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Article ; Online: Causal influence of sleeping phenotypes on the risk of coronary artery disease and sudden cardiac arrest: A Mendelian randomization analysis.

Chiu, Yen-Wei / Su, Mei-Hsin / Lin, Yen-Feng / Chen, Chia-Yen / Chen, Tzu-Ting / Wang, Shi-Heng

2023 Volume 9, Issue 5, Page(s) 726–732

Abstract: Objectives: To assess the causal influence of sleep and circadian traits on coronary artery disease and sudden cardiac arrest with adjustment for obesity through a two-sample Mendelian randomization study.: Methods: We used summary statistics of 5 ... ...

Abstract	Objectives: To assess the causal influence of sleep and circadian traits on coronary artery disease and sudden cardiac arrest with adjustment for obesity through a two-sample Mendelian randomization study. Methods: We used summary statistics of 5 sleep and circadian traits for genome-wide association studies, including chronotype, sleep duration, long sleep (≥9 h a day), short sleep (<7 h a day), and insomnia (sample size range: 237,622-651,295). Coronary artery disease genome-wide association studies with 60,801 cases and 123,504 controls, sudden cardiac arrest genome-wide association studies with 3939 cases and 25,989 controls, and obesity genome-wide association studies with 806,834 individuals were also used. Multivariable Mendelian randomization was performed to estimate the causality. Results: After adjusting for obesity, genetically predicted short sleep (odds ratio = 1.87 and p = .02), and genetically predicted insomnia (odds ratio = 1.17 and p = .001) were causally associated with increased odds of coronary artery disease. Genetically predicted long sleep (odds ratio = 0.06 and p = .02) and genetically predicted longer sleep duration (odds ratio = 0.36 for per-hour increase in sleep duration and p = .0006) were causally associated with decreased odds of sudden cardiac arrest. Conclusions: The findings of this Mendelian randomization study indicate that insomnia and short sleep contribute to the development of coronary artery disease, whereas a longer sleep duration protects from sudden cardiac arrest, independent of the influence of obesity. The mechanisms underlying these associations warrant further investigation.
Language	English
Publishing date	2023-07-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2813299-3
ISSN	2352-7226 ; 2352-7218
ISSN (online)	2352-7226
ISSN	2352-7218
DOI	10.1016/j.sleh.2023.05.009
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Article ; Online: Causal influence of dietary habits on the risk of major depressive disorder: A diet-wide Mendelian randomization analysis.

Chen, Tzu-Ting / Chen, Chia-Yen / Fang, Chiu-Ping / Cheng, Ying-Chih / Lin, Yen-Feng

Journal of affective disorders

2022 Volume 319, Page(s) 482–489

Abstract: Background: Extensive observational evidence links diet quality to the risk for major depressive disorder (MDD), while clinical trials show that dietary improvement can improve depressive symptoms. However, due to issues with blinding dietary trials, ... ...

Abstract	Background: Extensive observational evidence links diet quality to the risk for major depressive disorder (MDD), while clinical trials show that dietary improvement can improve depressive symptoms. However, due to issues with blinding dietary trials, confirming a causal relationship for diet's influence on MDD requires further research. Thus, we systemically investigated the bi-directional causal relationships between dietary habits and MDD by using two-sample Mendelian randomization (MR). Methods: We collected publicly available genome-wide association studies' summary statistics for dietary habits from UK Biobank (n = 449,210) and MDD from the Psychiatric Genomics Consortium (n = 142,646). We used a weighted median approach to synthesize MR estimates across genetic instruments. For the robustness of our results, we compared weighted median results with results from the inverse-variance weighted, the weighted mode, and MR-PRESSO. Results: There was moderate evidence that beef intake has a protective effect on MDD. There was weak but detectable evidence that cereal intake has a protective effect on MDD, while non-oily fish intake might increase the risk of MDD. We did not observe any causal effect of MDD on dietary habits. Limitations: Our study may suffer from the violation of assumptions of MR due to horizontal pleiotropy; therefore, we did several sensitivity analyses to detect and minimize the bias. Conclusions: In this two-sample MR analysis, we observed that higher beef intake may be protective against MDD. However, MDD did not appear to affect dietary habits. Potential mechanisms need to be further investigated to support our novel findings.
MeSH term(s)	Humans ; Mendelian Randomization Analysis ; Depressive Disorder, Major/genetics ; Genome-Wide Association Study ; Feeding Behavior ; Diet ; Polymorphism, Single Nucleotide
Language	English
Publishing date	2022-09-23
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	135449-8
ISSN	1573-2517 ; 0165-0327
ISSN (online)	1573-2517
ISSN	0165-0327
DOI	10.1016/j.jad.2022.09.109
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Article ; Online: General retrospective mega-analysis framework for rare variant association tests.

