| 1. |
- Wen, Wanqing, et al.
(författare)
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Genome-wide association studies in East Asians identify new loci for waist-hip ratio and waist circumference
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Sixty genetic loci associated with abdominal obesity, measured by waist circumference (WC) and waist-hip ratio (WHR), have been previously identified, primarily from studies conducted in Europeanancestry populations. We conducted a meta-analysis of associations of abdominal obesity with approximately 2.5 million single nucleotide polymorphisms (SNPs) among 53,052 (for WC) and 48,312 (for WHR) individuals of Asian descent, and replicated 33 selected SNPs among 3,762 to 17,110 additional individuals. We identified four novel loci near the EFEMP1, ADAMTSL3, CNPY2, and GNAS genes that were associated with WC after adjustment for body mass index (BMI); two loci near the NID2 and HLA-DRB5 genes associated with WHR after adjustment for BMI, and three loci near the CEP120, TSC22D2, and SLC22A2 genes associated with WC without adjustment for BMI. Functional enrichment analyses revealed enrichment of corticotropin-releasing hormone signaling, GNRH signaling, and/or CDK5 signaling pathways for those newly-identified loci. Our study provides additional insight on genetic contribution to abdominal obesity.
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| 2. |
- Wu, Jie, et al.
(författare)
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The impact of kidney function on plasma neurofilament light and phospho-tau 181 in a community-based cohort : the Shanghai Aging Study
- 2024
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Ingår i: Alzheimer's Research & Therapy. - : BioMed Central (BMC). - 1758-9193. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The blood-based biomarkers are approaching the clinical practice of Alzheimer's disease (AD). Chronic kidney disease (CKD) has a potential confounding effect on peripheral protein levels. It is essential to characterize the impact of renal function on AD markers.METHODS: Plasma phospho-tau181 (P-tau181), and neurofilament light (NfL) were assayed via the Simoa HD-X platform in 1189 dementia-free participants from the Shanghai Aging Study (SAS). The estimated glomerular filter rate (eGFR) was calculated. The association between renal function and blood NfL, P-tau181 was analyzed. An analysis of interactions between various demographic and comorbid factors and eGFR was conducted.RESULTS: The eGFR levels were negatively associated with plasma concentrations of NfL and P-tau181 (B = - 0.19, 95% CI - 0.224 to - 0.156, P < 0.001; B = - 0.009, 95% CI - 0.013 to -0.005, P < 0.001, respectively). After adjusting for demographic characteristics and comorbid diseases, eGFR remained significantly correlated with plasma NfL (B = - 0.010, 95% CI - 0.133 to - 0.068, P < 0.001), but not with P-tau181 (B = - 0.003, 95% CI - 0.007 to 0.001, P = 0.194). A significant interaction between age and eGFR was found for plasma NfL (Pinteraction < 0.001). In participants ≥ 70 years and with eGFR < 60 ml/min/1.73 m2, the correlation between eGFR and plasma NfL was significantly remarkable (B = - 0.790, 95% CI - 1.026 to - 0,554, P < 0.001).CONCLUSIONS: Considering renal function and age is crucial when interpreting AD biomarkers in the general aging population.
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| 3. |
- Xiao, Zhenxu, et al.
(författare)
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Olfactory function, neurofilament light chain, and cognitive trajectory : A 12-year follow-up of the Shanghai Aging Study
- 2023
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Ingår i: Alzheimer's and Dementia. - : John Wiley & Sons. - 2352-8729. ; 15:4
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to determine whether blood neurofilament light chain (NfL) modifies the association of olfactory dysfunction (OD) with long-term cognitive decline. A total of 1125 non-demented older adults in the Shanghai Aging Study were evaluated for baseline olfaction (12-item Sniffin' Sticks Smell Test) and cognitive trajectory by a 12-year follow-up. Baseline blood NfL was quantified using Single Molecular Array assay, and dichotomized into low and high levels based on the median value of concentration. The Mini-Mental State Examination (MMSE) and Telephone Interview for Cognitive Status-40 were used to assess participants' cognitive function. Cognitive decline was ascertained when dementia was diagnosed or documented in the medical record during follow-up, or the MMSE declining rate (slope) was 1.0 SD larger than the group mean. OD participants presented a steeper trajectory of MMSE score (p interaction = 0.004) and a high risk of cognitive decline (adjusted HR [95% CI], 1.82 [1.11, 2.98]) only in those with high NfL. Participants with combined OD and high NfL showed the highest risk of cognitive decline (adjusted HR, 2.43 [1.20, 4.92]). OD, especially in combination with high blood NfL concentration, may be able to identify individuals who later incur cognitive deterioration.
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| 4. |
- Xiao, Zhenxu, et al.
