associated with at least one of our phenotypes, including 124 with general risk tolerance. We report evidence of substantial shared genetic influences across general risk tolerance and risky behaviors: 72 of the 124 general risk tolerance loci contain a lead SNP for at least one of our other GWAS, and general risk tolerance is moderately to strongly genetically correlated (to 0.50) with a range of risky behaviors. Bioinformatics analyses imply that genes near general-risk-tolerance-associated SNPs are highly expressed in brain tissues and point to a role for glutamatergic and GABAergic neurotransmission. We find no evidence of enrichment for gen...
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Hemangioblastomas (HBs) are uncommon tumors characterized by the presence of inactivating alterations in the von Hippel-Lindau (VHL) gene in inherited cases and by infrequent somatic mutation in sporadic entities. We performed whole exome... more
Hemangioblastomas (HBs) are uncommon tumors characterized by the presence of inactivating alterations in the von Hippel-Lindau (VHL) gene in inherited cases and by infrequent somatic mutation in sporadic entities. We performed whole exome sequencing on 11 HB patients to further elucidate the genetics of HBs. A total of 270 somatic variations in 219 genes, of which there were 86 mutations in 67 genes, were found in sporadic HBs, and 184 mutations were found in 154 genes in familial HBs. C: G>T: A and T: A>C: G mutations are relatively common in most HB patients. Genes harboring the most significant mutations include PCDH9, KLHL12, DCAF4L1, and VHL in sporadic HBs, and ZNF814, DLG2, RIMS1, PNN, and MUC7 in familial HBs. The frequency of CNV varied considerably within sporadic HBs but was relatively similar within familial HBs. Five genes, including OTOGL, PLCB4, SCEL, THSD4, and WWOX, have CNVs in the six patients with sporadic HBs, and three genes, including ABCA6, CWC27, and L...
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The objective of this study was to examine whether the effects of age-related neuropathologies on cognition change over time. Participants were 1096 deceased persons from two clinical-pathologic studies. All were without dementia at... more
The objective of this study was to examine whether the effects of age-related neuropathologies on cognition change over time. Participants were 1096 deceased persons from two clinical-pathologic studies. All were without dementia at baseline, completed a detailed battery of cognitive tests annually over up to 21 years, died, and underwent detailed neuropathologic examinations to identify Alzheimer's disease pathology, vascular pathologies (i.e. macro- and microscopic infarcts, atherosclerosis, arteriolar sclerosis, and cerebral amyloid angiopathy), Lewy bodies, transactive response DNA-binding protein 43 (TDP-43) pathology, and hippocampal sclerosis. A time-varying effects model was used to flexibly characterize the trajectory of global cognition and assess whether the effects of demographics and each neuropathologic index on cognition changed over time. Results indicated that the mean trajectory of global cognition was characterized by gradual cognitive decline beginning ∼15 ye...
Research Interests: Psychology, Dementia, Cognition, Aging, Neuropathology, and 15 moreMedicine, Brain, Humans, Female, Male, Aged, Longitudinal Studies, Cerebral amyloid angiopathy, Cognitive Decline, Cognition disorders, Statistics as Topic, Neuropsychological Tests, Hippocampal Sclerosis, Psychology and Cognitive Sciences, and Medical and Health Sciences
The objective of this study was to compare long-term surgical outcomes and complications of laparoscopy-assisted distal gastrectomy (LADG) with open distal gastrectomy (ODG) for the treatment of early gastric cancer (EGC) based on a... more
The objective of this study was to compare long-term surgical outcomes and complications of laparoscopy-assisted distal gastrectomy (LADG) with open distal gastrectomy (ODG) for the treatment of early gastric cancer (EGC) based on a review of available randomized controlled trials (RCTs) evaluated using the Cochrane methodology.RCTs comparing LADG and ODG were identified by a systematic literature search in PubMed, Cochrane Library, MEDLINE, EMBASE, Scopus, and the China Knowledge Resource Integrated Database, for papers published from January 1, 2003 to July 30, 2015. Meta-analyses were performed to compare the long-term clinical outcomes.Our systematic literature search identified 8 eligible RCTs including 732 patients (374 LADGs and 358 ODGs), with low overall risk of bias. Long-term mortality and relapse rate were comparable for both techniques. The long-term complication rate was 8.47% in LADG groups and 13.62% in the ODG group, indicating that LADG was associated with lower ri...
