Genetic influences on alcohol flushing in East Asian populations.

Background: Although it is known that variation in the aldehyde dehydrogenase 2 (ALDH2) gene family influences the East Asian alcohol flushing response, knowledge about other genetic variants that affect flushing symptoms is limited.

Methods: We performed a genome-wide association study meta-analysis and heritability analysis of alcohol flushing in 15,105 males of East Asian ancestry (Koreans and Chinese) to identify genetic associations with alcohol flushing. We also evaluated whether self-reported flushing can be used as an instrumental variable for alcohol intake.

Proteome-wide Mendelian randomization in global biobank meta-analysis reveals multi-ancestry drug targets for common diseases.

Proteome-wide Mendelian randomization (MR) shows value in prioritizing drug targets in Europeans but with limited evidence in other ancestries. Here, we present a multi-ancestry proteome-wide MR analysis based on cross-population data from the Global Biobank Meta-analysis Initiative (GBMI). We estimated the putative causal effects of 1,545 proteins on eight diseases in African (32,658) and European (1,219,993) ancestries and identified 45 and 7 protein-disease pairs with MR and genetic colocalization evidence in the two ancestries, respectively.

Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects.

Estimates from genome-wide association studies (GWAS) of unrelated individuals capture effects of inherited variation (direct effects), demography (population stratification, assortative mating) and relatives (indirect genetic effects). Family-based GWAS designs can control for demographic and indirect genetic effects, but large-scale family datasets have been lacking. We combined data from 178,086 siblings from 19 cohorts to generate population (between-family) and within-sibship (within-family) GWAS estimates for 25 phenotypes.

Childhood body size directly increases type 1 diabetes risk based on a lifecourse Mendelian randomization approach.

The rising prevalence of childhood obesity has been postulated as an explanation for the increasing rate of individuals diagnosed with type 1 diabetes (T1D). In this study, we use Mendelian randomization (MR) to provide evidence that childhood body size has an effect on T1D risk (OR = 2.05 per change in body size category, 95% CI = 1.

Applying Mendelian randomization to appraise causality in relationships between nutrition and cancer.

Dietary factors are assumed to play an important role in cancer risk, apparent in consensus recommendations for cancer prevention that promote nutritional changes. However, the evidence in this field has been generated predominantly through observational studies, which may result in biased effect estimates because of confounding, exposure misclassification, and reverse causality. With major geographical differences and rapid changes in cancer incidence over time, it is crucial to establish which of the observational associations reflect causality and to identify novel risk factors as these may be modified to prevent the onset of cancer and reduce its progression.

Avoiding dynastic, assortative mating, and population stratification biases in Mendelian randomization through within-family analyses.

Estimates from Mendelian randomization studies of unrelated individuals can be biased due to uncontrolled confounding from familial effects. Here we describe methods for within-family Mendelian randomization analyses and use simulation studies to show that family-based analyses can reduce such biases. We illustrate empirically how familial effects can affect estimates using data from 61,008 siblings from the Nord-Trøndelag Health Study and UK Biobank and replicated our findings using 222,368 siblings from 23andMe.

The Dysfunctional Autonomic Function and "Dysfunctional" Fatigue in Drug Naïve Parkinson's Disease.

Background: Fatigue is a common and disabling non-motor symptom in Parkinson's disease (PD). Autonomic dysfunction is suggested as the possible pathophysiology of fatigue, but it has not been investigated in drug-naïve PD patients.

Objective: In the present study, the relationship between fatigue and autonomic dysfunction in drug-naïve PD patients was investigated.

Exploiting horizontal pleiotropy to search for causal pathways within a Mendelian randomization framework.

In Mendelian randomization (MR) analysis, variants that exert horizontal pleiotropy are typically treated as a nuisance. However, they could be valuable in identifying alternative pathways to the traits under investigation. Here, we develop MR-TRYX, a framework that exploits horizontal pleiotropy to discover putative risk factors for disease.

Association of circulating 25-hydroxyvitamin D levels with hypertension and blood pressure values in Korean adults: A Mendelian randomization study on a subset of the Korea National Health and Nutrition Survey 2011-2012 population.

Background/objectives: Lower circulating 25-hydroxyvitamin D [25(OH)D] levels are associated with a higher risk of hypertension (HTN); however, it remains unclear whether the relationship is causal. We aimed to evaluate the causal effects of circulating 25(OH)D levels on the prevalence of HTN in the Korean population using the Mendelian randomization (MR) approach.

Subjects/methods: Epidemiological data, serum 25(OH)D data, and genomic DNA biospecimens were obtained from 2,591 participants, a subset of the study population in the Korea National Health and Nutrition Survey 2011-2012.

Differential value of brain magnetic resonance imaging in multiple system atrophy cerebellar phenotype and spinocerebellar ataxias.

Clinically differentiating multiple system atrophy cerebellar (MSA-C) phenotype and spinocerebellar ataxias (SCAs) is challenging especially in the early stage. We assessed diagnostic value of brain magnetic resonance imaging (MRI) in differentiating MSA-C and SCAs based at different disease stages (<3, 3-7, and >7 years of disease duration). Overall, 186 patients with probable MSA-C and 117 with genetically confirmed SCAs were included.

Exploring the utility of alcohol flushing as an instrumental variable for alcohol intake in Koreans.

Previous studies have indicated an association of higher alcohol intake with cardiovascular disease and related traits, but causation has not been definitively established. In this study, the causal effect of alcohol intake on hypertension in 2,011 men and women from the Ansan-Ansung cohort was estimated using an instrumental variable (IV) approach, with both a phenotypic and genotypic instrument for alcohol intake: alcohol flushing and the rs671 genotype (in the alcohol dehydrogenase 2 [ALDH2] gene), respectively. Both alcohol flushing and the rs671 genotype were associated with alcohol intake (difference in alcohol intake with alcohol flushers vs.