Chien, Li-Chu / Chiu, Yen-Feng

Genetic epidemiology

2018 Volume 42, Issue 7, Page(s) 621–635

Abstract: Here, we describe a retrospective mega-analysis framework for gene- or region-based multimarker rare variant association tests. Our proposed mega-analysis association tests allow investigators to combine longitudinal and cross-sectional family- and/or ... ...

Abstract	Here, we describe a retrospective mega-analysis framework for gene- or region-based multimarker rare variant association tests. Our proposed mega-analysis association tests allow investigators to combine longitudinal and cross-sectional family- and/or population-based studies. This framework can be applied to a continuous, categorical, or survival trait. In addition to autosomal variants, the tests can be applied to conduct mega-analyses on X-chromosome variants. Tests were built on study-specific region- or gene-level quasiscore statistics and, therefore, do not require estimates of effects of individual rare variants. We used the generalized estimating equation approach to account for complex multiple correlation structures between family members, repeated measurements, and genetic markers. While accounting for multilevel correlations and heterogeneity across studies, the test statistics were computationally efficient and feasible for large-scale sequencing studies. The retrospective aspect of association tests helps alleviate bias due to phenotype-related sampling and type I errors due to misspecification of phenotypic distribution. We evaluated our developed mega-analysis methods through comprehensive simulations with varying sample sizes, covariates, population stratification structures, and study designs across multiple studies. To illustrate application of the proposed framework, we conducted a mega-association analysis combining a longitudinal family study and a cross-sectional case-control study from Genetic Analysis Workshop 19.
MeSH term(s)	Algorithms ; Case-Control Studies ; Computer Simulation ; Cross-Sectional Studies ; Genetic Association Studies ; Genetic Variation ; Humans ; Hypertension/genetics ; Models, Genetic ; Numerical Analysis, Computer-Assisted ; Phenotype ; Retrospective Studies ; Risk Factors
Language	English
Publishing date	2018-09-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	605785-8
ISSN	1098-2272 ; 0741-0395
ISSN (online)	1098-2272
ISSN	0741-0395
DOI	10.1002/gepi.22147
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Article ; Online: Shared genetic architectures of educational attainment in East Asian and European populations.

Nature human behaviour

2024 Volume 8, Issue 3, Page(s) 562–575

Abstract: Educational attainment (EduYears), a heritable trait often used as a proxy for cognitive ability, is associated with various health and social outcomes. Previous genome-wide association studies (GWASs) on EduYears have been focused on samples of European ...

Abstract	Educational attainment (EduYears), a heritable trait often used as a proxy for cognitive ability, is associated with various health and social outcomes. Previous genome-wide association studies (GWASs) on EduYears have been focused on samples of European (EUR) genetic ancestries. Here we present the first large-scale GWAS of EduYears in people of East Asian (EAS) ancestry (n = 176,400) and conduct a cross-ancestry meta-analysis with EduYears GWAS in people of EUR ancestry (n = 766,345). EduYears showed a high genetic correlation and power-adjusted transferability ratio between EAS and EUR. We also found similar functional enrichment, gene expression enrichment and cross-trait genetic correlations between two populations. Cross-ancestry fine-mapping identified refined credible sets with a higher posterior inclusion probability than single population fine-mapping. Polygenic prediction analysis in four independent EAS and EUR cohorts demonstrated transferability between populations. Our study supports the need for further research on diverse ancestries to increase our understanding of the genetic basis of educational attainment.
MeSH term(s)	Humans ; East Asian People ; Genome-Wide Association Study ; Educational Status ; Academic Success ; Multifactorial Inheritance/genetics
Language	English
Publishing date	2024-01-05
Publishing country	England
Document type	Meta-Analysis ; Journal Article
ISSN	2397-3374
ISSN (online)	2397-3374
DOI	10.1038/s41562-023-01781-9
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Article ; Online: Interactions of Insomnia and Sedative-Hypnotic Drug Use Associated with Frailty Over Time Among Older Adults.