(författare)
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Plasma p-tau217, p-tau181, and NfL as early indicators of dementia risk in a community cohort : The Shanghai Aging Study
- 2023
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Ingår i: Alzheimer's and Dementia. - : John Wiley & Sons. - 2352-8729. ; 15:4
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Blood biomarkers showed values for predicting future cognitive impairment. Evidence from the community-based cohort was limited only in high-income countries.METHODS: This study included 1857 dementia-free community residents recruited in 2009-2011 and followed up in waves 2014-2016 and 2019-2023 in the Shanghai Aging Study. We intended to explore the relationships of baseline plasma ALZpath phosphorylated tau 217 (p-tau217), p-tau181, neurofilament light chain (NfL) with follow-up incident dementia, Alzheimer's disease (AD), and amyloidosis.RESULTS: Higher concentrations of plasma p-tau217, p-tau181, and NfL were correlated to higher decline speed of Mini-Mental State Examination score, and higher risk of incident dementia and AD. The p-tau217 demonstrated a significant correlation with longitudinal neocortical amyloid-beta (Aβ) deposition (r = 0.57 [0.30, 0.76]) and a high accuracy differentiating Aβ+ from Aβ- at follow-ups (area under the receiver operating characteristic curve = 0.821 [0.703, 0.940]).DISCUSSION: Plasma p-tau217 may be an early predictive marker of AD and Aβ pathology in older community-dwelling individuals.Highlights: Plasma p-tau217, p-tau181, and NfL were positively associated with long-term cognitive decline and risk of incident dementia.Plasma p-tau217 showed a better performance distinguishing Aβ+ individuals from Aβ- individuals at follow-ups.Plasma NfL may be a suitable predictor of general cognitive decline in older community-dwelling individuals.
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| 5. |
- Cao, Yang, Associate Professor, 1972-, et al.
(författare)
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Is Olfactory Impairment Associated With 10-year Mortality Mediating by Neurodegenerative Diseases in Older Adults? The Four-Way Decomposition Analysis
- 2021
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Ingår i: Frontiers In Public Health. - : Frontiers Media S.A.. - 2296-2565. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Literature shows that olfactory impairment (OI) is associated not only with neurodegenerative diseases (NDDs), but also with increased mortality. In this study, we analyzed data collected from the prospective phase of the 10-year follow-up of the Shanghai Aging Study (SAS) to explore the mediation effect of NDDs on the OI-mortality relationship.Methods: We analyzed data collected from the prospective phase of the 10-year follow-up of the SAS. We included 1,811 participants aged 60 years or older who completed both an olfactory identification test and a cognitive assessment at baseline (2010-2011). Survival status of the participants from baseline to December 31, 2019 was obtained from the local mortality surveillance system. We used the four-way decomposition method to attribute effects to interaction and mediation and to explore the mediation effect of NDDs on the OI-mortality relationship.Results: The four-way decomposition method revealed a statistically significant association of OI with death. Overall, 43% higher risk for death was associated with OI [excess relative risk (ERR) = 0.43, 95% CI: 0.06-0.80, p = 0.023]. Excluding the mediation from NDDs and interaction between OI and NDDs, the controlled direct effect of OI on death was even higher in NDDs participants, with an ERR of 77% (95% CI: 0.00-1.55, p = 0.050). Statistically significant association was found for failure to identify coffee (ERR = 0.77, 95% CI: 0.18-1.36, p = 0.010) and marginally significant associations were found for failure to identify cinnamon (ERR = 0.33, 95% CI: -0.02-0.68, p = 0.068) and rose (ERR = 0.33, 95% CI: -0.01-0.67, p = 0.054) with death.Conclusion: OI was associated with the long-term mortality in older adults and the association was even stronger in those with NDDs. Failure to identify coffee or rose was associated with a higher mortality risk, and the association was mediated by NDDs.
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| 6. |
- Chen, Zhishan, et al.
(författare)
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Fine-mapping analysis including over 254 000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes
- 2024
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.
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| 7. |
- de las Fuentes, Lisa, et al.
(författare)
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Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci
- 2021
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Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 26:6, s. 2111-2125
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Tidskriftsartikel (refereegranskat)abstract
- Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, “Some College” (yes/no) and “Graduated College” (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
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| 8. |
- Ding, Ding, et al.