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Multiple sclerosis (MS) is the most frequent nontraumatic disabling neurological disease among young adults. Previous studies have examined the association of rs703842 in CYP27B1 with MS susceptibility, with inconsistent results... more
Multiple sclerosis (MS) is the most frequent nontraumatic disabling neurological disease among young adults. Previous studies have examined the association of rs703842 in CYP27B1 with MS susceptibility, with inconsistent results reported.The objective of this study is to conduct a systematic literature search and perform meta-analyses to examine whether rs703842 is associated with MS risk.We searched potential literature in PubMed, Cochrane Library, Embase, Google Scholar, Web of Science, and HuGE by using the following inclusion criteria: studies were on human subjects; the studies were case-control studies; studies included subjects who had MS and those who did not have MS; and the studies provided genotype data for rs703842 for subjects who had and did not have MS, or provided odds ratios (ORs) and the 95% confidence intervals (CIs) for assessing the association of rs703842 with MS, or provided sufficient data for the calculation of OR and the 95% CI. We used random-effects model...
Research Interests: Genetics, Multiple sclerosis, Medicine, Humans, Female, and 15 moreMale, Polymorphism (computer Science), Young Adult, Meta Analysis, Publication Bias, Clinical Sciences, Adult, Odds ratio, Genetic Polymorphism, European Continental Ancestry Group, Confidence Interval, Case Control Studies, Funnel Plot, alleles, and Genetic predisposition to disease
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Background: Intraocular pressure (IOP) is a major modifiable risk factor for glaucoma. However, the mechanisms underlying the controlling of IOP remain to be elucidated. Objective: To prioritize genes that are pleiotropically associated... more
Background: Intraocular pressure (IOP) is a major modifiable risk factor for glaucoma. However, the mechanisms underlying the controlling of IOP remain to be elucidated. Objective: To prioritize genes that are pleiotropically associated with IOP. Methods: We adopted a two-sample Mendelian randomization method, named summary-based Mendelian randomization (SMR), to examine the pleiotropic effect of gene expression on IOP. The SMR analyses were based on summarized data from a genome-wide association study (GWAS) on IOP. We conducted separate SMR analyses using Genotype-Tissue Expression (GTEx) and Consortium for the Architecture of Gene Expression (CAGE) expression quantitative trait loci (eQTL) data. Additionally, we performed a transcriptome-wide association study (TWAS) to identify genes whose cis-regulated expression levels were associated with IOP. Results: We identified 19 and 25 genes showing pleiotropic association with IOP using the GTEx and CAGE eQTL data, respectively. RP11-...
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Background The pathogenesis of dental caries remains unclear, with increasing evidence suggesting that genetic susceptibility plays an essential role. Previous studies have reported the association between genetic polymorphisms in... more
Background The pathogenesis of dental caries remains unclear, with increasing evidence suggesting that genetic susceptibility plays an essential role. Previous studies have reported the association between genetic polymorphisms in lactotransferrin (LTF) and the risk of dental caries with inconsistent results. Methods A systematic literature search of the PubMed, Cochrane Library, HuGE and Google Scholar databases was performed by two authors independently for papers published before December 5, 2019 on the association between genetic variants in LTF and the risk of dental caries. We adopted the subsequent inclusion criteria to assess study eligibility: 1) The studies were based on human subjects; 2) the presence of dental caries should be screened for in both the case group and the control group; and 3) genotype data on variants in LTF were available in both the case group and the control group. We calculated odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) by ...
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In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close... more
In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in F...