Wu, Chi-Shin / Tseng, Han-Yun / Lee, Chun-Yi / Wu, I-Chien / Chang, Hsing-Yi / Hsu, Chih-Cheng / Hsiung, Chao Agnes / Chiu, Yen-Feng

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry

2023 Volume 31, Issue 6, Page(s) 438–448

Abstract: Background: Insomnia and frailty are prevalent in older adults. This study aimed to elucidate the impact of insomnia and sedative-hypnotic use on the frailty rate over time.: Methods: We used data from community-dwelling older adults (mean ± SD age = ...

Abstract	Background: Insomnia and frailty are prevalent in older adults. This study aimed to elucidate the impact of insomnia and sedative-hypnotic use on the frailty rate over time. Methods: We used data from community-dwelling older adults (mean ± SD age = 69.4 ± 8.2 years) from the Healthy Aging Longitudinal Study in Taiwan (HALST). A total of 4,744 participants were included in the study and were followed up for an average of 3.2 years. Frailty was assessed using the Fried criteria. Self-reported sleep problems, sedative-hypnotic use, and claims records from the National Health Insurance database were used. The generalized equation estimation (GEE) approach was applied to account for correlations between repeated measures. The average impact of insomnia and drug use on frailty over time was estimated by adjusting for potential confounding factors using the logic link in the GEE approach. Results: The adjusted odds ratio (OR) of frailty was 1.41 (95% CI: [1.16, 1.72], Z-test statistics Z = 3.39, p <0.001) for insomnia and 1.52 ([1.16, 2.00], Z = 3.00, p = 0.0027) for sedative-hypnotic use. Interactions between insomnia and sedative-hypnotic use with frailty were not statistically significant. Long sleep duration > 8 hours, daytime sleepiness, and sleep apnea was also associated with an increased likelihood of developing frailty. Notably, a dose-response relationship between sedative-hypnotic drug use and frailty was observed. Conclusions: Insomnia and sedative-hypnotic use were independently associated with increased frailty. The implementation of nonpharmacological treatments to attenuate insomnia may reduce frailty rates.
MeSH term(s)	Humans ; Aged ; Sleep Initiation and Maintenance Disorders/drug therapy ; Sleep Initiation and Maintenance Disorders/epidemiology ; Frailty/epidemiology ; Longitudinal Studies ; Hypnotics and Sedatives/adverse effects ; Sleep
Chemical Substances	Hypnotics and Sedatives
Language	English
Publishing date	2023-02-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1278145-9
ISSN	1545-7214 ; 1064-7481
ISSN (online)	1545-7214
ISSN	1064-7481
DOI	10.1016/j.jagp.2023.01.028
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Zs.A 4443: Show issues

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Article: Assessment of fenofibrate-methylation interactions on triglycerides using longitudinal family data.

Yu, Jih-Chang / Hsu, Fang-Chi / Chiu, Yen-Feng

BMC proceedings

2018 Volume 12, Issue Suppl 9, Page(s) 48

Abstract: Background: Triglyceride (TG) concentrations decrease in response to fenofibrate treatment, and also are associated with DNA methylation. But how interactions between fenofibrate response and DNA methylation affect TGs remains unclear.: Methods: In ... ...