(författare)
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Can dementia be predicted using olfactory identification test in the elderly? A Bayesian network analysis
- 2020
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Ingår i: Brain and Behavior. - : John Wiley & Sons. - 2162-3279 .- 2162-3279. ; 10:11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Previous studies suggest that olfactory dysfunction is associated with cognitive decline or dementia.OBJECTIVE: To find a potential association between the olfactory identification (OI) and dementia onset, and build a prediction model for dementia screening in the older population.METHODS: Nine hundred and forty-seven participants from the Shanghai Aging Study were analyzed. The participants were dementia-free and completed OI test using the Sniffin' Sticks Screening Test-12 at baseline. After an average of 4.9-year follow-up, 75 (8%) of the participants were diagnosed with incident dementia. Discrete Bayesian network (DBN) and multivariable logistic regression (MLR) models were used to explore the dependencies of the incident dementia on the baseline demographics, lifestyles, and OI test results.RESULTS: In DBN analysis, odors of orange, cinnamon, peppermint, and pineapple, combined with age and Mini-mental State Examination (MMSE), achieved a high predictive ability for incident dementia, with an area under the receiver operating characteristic curve (AUC) larger than 0.8. The odor cinnamon showed the highest AUC of 0.838 (95% CI: 0.731-0.946) and a high accuracy of 0.867. The DBN incorporating age, MMSE, and one odor test had an accuracy (0.760-0.872 vs. 0.835) comparable to that of the MLR model and revealed the dependency between the variables.CONCLUSION: The DBN using OI test may have predictive ability comparable to MLR analysis and suggest potential causal relationship for further investigation. Identification of odor cinnamon might be a useful indicator for dementia screening and deserve further investigation.
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| 9. |
- Ding, Ding, et al.
(författare)
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Cholesterol profiles and incident cognitive decline among older adults : the Shanghai Aging Study
- 2021
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Ingår i: Age and Ageing. - : Oxford University Press. - 0002-0729 .- 1468-2834. ; 50:2, s. 472-479
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: the association between cholesterol profiles and risk of cognitive decline among older adults was inconclusive.OBJECTIVE: to examine the association between cholesterol profiles and risk of cognitive decline in older adults with or without vascular risk factors (VRFs) in the prospective phase of the Shanghai Aging Study.DESIGN: a prospective community-based cohort study.SETTING: Shanghai, China.PARTICIPANTS: we prospectively followed 1,556 dementia-free participants aged ≥60 years with a baseline cholesterol profile for 5.2 years on average. Participants with at least one of obesity, diabetes, hypertension, stroke, and coronary artery disease were categorised to the VRFs group, and those free of any VRFs were categorised to the non-VRFs group.METHODS: total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol in serum were measured at baseline. At follow-up, consensus diagnosis of incident dementia and Alzheimer's disease (AD) were established based on medical, neurological, and neuropsychological examinations. Cox regression was used to assess the association between cholesterol and incident dementia/AD; multivariate linear regression was used to examine the relationship between cholesterol and an annual rate of Mini Mental State Examination (MMSE) score decline in participants with or without VRFs.RESULTS: among VRFs-free participants, TC (HR 0.62, 95%CI 0.40-0.95) and LDL-C (HR 0.47, 95%CI 0.28-0.80) were inversely associated with incident dementia, LDL-C was inversely associated with incident AD (HR 0.50, 95%CI 0.28-0.90). A significant correlation was found between incremental TC (β = 0.08), LDL-C (β = 0.09), and a slower annual decline of MMSE score.CONCLUSIONS: effect of cholesterol on cognitive decline may be modified by VRFs.
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| 10. |
- Ding, Ding, et al.
(författare)
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Predictive Value of Odor Identification for Incident Dementia : The Shanghai Aging Study
- 2020
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Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media S.A.. - 1663-4365 .- 1663-4365. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study aimed to evaluate the value of odors in the olfactory identification (OI) test and other known risk factors for predicting incident dementia in the prospective Shanghai Aging Study.Methods: At baseline, OI was assessed using the Sniffin' Sticks Screening Test 12, which contains 12 different odors. Cognition assessment and consensus diagnosis were conducted at both baseline and follow-up to identify incident dementia. Four different multivariable logistic regression (MLR) models were used for predicting incident dementia. In the no-odor model, only demographics, lifestyle, and medical history variables were included. In the single-odor model, we further added one single odor to the first model. In the full model, all 12 odors were included. In the stepwise model, the variables were selected using a bidirectional stepwise selection method. The predictive abilities of these models were evaluated by the area under the receiver operating characteristic curve (AUC). The permutation importance method was used to evaluate the relative importance of different odors and other known risk factors.Results: Seventy-five (8%) incident dementia cases were diagnosed during 4.9 years of follow-up among 947 participants. The full and the stepwise MLR model (AUC = 0.916 and 0.914, respectively) have better predictive abilities compared with those of the no- or single-odor models. The five most important variables are Mini-Mental State Examination (MMSE) score, age, peppermint detection, coronary artery disease, and height in the full model, and MMSE, age, peppermint detection, stroke, and education in the stepwise model. The combination of only the top five variables in the stepwise model (AUC = 0.901 and sensitivity = 0.880) has as a good a predictive ability as other models.Conclusion: The ability to smell peppermint might be one of the useful indicators for predicting dementia. Combining peppermint detection with MMSE, age, education, and history of stroke may have sensitive and robust predictive value for dementia in older adults.
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