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Alteration of ex vivo magnetic resonance imaging transverse relaxation is associated with late-life cognitive decline even after controlling for common neuropathologic conditions. However, the underlying neurobiology of this association... more
Alteration of ex vivo magnetic resonance imaging transverse relaxation is associated with late-life cognitive decline even after controlling for common neuropathologic conditions. However, the underlying neurobiology of this association is unknown. To investigate the association between brain gene expression, DNA methylation, and alteration of magnetic resonance imaging transverse relaxation in late-life cognitive decline. Data came from 2 community-based longitudinal cohort studies of aging and dementia, the Religious Orders Study, which began in 1993, and the Rush Memory and Aging Project, which began in 1997. All participants agreed to undergo annual clinical evaluations and to donate their brains after death. By October 24, 2016, a total of 1358 individuals had died and had brain autopsies that were approved by board-certified neuropathologists. Of those, 552 had undergone ex vivo imaging. The gene expression analysis was limited to 174 individuals with both imaging and brain RN...
Research Interests: Magnetic Resonance Imaging, Medicine, Gene expression, Hippocampus, Brain, and 15 moreHumans, Methylation, Functional Magnetic Resonance Imaging, Female, Male, DNA methylation, Autopsy, Longitudinal Studies, Cognitive Decline, Alzheimer Disease, DNA binding proteins, Cohort Studies, Cognitive dysfunction, Sclerosis, and Lewy bodies
Research Interests: Biomarkers, Medicine, Logistic Regression, Humans, Internal Medicine, and 15 moreBlood Glucose, Diabetes mellitus, Diabetic Retinopathy, Female, Male, Peptides, Aged, Middle Aged, Sex Factors, Bone remodeling, Type 2 Diabetes Mellitus, Cross Sectional Studies, Macular edema, Medical and Health Sciences, and Collagen type I
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Patterns of linkage between the ε4 allele of Apolipoprotein E (APOE) and '523 poly-T alleles in the adjacent gene, TOMM40, differ between Caucasian and African Americans. The extent to which this difference affects the risk of... more
Patterns of linkage between the ε4 allele of Apolipoprotein E (APOE) and '523 poly-T alleles in the adjacent gene, TOMM40, differ between Caucasian and African Americans. The extent to which this difference affects the risk of Alzheimer's disease (AD) is unclear. We compared the APOE ε4-TOMM40 '523 haplotypes between older Caucasian and African Americans, and examined their relationship with AD dementia. Data came from three community based cohort studies of diverse participants. APOE genotypes were determined by polymorphisms of rs429358 and rs7412. TOMM40 '523 genotypes were defined by the poly-T repeat length of rs10524523 (short ['523-S]: poly-T ≤ 19, long ['523-L]: 20 ≤ poly-T ≤ 29, and very long ['523-VL]: poly-T ≥ 30). Cox proportional hazards models examined the effect of haplotype variation on the risk of incident AD dementia. A total of 1,848 Caucasian and 540 African American individuals were included in the study. In Caucasians, nearly none (0...
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DNA methylation is a key epigenetic mechanism in brain aging and Alzheimer's disease (AD). The newly discovered 5-hydroxymethylcytosine mediates DNA demethylation, is highly abundant in the brain, and is dynamically regulated by life... more
DNA methylation is a key epigenetic mechanism in brain aging and Alzheimer's disease (AD). The newly discovered 5-hydroxymethylcytosine mediates DNA demethylation, is highly abundant in the brain, and is dynamically regulated by life experiences. However, little is known about its genome-wide patterns and potential role in AD. Using a genome-wide capture followed by high-throughput sequencing, we studied the genome-wide distribution of 5-hydroxymethylcytosine at specific genomic loci in human AD brain and identified differentially hydroxymethylated regions (DhMRs) associated with AD pathology. We identified 517 DhMRs significantly associated with neuritic plaques and 60 DhMRs associated with neurofibrillary tangles. DNA hydroxymethylation in gene bodies was predominantly positively correlated with cis-acting gene expression. Moreover, genes showing differential hydroxymethylation were significantly enriched in neurobiological processes and clustered in functional gene ontology c...