Abstract	Background: Triglyceride (TG) concentrations decrease in response to fenofibrate treatment, and also are associated with DNA methylation. But how interactions between fenofibrate response and DNA methylation affect TGs remains unclear. Methods: In the present study, we identified and compared differential methylation sites associated with TG concentrations in individuals before and after fenofibrate treatment. We then estimated interactions between fenofibrate treatment and methylation to identify differential methylation effects associated with fenofibrate treatment on TG concentrations using the entire longitudinal family sample. To account for within-family and within-individual corrections, the generalized estimating equations approach was used to estimate main and interaction effects between methylation sites and fenofibrate treatment, adjusting for potential confounders. Analyses were also performed with and without adjusting for high-density lipoprotein (HDL) concentrations. Results: Prior to fenofibrate treatment, 23 cytosine-phosphate-guanine (CpG) sites were significantly associated with TG concentrations, while only 13 CpG sites were identified posttreatment, adjusting for HDL. Without adjusting for HDL, pretreatment, 20 CpG sites were significantly associated with TG concentrations, while only 12 CpG sites were identified posttreatment. Among these sites, only one differential site (cg19003390 in the Conclusions: Our analyses suggest that DNA methylation likely modified the effect of fenofibrate on TG concentrations. Differential fenofibrate-associated methylation sites on TGs differed with and without adjusting for HDL concentrations, suggesting that these HDLs and TGs might share some common epigenetic processes.
Language	English
Publishing date	2018-09-17
Publishing country	England
Document type	Journal Article
ZDB-ID	2411867-9
ISSN	1753-6561
ISSN	1753-6561
DOI	10.1186/s12919-018-0132-y
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Article ; Online: Dietary Inflammatory Patterns Are Associated With Serum TGs and Insulin in Adults: A Community-Based Study in Taiwan.

Chuang, Shu-Chun / Wu, I-Chien / Hsiung, Chao Agnes / Chan, Huei-Ting / Cheng, Chiu-Wen / Chen, Hui-Ling / Chiu, Yen-Feng / Lee, Marion M / Chang, Hsing-Yi / Hsu, Chih-Cheng

The Journal of nutrition

2023 Volume 153, Issue 6, Page(s) 1783–1792

Abstract: Background: Dietary patterns related to inflammation have become a focus of disease prevention but the patterns may vary among populations.: Objectives: The study was conducted to determine Taiwanese dietary inflammatory patterns and evaluate their ... ...

Abstract	Background: Dietary patterns related to inflammation have become a focus of disease prevention but the patterns may vary among populations. Objectives: The study was conducted to determine Taiwanese dietary inflammatory patterns and evaluate their associations with biomarkers of lipid and glucose. Methods: Data were taken from 5664 community-dwelling individuals aged ≥55 y recruited in 2009-2013 in the Healthy Aging Longitudinal Study in Taiwan (HALST). Dietary data were obtained from an FFQ. An empirical dietary inflammatory pattern (EDIP) was derived from reduced rank regression models that explained the serum high-sensitivity CRP, plasma IL-6, and TNF receptor 1. Cross-sectional associations between dietary scores and biomarkers of total cholesterol (TC); HDL cholesterol; LDL cholesterol; TG; and ratios of TG/HDL cholesterol, TG/TC, fasting glucose, insulin, and HbA1c were analyzed via multiple linear regression and adjusted for major confounders. The false-discovery rate (FDR)-adjusted P < 0.05 was considered statistically significant. Abdominal obesity was defined as a waist circumference of ≥90 cm for men and ≥80 cm for women. Results: Higher EDIP-HALST scores were associated with higher TG (per score increment: 1.62%, 95% CI: 0.58%, 2.76%; P Conclusions: Inflammatory diets, as measured via EDIP-HALST, are associated with serum TG concentration, particularly in participants with abdominal obesity. These findings may suggest that developing disease prevention strategies using dietary inflammatory patterns may be different by populations. J Nutr 20xx;x:xx.
MeSH term(s)	Male ; Humans ; Adult ; Female ; Insulin ; Cholesterol, HDL ; Longitudinal Studies ; Obesity, Abdominal ; Taiwan ; Cross-Sectional Studies ; Obesity ; Insulin, Regular, Human ; Biomarkers ; Glucose ; Triglycerides
Chemical Substances	Insulin ; Cholesterol, HDL ; Insulin, Regular, Human ; Biomarkers ; Glucose (IY9XDZ35W2) ; Triglycerides
Language	English
Publishing date	2023-04-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218373-0
ISSN	1541-6100 ; 0022-3166
ISSN (online)	1541-6100
ISSN	0022-3166
DOI	10.1016/j.tjnut.2023.04.015
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Article ; Online: Carbohydrate Antigen 19-9 Response to Initial Adjuvant Chemotherapy Predicts Survival and Failure Pattern of Resected Pancreatic Adenocarcinoma but Not Which Patients Are Suited for Additional Adjuvant Chemoradiation Therapy: From a Prospective Randomized Study.

