| 1. |
- 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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| 2. |
- Li, Xiaochun, et al.
(författare)
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Bidirectional associations of intellectual and social activities with cognitive function among middle-aged and elderly adults in China
- 2022
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Ingår i: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327. ; 319, s. 83-89
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous studies evaluating the association between leisure activities and cognitive function produced conflicting results. Different types of leisure activities may have different effects on cognition, and very few studies have explored their bidirectional associations. Our study aimed to explore whether intellectual and social activities had bidirectional associations with cognitive function among the middle-aged and elderly adults in China. Methods: Data was derived from the China Health and Retirement Longitudinal Study. The data in this study were based on 11,549 participants aged 45 or older whose intellectual and social activities and cognitive function were assessed at baseline. Cross-lagged panel model was used to examine the temporal relationship of intellectual and social activities with cognitive function. Results: Totally, 5624 participants completed the third follow-up in 2018. The results showed that the better the cognitive function they had at baseline, the more intellectual activities they were engage in (β = 0.044, P < 0.001) and vice versa (β = 0.042, P = 0.001). Additionally, better cognitive function at baseline was significantly associated with more engagement in social activities (β = 0.028, P = 0.030); in contrast, higher engagement in social activities at baseline was not related to better cognitive function (β = −0.008, P = 0.523). Limitations: Engagement in social and intellectual activities was assessed via questionnaire. Conclusions: Our findings indicated that there was a bidirectional relationship between intellectual activities and cognitive function. However, participation in social activities did not slow down the decline in cognitive function. Participating in intellectual activities, compared to social activities, is especially beneficial for cognitive function.
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| 3. |
- Chen, Xuan, et al.
(författare)
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Prevalence of Abdominal Obesity in Chinese Middle-Aged and Older Adults with a Normal Body Mass Index and Its Association with Type 2 Diabetes Mellitus : A Nationally Representative Cohort Study from 2011 to 2018
- 2021
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Ingår i: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. - 1178-7007. ; 14, s. 4829-4841
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Tidskriftsartikel (refereegranskat)abstract
- Background: Few studies have focused on the prevalence of abdominal obesity in Chinese middle-aged and older adults with a normal body mass index (BMI). Furthermore, it is still unclear whether abdominal obesity is an independent risk factor for type 2 diabetes mellitus (T2DM). Participants with a normal BMI are usually neglected during assessments of abdominal obesity-associated T2DM risk since the current recommendations for medical interventions are mainly focused on overall body mass index rather than fat deposition patterns. Methods: In this study, 7942 normal-BMI participants aged over 45 years from the China Health and Retirement Longitudinal Study were included to assess the prevalence of abdominal obesity defined by waist circumference (WC) or waist-to-height ratio (WHtR). In addition, 4348 normal-BMI individuals with no diabetes at baseline were included to evaluate the association between abdominal obesity and the risk of T2DM with the Cox proportional hazards model. Results: The prevalence (95% confidence interval, CI) of increased WC and substantially increased WC among adults with a normal BMI was 22.0% (21.1%-22.9%) and 18.1% (17.3%-19.0%), respectively. The adjusted hazard ratios and 95% CIs for T2DM incidence were 1.39 (1.05–1.85) and 1.89 (1.42–2.53) for those with increased WC and substantially increased WC, respectively, compared to the individuals with a normal WC. Similar HRs were obtained for the association between WHtR and the risk of T2DM. In prediabetic patients, the HRs (95% CIs) for new-onset T2DM for those with increased WC and substantially increased WC were 1.85 (1.27–2.69) and 2.46 (1.67–3.61), respectively, when compared with individuals with normal WC. This positive association was observed in women but not in men or adults with normal glucose tolerance (NGT). Conclusion: Abdominal obesity is highly prevalent among middle-aged and older Chinese adults with a normal BMI, and maintaining a normal waist circumference may be beneficial in the prevention of T2DM.
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| 4. |
- de Vries, Paul S., et al.