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Diabetic retinopathy (DR) is a major sight-threatening diabetic complication. Previous studies have examined the association of DR with multiple genetic variants in the receptor for advanced glycation end products (RAGE) gene, with... more
Diabetic retinopathy (DR) is a major sight-threatening diabetic complication. Previous studies have examined the association of DR with multiple genetic variants in the receptor for advanced glycation end products (RAGE) gene, with inconsistent results. To perform a systematic literature search and conduct meta-analyses to examine the association of genetic variants in RAGE with DR. PubMed, Cochrane Library, Embase, Google Scholar, and HuGE. Studies were on human subjects; the studies were case-control ones and included subjects who had DR and those who did not have DR; and the studies provided genotype data for genetic variants in RAGE, separately for subjects who had and did not have DR, or provided odds ratios (ORs) and the 95% confidence intervals (CIs), or provided sufficient data for the calculation of OR and the 95% CI. We used OR as a measure of association, and used random-effects model in all the meta-analyses. Between-study heterogeneity was assessed using I, and publicat...
Research Interests: Medicine, Glycation, Humans, Internal Medicine, Diabetic Retinopathy, and 12 moreRisk factors, Meta Analysis, Publication Bias, Clinical Sciences, Genotype, Single Nucleotide Polymorphism, Odds ratio, Genetic variation, Risk Factors, Genetic Association, Confidence Interval, and Case Control Studies
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General DNA hypomethylation is associated with Alzheimer's disease (AD), but it is unclear when DNA hypomethylation starts or plays a role in AD pathology or whether DNA re-methylation would rescue early amyloid-related cognitive... more
General DNA hypomethylation is associated with Alzheimer's disease (AD), but it is unclear when DNA hypomethylation starts or plays a role in AD pathology or whether DNA re-methylation would rescue early amyloid-related cognitive impairments. In an APP transgenic mouse model of AD-like amyloid pathology we found that early intraneuronal amyloid beta build-up is sufficient to unleash a global and beta-site amyloid precursor protein cleaving enzyme 1 (bace-1) DNA demethylation in AD-vulnerable brain regions. S-adenosylmethionine administration at these early stages abolished this hypomethylation, diminished the amyloid pathology and restored cognitive capabilities. To assess a possible human significance of findings, we examined the methylation at 12 CpGs sites in the bace-1 promoter, using genome-wide DNA methylation data from 740 postmortem human brains. Thus, we found significant associations of bace-1 promoter methylation with β-amyloid load among persons with AD dementia, and...
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We investigated the change in DNA methylation in peripheral blood CD4+ lymphocytes over time, examined the relation between CD4+ lymphocytes and brain methylation, and compared their associations with AD pathology. Genome-wide methylation... more
We investigated the change in DNA methylation in peripheral blood CD4+ lymphocytes over time, examined the relation between CD4+ lymphocytes and brain methylation, and compared their associations with AD pathology. Genome-wide methylation was measured three times in 41 older persons using Illumina Infinium HumanMethylation450 array. The two CD4+ lymphocytes measures were at study baseline and proximate to death. Brain tissue came from frozen dorsolateral prefrontal cortex. Global methylation features were conserved across tissue. At individual CpG sites, methylation level was concordant between the two CD4+ lymphocytes but more diffuse between CD4+ lymphocytes and brain. Previous associations of brain methylation with neuritic plaques at target methylation sites were not replicated in CD4+ lymphocytes. There is no strong evidence of change in CD4+ lymphocytes methylation among older persons over an average of 7.5 years. Methylation associations with AD pathology found in neocortex a...
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To evaluate prognostic significance of phosphoglycerate kinase 1 (PGK1) protein expression in patients with gallbladder cancer (GBC).Ninety-five patients who underwent surgical resection for GBC between January 2004 and December 2010 were... more
To evaluate prognostic significance of phosphoglycerate kinase 1 (PGK1) protein expression in patients with gallbladder cancer (GBC).Ninety-five patients who underwent surgical resection for GBC between January 2004 and December 2010 were enrolled. Overall survival (OS) and disease-free survival (DFS) were evaluated over a 10-year follow-up. PGK1 expression was assessed by tissue microarray and immunohistochemistry. Prognostic significance was analyzed using multivariate Cox regression.PGK1 was highly expressed in all gallbladder mucosa. Decreased PGK1 expression was detected in 54.7% (52/95) of patients with GBC. It was significantly down-regulated in GBC samples compared with that in gallbladder mucosa (P < 0.0001), and was associated with multiple clinicopathological factors. Multivariate survival analysis showed that low PGK1 expression was associated with shorter OS (median 12.8 vs 45.4 months; hazard ratio [HR] = 3.077; 95% confidence interval [CI], 1.373-6.897; P = 0.006) ...