Chiu, Yen-Feng / Liu, Tsang-Wu / Shan, Yan-Shen / Chen, Jen-Shi / Li, Chung-Pin / Ho, Ching-Liang / Hsieh, Ruey-Kuen / Hwang, Tsann-Long / Chen, Li-Tzong / Ch'ang, Hui-Ju

International journal of radiation oncology, biology, physics

2023 Volume 117, Issue 1, Page(s) 74–86

Abstract: Purpose: The predictive value of carbohydrate antigen 19-9 (CA19-9) for adjuvant chemo(radiation) therapy of resected pancreatic adenocarcinoma (PDAC) is undefined.: Methods and materials: We analyzed CA19-9 levels in patients with resected PDAC in a ...

Abstract	Purpose: The predictive value of carbohydrate antigen 19-9 (CA19-9) for adjuvant chemo(radiation) therapy of resected pancreatic adenocarcinoma (PDAC) is undefined. Methods and materials: We analyzed CA19-9 levels in patients with resected PDAC in a prospective randomized trial of adjuvant chemotherapy with or without additional chemoradiation therapy (CRT). Patients with postoperative CA19-9 ≤92.5 U/mL and serum bilirubin ≤2 mg/dL were randomized to 2 arms: patients in 1 arm received 6 cycles of gemcitabine, whereas those in the other received 3 cycles of gemcitabine followed by CRT and another 3 cycles of gemcitabine. Serum CA19-9 was measured every 12 weeks. Those who had CA19-9 levels always <3 U/mL were excluded from the exploratory analysis. Results: One hundred forty-seven patients were enrolled in this randomized trial. Twenty-two patients with CA19-9 levels always ≤3 U/mL were excluded from the analysis. For the 125 participants, median overall survival (OS) and recurrence-free survival were 23.1 and 12.1 months, respectively, with no significant differences between the study arms. Postresection CA19-9 levels and, to a lesser extent, CA19-9 change predicted OS (P = .040 and .077, respectively). For the 89 patients who completed the initial 3 cycles of adjuvant gemcitabine, the CA19-9 response was significantly correlated with initial failure over the distant site (P = .023) and OS (P = .0022). Despite a trend of less initial failure over the locoregional area (P = .031), neither postoperative CA19-9 level nor CA19-9 response helped to select patients who might have a survival benefit from additional adjuvant CRT. Conclusions: CA19-9 response to initial adjuvant gemcitabine predicts survival and distant failure of PDAC after resection; however, it cannot select patients suited for additional adjuvant CRT. Monitoring CA19-9 levels during adjuvant therapy for postoperative patients with PDAC may guide therapeutic decisions to prevent distant failure.
MeSH term(s)	Humans ; Pancreatic Neoplasms/pathology ; Prospective Studies ; Adenocarcinoma/pathology ; CA-19-9 Antigen ; Gemcitabine ; Chemotherapy, Adjuvant/methods ; Carbohydrates/therapeutic use ; Pancreatic Neoplasms
Chemical Substances	CA-19-9 Antigen ; Gemcitabine ; Carbohydrates
Language	English
Publishing date	2023-04-11
Publishing country	United States
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	197614-x
ISSN	1879-355X ; 0360-3016
ISSN (online)	1879-355X
ISSN	0360-3016
DOI	10.1016/j.ijrobp.2023.02.061
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Article ; Online: Assessment of fenofibrate-methylation interactions on triglycerides using longitudinal family data

Jih-Chang Yu / Fang-Chi Hsu / Yen-Feng Chiu

BMC Proceedings, Vol 12, Iss S9, Pp 123-

2018 Volume 128

Abstract: Abstract Background Triglyceride (TG) concentrations decrease in response to fenofibrate treatment, and also are associated with DNA methylation. But how interactions between fenofibrate response and DNA methylation affect TGs remains unclear. Methods In ...