(författare)
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Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
- 2019
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Ingår i: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 188:6, s. 1033-1054
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Tidskriftsartikel (refereegranskat)abstract
- A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.
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| 5. |
- Feitosa, Mary F., et al.
(författare)
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Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries
- 2018
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Ingår i: PLOS ONE. - : Public library science. - 1932-6203. ; 13:6
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Tidskriftsartikel (refereegranskat)abstract
- Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in approximate to 131 K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P <1.0 x 10(-5)). In Stage 2, these SNVs were tested for independent external replication in individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10(-8)). For African ancestry samples, we detected 18 potentially novel BP loci (P< 5.0 x 10(-8)) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2 have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
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| 6. |
- Li, Ning, et al.
(författare)
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Associations of genetically determined lipid traits and lipid-modifying agents with the risk of diabetic retinopathy : A Mendelian randomization study
- 2023
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Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 369, s. 9-16
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: The evidence that dyslipidemia is associated with hyperglycemia calls for an investigation of whether dyslipidemia, as well as lipid-modifying agents, could affect the subsequent development of diabetic retinopathy (DR). Therefore, we aimed to address these unanswered questions by utilizing Mendelian randomization (MR) analysis.METHODS: Genetic variants were selected from the UK Biobank as instruments to serve as proxies for lipid traits [high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), apolipoprotein A-I (APOA-I) and apolipoprotein B (APOB)]. Univariable and multivariable MR analyses were performed to examine the associations of these lipid traits with DR and different levels of severity of DR. Based on the evidence for the effects of lipids on outcomes, we estimated the causal relevance of cholesteryl ester transfer protein (CETP) inhibitors in severe nonproliferative and proliferative DR using protein quantitative trait loci (pQTLs) and expression quantitative trait loci (eQTLs) as instruments.RESULTS: Genetically determined HDL-C levels were inversely associated with the risk of severe nonproliferative DR (OR = 0.70, 95% CI = 0.52-0.94) and proliferative DR (OR = 0.90, 95% CI = 0.83-0.97) in the main analyses utilizing the inverse variance-weighted (IVW) MR method and a couple of sensitivity analyses. No association was noted between genetically proxied CETP inhibitors and DR.CONCLUSIONS: This MR study suggests the casual protective roles of HDL-C in severe nonproliferative DR and proliferative DR, which calls for further studies to confirm these findings. Current lipid-modifying agents acting on HDL-C may not reduce the risk of DR and new treatments are required in the future.
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| 7. |
- Sung, Yun Ju, et al.
(författare)
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A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure
- 2019
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 28:15, s. 2615-2633
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Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P < 5 × 10−8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.
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| 8. |
- Zheng, Manqi, et al.
(författare)
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Development and validation of risk prediction models for new-onset type 2 diabetes in adults with impaired fasting glucose
- 2023
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Ingår i: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227. ; 197
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To develop and validate sex-specific risk prediction models based on easily obtainable clinical data for predicting 5-year risk of type 2 diabetes (T2D) among individuals with impaired fasting glucose (IFG), and generate practical tools for public use. Methods: The data used for model training and internal validation came from a large prospective cohort (N = 18,384). Two independent cohorts were used for external validation. A two-step approach was applied to screen variables. Coefficient-based models were constructed by multivariate Cox regression analyses, and score-based models were subsequently generated. The predictive power was evaluated by the area under the curve (AUC). Results: During a median follow-up of 7.55 years, 5697 new-onset T2D cases were identified. Predictor variables included age, body mass index, waist circumference, diastolic blood pressure, triglycerides, fasting plasma glucose, and fatty liver. The proposed models outperformed five existing models. In internal validation, the AUCs of the coefficient-based models were 0.741 (95% CI 0.723–0.760) for men and 0.762 (95% CI 0.720–0.802) for women. External validation yielded comparable prediction performance. We finally constructed a risk scoring system and a web calculator. Conclusions: The risk prediction models and derived tools had well-validated performance to predict the 5-year risk of T2D in IFG adults.
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