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Traumatic brain injury (TBI) is a leading cause of death and disability. Previous studies have investigated the association of apolipoprotein E (APOE) ε4 with functional outcome after TBI and reported inconsistent results.The purpose of... more
Traumatic brain injury (TBI) is a leading cause of death and disability. Previous studies have investigated the association of apolipoprotein E (APOE) ε4 with functional outcome after TBI and reported inconsistent results.The purpose of this study was to perform a systematic literature search and conduct meta-analyses to examine whether APOE ε4 is associated with poorer functional outcome in patients with TBI.We performed a systematic literature search in PubMed, Cochrane Library, Embase, Google Scholar, and HuGE.The eligibility criteria of this study included the following: Patients had TBI; the studies reported APOE genotype data or provided odds ratios (ORs) and the corresponding 95% confidence intervals (CIs); the functional outcome was assessed using the Glasgow Outcome Scale (GOS) or the Glasgow Outcome Scale Extended (GOSE); and patients were followed for at least 3 months after TBI.In all meta-analyses, we used random-effects models to calculate the odds ratio as a measure o...
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DNA methylation plays a crucial role in the regulation of gene expression, cell differentiation and development. Previous studies have reported age-related alterations of methylation levels in the human brain across the lifespan, but... more
DNA methylation plays a crucial role in the regulation of gene expression, cell differentiation and development. Previous studies have reported age-related alterations of methylation levels in the human brain across the lifespan, but little is known about whether the observed association with age is confounded by common neuropathologies among older persons. Using genome-wide DNA methylation data from 740 postmortem brains, we interrogated 420,132 CpG sites across the genome in a cohort of individuals with ages from 66 to 108 years old, a range of ages at which many neuropathologic indices become quite common. We compared the association of DNA methylation prior to and following adjustment for common neuropathologies using a series of linear regression models. In the simplest model adjusting for technical factors including batch effect and bisulfite conversion rate, we found 8156 CpGs associated with age. The number of CpGs associated with age dropped by more than 10% following adjus...
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To examine the effects of genetic polymorphisms in cytochrome P450, subfamily 1, polypeptide 1 (C1P1B1) on primary open-angle glaucoma (POAG). A systematic literature search was performed, and random-effects meta-analyses were used to... more
To examine the effects of genetic polymorphisms in cytochrome P450, subfamily 1, polypeptide 1 (C1P1B1) on primary open-angle glaucoma (POAG). A systematic literature search was performed, and random-effects meta-analyses were used to evaluate genetic polymorphisms in CYP1B1 with POAG. A gene-based analysis was conducted to investigate the cumulative effects of genetic polymorphisms in CYP1B1. A total of six studies from published papers were included in our analysis. Random-effects meta-analyses failed to detect any significant association of POAG with genetic polymorphisms in CYP1B1, including rs180040, rs1056836, rs10012, rs1056827, rs1056837, and rs2567206. The gene-based analysis indicated that the cumulative effect of genetic polymorphisms in CYP1B1 is not associated with POAG (p>0.50). We did not find any evidence of strong association of POAG with CYP1B1 genetic polymorphisms and their cumulative effect.
Research Interests: Genetics, Biology, Medicine, Humans, Mutation, and 12 moreMeta Analysis, Aged, Middle Aged, Optometry and Ophthalmology, Adult, Genetic Polymorphism, European Continental Ancestry Group, Asian Continental Ancestry Group, Genetic Association, Case Control Studies, Primary Open Angle Glaucoma, and Databases Bibliographic
To test the hypothesis that physical activity modifies the association between white matter hyperintensity (WMH) burden and motor function in healthy older persons without dementia. Total daily activity (exercise and nonexercise physical... more
To test the hypothesis that physical activity modifies the association between white matter hyperintensity (WMH) burden and motor function in healthy older persons without dementia. Total daily activity (exercise and nonexercise physical activity) was measured for up to 11 days with actigraphy (Actical; Philips Respironics, Bend, OR) in 167 older adults without dementia participating in the Rush Memory and Aging Project. Eleven motor performances were summarized into a previously described global motor score. WMH volume was expressed as percent of intracranial volume. Linear regression models, adjusted for age, education, and sex, were performed with total WMH volume as the predictor and global motor score as the outcome. Terms for total daily physical activity and its interaction with WMH volume were then added to the model. Higher WMH burden was associated with lower motor function (p = 0.006), and total daily activity was positively associated with motor function (p = 0.002). Tot...