Abstract	Abstract Background Triglyceride (TG) concentrations decrease in response to fenofibrate treatment, and also are associated with DNA methylation. But how interactions between fenofibrate response and DNA methylation affect TGs remains unclear. Methods In the present study, we identified and compared differential methylation sites associated with TG concentrations in individuals before and after fenofibrate treatment. We then estimated interactions between fenofibrate treatment and methylation to identify differential methylation effects associated with fenofibrate treatment on TG concentrations using the entire longitudinal family sample. To account for within-family and within-individual corrections, the generalized estimating equations approach was used to estimate main and interaction effects between methylation sites and fenofibrate treatment, adjusting for potential confounders. Analyses were also performed with and without adjusting for high-density lipoprotein (HDL) concentrations. Results Prior to fenofibrate treatment, 23 cytosine-phosphate-guanine (CpG) sites were significantly associated with TG concentrations, while only 13 CpG sites were identified posttreatment, adjusting for HDL. Without adjusting for HDL, pretreatment, 20 CpG sites were significantly associated with TG concentrations, while only 12 CpG sites were identified posttreatment. Among these sites, only one differential site (cg19003390 in the CPT1A gene) overlapped from pre- and posttreatment measurements regardless of HDL adjustment. Furthermore, 11 methylation sites showed substantial interaction effects (p < 1.43 × 10−7with Bonferroni correction) with or without HDL adjustment when using the whole longitudinal data. Conclusions Our analyses suggest that DNA methylation likely modified the effect of fenofibrate on TG concentrations. Differential fenofibrate-associated methylation sites on TGs differed with and without adjusting for HDL concentrations, suggesting that these HDLs and TGs might share some common epigenetic processes.
Keywords	Medicine ; R ; Science ; Q
Subject code	310
Language	English
Publishing date	2018-09-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
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Article ; Online: Region-based association tests for sequencing data on survival traits.

Chien, Li-Chu / Bowden, Donald W / Chiu, Yen-Feng

Genetic epidemiology

2017 Volume 41, Issue 6, Page(s) 511–522

Abstract: Family-based designs enriched with affected subjects and disease associated variants can increase statistical power for identifying functional rare variants. However, few rare variant analysis approaches are available for time-to-event traits in family ... ...

Abstract	Family-based designs enriched with affected subjects and disease associated variants can increase statistical power for identifying functional rare variants. However, few rare variant analysis approaches are available for time-to-event traits in family designs and none of them applicable to the X chromosome. We developed novel pedigree-based burden and kernel association tests for time-to-event outcomes with right censoring for pedigree data, referred to FamRATS (family-based rare variant association tests for survival traits). Cox proportional hazard models were employed to relate a time-to-event trait with rare variants with flexibility to encompass all ranges and collapsing of multiple variants. In addition, the robustness of violating proportional hazard assumptions was investigated for the proposed and four current existing tests, including the conventional population-based Cox proportional model and the burden, kernel, and sum of squares statistic (SSQ) tests for family data. The proposed tests can be applied to large-scale whole-genome sequencing data. They are appropriate for the practical use under a wide range of misspecified Cox models, as well as for population-based, pedigree-based, or hybrid designs. In our extensive simulation study and data example, we showed that the proposed kernel test is the most powerful and robust choice among the proposed burden test and the existing four rare variant survival association tests. When applied to the Diabetes Heart Study, the proposed tests found exome variants of the JAK1 gene on chromosome 1 showed the most significant association with age at onset of type 2 diabetes from the exome-wide analysis.
Language	English
Publishing date	2017-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	605785-8
ISSN	1098-2272 ; 0741-0395
ISSN (online)	1098-2272
ISSN	0741-0395
DOI	10.1002/gepi.22054
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