Alcohol Consumption, Aldehyde Dehydrogenase 2 Gene Polymorphisms, and Cardiovascular Health in Korea.

Alcohol consumption is a serious health issue in Korea in terms of the amount consumed and the behavior related to its consumption. Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme in alcohol metabolism that degrades acetaldehyde to nontoxic acetic acid. The enzyme is coded by the ALDH2 gene, which is commonly polymorphic in East Asian populations.

Burdens of Cardiometabolic Diseases Attributable to Dietary and Metabolic Risks in Korean Adults 2012-2013.

Purpose: In line with epidemiological and sociocultural changes in Korea over the past decades, reliable estimation of diseases as a result of dietary and metabolic risks is required. In this study, we aimed to evaluate the contributions of dietary and metabolic factors to cardiometabolic diseases (CMDs) in Korean adults (25-64 years old) during 2012-2013.

Materials And Methods: Distribution of risk factors and cause-specific mortality by gender and age per year was obtained from the Korea National Health and Nutrition Examination Survey and Statistics Korea, respectively.

Estimating change in cardiovascular disease and diabetes burdens due to dietary and metabolic factors in Korea 1998-2011: a comparative risk assessment analysis.

Objectives: Over the past 10 years, the burden of chronic diseases in Korea has increased. However, there are currently no quantitative estimates of how changes in diet and metabolic factors have contributed to these shifting burdens. This study aims to evaluate the contributions of dietary and metabolic risk factors to death from cardiometabolic diseases (CMDs) such as cardiovascular conditions, strokes and diabetes in Korea, and to estimate how these contributions have changed over the past 10 years (1998-2011).

Association between Genetic Variations Affecting Mean Telomere Length and the Prevalence of Hypertension and Coronary Heart Disease in Koreans.

In this study, we investigated whether the single nucleotide polymorphisms (SNPs) associated with telomere length (TL) were associated with the incidence of hypertension (HTN)/coronary heart disease (CHD) and cardiovascular risk factors in the Korean population. Data from 5,705 (ages 39-70) participants in the Korean Genome Epidemiology Study (rural Ansung and urban Ansan cohorts) were studied. Twelve SNPs known to be associated with telomere biology were tested for an association with HTN/CHD.

Association of dietary intakes of total and subtypes of fat substituted for carbohydrate with metabolic syndrome in Koreans.

Amount of fat consumption has gradually increased among Koreans, which is relatively lower than western countries. In the current study, we examined the association between dietary fat and metabolic syndrome (MetS) prevalence among Korean adults. 3,212 participants who are aged 30-74 years from the Korea National Health and Nutritional Examination Survey (KNHANES) VI (2013) were included for cross-sectional analyses.

Serum gamma-glutamyl transferase and risk of type 2 diabetes in the general Korean population: a Mendelian randomization study.

Elevated gamma-glutamyl transferase (GGT) levels are associated with higher risk of type 2 diabetes in observational studies, but the underlying causal relationship is still unclear. Here, we tested a hypothesis that GGT levels have a causal effect on type 2 diabetes risk using Mendelian randomization. Data were collected from 7640 participants in a South Korean population.

Beneficial effects of voglibose administration on body weight and lipid metabolism via gastrointestinal bile acid modification.

This study was designed with the goal of examining the effects of voglibose administration on body weight and lipid metabolism and underlying mechanism high fat diet-induced obese mice. Male C57BL/6 mice were randomly assigned to one of four groups: a control diet (CTL), high-fat diet (HF), high-fat diet supplemented with voglibose (VO), and high fat diet pair-fed group (PF). After 12 weeks, the following characteristics were investigated: serum lipid and glucose levels, serum polar metabolite profiles, and expression levels of genes involved in lipid and bile acid metabolism.

Alcohol intake and cardiovascular risk factors: A Mendelian randomisation study.

Mendelian randomisation studies from Asia suggest detrimental influences of alcohol on cardiovascular risk factors, but such associations are observed mainly in men. The absence of associations of genetic variants (e.g.

Plasma phospholipid arachidonic acid and lignoceric acid are associated with the risk of cardioembolic stroke.

Cardioembolic (CE) stroke is the most severe subtype of ischemic stroke with high recurrence and mortality. However, there is still little information on the association of plasma fatty acid (FA) with CE stroke. The objective of this study was to test the hypothesis whether the composition of plasma phospholipid FA is associated with the risk of CE stroke.

Dietary Very Long Chain Saturated Fatty Acids and Metabolic Factors: Findings from the Korea National Health and Nutrition Examination Survey 2013.

The present study was aim to evaluate the association between very long chain saturated fatty acids (VLSFAs) and metabolic syndrome (MetS) in Korean population. The study population were recruited from the Korea National Health and Nutrition Examination Survey VI (2013). Using the cross-sectional study design, socio-demographic factors, medical history, and clinical measurements were investigated according to quartiles of VLSFAs intake.

Association between age at menarche and diabetes in Korean post-menopausal women: results from the Korea National Health and Nutrition Examination Survey (2007-2009).

Early menarche is known to be associated with diabetes, however this association remains controversial. Our study aimed to investigate the possible association between age at menarche and diabetes prevalence in post-menopausal Korean women. This study included 3,254 post-menopausal Korean women aged 50-85 years from the Korea National Health and Nutrition Examination Survey IV (KNHANES 2007-2009).