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The objective of this study is to investigate the effect of breastfeeding on childhood obesity in China.We used data collected from the China Family Panel Studies, an ongoing, prospective, and nationwide longitudinal study to explore the... more
The objective of this study is to investigate the effect of breastfeeding on childhood obesity in China.We used data collected from the China Family Panel Studies, an ongoing, prospective, and nationwide longitudinal study to explore the extensive and dynamic social changes in China. A total of 7967 children were included in the analysis. Duration of breastfeeding was first treated as a continuous variable and subsequently dichotomized into ever versus never, ≥6 months versus <6 months, ≥8 months versus < 8 months, and ≥12 months versus <12 months. Multiple imputation was conducted and regressions with propensity score matching were performed. We also performed quantile regression to examine whether breastfeeding has an effect on childhood obesity among children with a specific quantile of body mass index (BMI).Consistent with findings from recent studies, in both adjusted and adjusted regressions, we did not find any statistically significant effect of breastfeeding…
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Recent large-scale genome-wide association studies have discovered several genetic variants associated with Alzheimer disease (AD); however, the extent to which DNA methylation in these AD loci contributes to the disease susceptibility... more
Recent large-scale genome-wide association studies have discovered several genetic variants associated with Alzheimer disease (AD); however, the extent to which DNA methylation in these AD loci contributes to the disease susceptibility remains unknown. To examine the association of brain DNA methylation in 28 reported AD loci with AD pathologies. Ongoing community-based clinical pathological cohort studies of aging and dementia (the Religious Orders Study and the Rush Memory and Aging Project) among 740 autopsied participants 66.0 to 108.3 years old. DNA methylation levels at individual CpG sites generated from dorsolateral prefrontal cortex tissue using a bead assay. Pathological diagnosis of AD by National Institute on Aging-Reagan criteria following a standard postmortem examination. Overall, 447 participants (60.4%) met the criteria for pathological diagnosis of AD. Brain DNA methylation in SORL1, ABCA7, HLA-DRB5, SLC24A4, and BIN1 was associated with pathological AD. The associ...
Research Interests: Cognitive Science, Dementia, Biology, Medicine, Brain, and 15 moreHumans, Methylation, Female, Male, DNA methylation, CpG islands, Genetic Association Studies, Membrane transport proteins, Clinical Sciences, Aged, Alzheimer Disease, Neurosciences, Pathological, Cohort Studies, and Residence Characteristics
We hypothesized that circulating leukocyte RNA profiles or “riboleukograms” detect ventilator-associated pneumonia after blunt trauma. A pilot microarray study of 11 ventilator-associated pneumonia (VAP) patients suggested that 85... more
We hypothesized that circulating leukocyte RNA profiles or “riboleukograms” detect ventilator-associated pneumonia after blunt trauma. A pilot microarray study of 11 ventilator-associated pneumonia (VAP) patients suggested that 85 leukocyte genes can be used to diagnose VAP. Validation of this gene set to detect VAP was tested using data from an independent patient cohort. A total of 158 intubated blunt trauma patients were enrolled at 5 centers, where 57 (36%) developed VAP. Patient age was 34.2 ± 11.1 years; 65% were male. Circulating leukocyte GeneChip U133 2.0 expression values were measured at time 0.5, 1, 4, 7, 14, 21, and 28 days after injury. DChip normalized leukocyte transcriptional profiles were analyzed using repeated measures logistic regression. A compound covariate model based on leukocyte gene transcriptional profiles in a training subset of patients was tested to determine predictive accuracy for VAP 4 days prior to clinical diagnosis in the test subset. Using gene ...