Aldehyde dehydrogenase 2—a potential genetic risk factor for lung function among southern Chinese: evidence from the Guangzhou Biobank Cohort Study

Yeung, Shiu Lun Au; Jiang, Chaoqiang; Cheng, Kar Keung; Adab, Peymané; Lam, Kin Bong Hubert; Liu, Bin; Zhang, Weisen; Lam, Tai Hing; Leung, Gabriel M.; Schooling, CM

doi:10.1016/j.annepidem.2014.05.015

Cited by 4 publications

(6 citation statements)

References 32 publications

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“…93,94 Another common study design is cohort sampling, where all biobank patients with available data meeting the inclusion criteria are included in the analysis. 38,95 Self-controlled designs in which each patient serves as his/her own control are emerging as an appealing design paradigm for some scientific problems. 96,97 Two variations of self-controlled designs are the self-controlled case series design and the case-crossover design.…”

Section: Defining the Study Samplementioning

confidence: 99%

The emerging landscape of health research based on biobanks linked to electronic health records: Existing resources, statistical challenges, and potential opportunities

Beesley

Salvatore

Fritsche

et al. 2019

Statistics in Medicine

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Biobanks linked to electronic health records provide rich resources for health‐related research. With improvements in administrative and informatics infrastructure, the availability and utility of data from biobanks have dramatically increased. In this paper, we first aim to characterize the current landscape of available biobanks and to describe specific biobanks, including their place of origin, size, and data types. The development and accessibility of large‐scale biorepositories provide the opportunity to accelerate agnostic searches, expedite discoveries, and conduct hypothesis‐generating studies of disease‐treatment, disease‐exposure, and disease‐gene associations. Rather than designing and implementing a single study focused on a few targeted hypotheses, researchers can potentially use biobanks' existing resources to answer an expanded selection of exploratory questions as quickly as they can analyze them. However, there are many obvious and subtle challenges with the design and analysis of biobank‐based studies. Our second aim is to discuss statistical issues related to biobank research such as study design, sampling strategy, phenotype identification, and missing data. We focus our discussion on biobanks that are linked to electronic health records. Some of the analytic issues are illustrated using data from the Michigan Genomics Initiative and UK Biobank, two biobanks with two different recruitment mechanisms. We summarize the current body of literature for addressing these challenges and discuss some standing open problems. This work complements and extends recent reviews about biobank‐based research and serves as a resource catalog with analytical and practical guidance for statisticians, epidemiologists, and other medical researchers pursuing research using biobanks.

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Section: Defining the Study Samplementioning

confidence: 99%

The emerging landscape of health research based on biobanks linked to electronic health records: Existing resources, statistical challenges, and potential opportunities

Beesley

Salvatore

Fritsche

et al. 2019

Statistics in Medicine

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“…People with slow metabolization of acetaldehyde due to inactive ALDH2 alleles may feel ill after drinking alcohol, and so in settings where alcohol use is discretionary tend to drink less. The ALDH2 polymorphism rs671 has previously been used by us and others in MR studies to assess the effects of moderate alcohol use on cardiovascular disease risk factors and cognitive function [ 18 – 20 ].…”

Section: Introductionmentioning

confidence: 99%

Alcohol Use and Gamma-Glutamyltransferase Using a Mendelian Randomization Design in the Guangzhou Biobank Cohort Study

Jiang

Cheng

et al. 2015

PLoS ONE

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BackgroundObservational studies and small intervention studies suggest alcohol raises gamma-glutamyltransferase (GGT). We used Mendelian randomization to assess the causal effect of alcohol use on GGT in older Chinese people.MethodsAn instrumental variable (IV) analysis in 2,321 men and 2,757 women aged 50+ years from phase 3 of the Guangzhou Biobank Cohort Study with ALDH2 (rs671) genotyped, alcohol use and GGT available was used to assess the causal effect of alcohol use on GGT. Rs671 was used as an IV and F-statistics was used to test for weak instrument hypothesis. An F-statistic of ≥10 indicates the IV is not weak.ResultsIn men, the F-statistic for rs671 on alcohol use was 70. Using IV analysis alcohol use increased GGT by 10.60 U/L per alcohol unit (10 gram ethanol) per day (95% confidence interval (CI) 6.58 to 14.62). The estimate was lower in observational multivariate regression: 3.48 U/L GGT per alcohol unit per day (95% CI 2.84 to 4.11) adjusted for age, education, physical activity and smoking. In women, rs671 was not associated with alcohol or GGT and the F-statistic was 7 precluding IV analysis.ConclusionIn Mendelian randomization, we found confirmative evidence that alcohol use increases GGT among Southern Chinese men. Moreover, we found that the ALDH2 variant rs671 was not associated with GGT among Southern Chinese women who generally consume very low levels of alcohol. Taken together our findings strongly suggest that alcohol increases GGT, although we cannot rule out the possibility that other unknown factors may cause a different relation between alcohol and GGT in other populations.

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“…The decrease of ALDH2 activity is attributed to the impaired binding affinity to coenzyme, NAD + (ref. 36 ) and triggers the facial flushing caused by alcohol intake 37 38 and local inflammatory diseases 39 40 41 . The heterozygous rs671 shows 6% of the normal activity, and homozygous variant shows almost negative activity 18 .…”

Section: Discussionmentioning

confidence: 99%

Three missense variants of metabolic syndrome-related genes are associated with alpha-1 antitrypsin levels

et al. 2015

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Alpha-1 antitrypsin (AAT) encoded by SERPINA1 is an acute-phase inflammation marker, and AAT deficiency (AATD) is known as one of the common genetic disorders in European populations. However, no genetic determinants to AAT levels apart from the SERPINA gene clusters have been identified to date. Here we perform a genome-wide association study of serum AAT levels followed by a two-staged replication study recruiting a total of 9,359 Japanese community-dwelling population. Three missense variants of metabolic syndrome-related genes, namely, rs671 in ALDH2, rs1169288 in HNF1A and rs1260326 in GCKR, significantly associate with AAT levels (P≤1.5 × 10−12). Previous reports have shown the functional relevance of ALDH2 and HNF1A to AAT. We observe a significant interaction of rs671 and alcohol consumption on AAT levels. We confirm the association between AAT and rs2896268 in SERPINA1, which is independent of known causative variants of AATD. These findings would support various AAT functions including metabolic processes.

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Aldehyde dehydrogenase 2—a potential genetic risk factor for lung function among southern Chinese: evidence from the Guangzhou Biobank Cohort Study

Abstract: Previous findings in Chinese may be confounded by ALDH2. High frequency of inactive ALDH2 alleles in East Asia may exacerbate the effect of environmental acetaldehyde exposure on lung function and potentially on chronic obstructive pulmonary disease.

Cited by 4 publications

References 32 publications

The emerging landscape of health research based on biobanks linked to electronic health records: Existing resources, statistical challenges, and potential opportunities

The emerging landscape of health research based on biobanks linked to electronic health records: Existing resources, statistical challenges, and potential opportunities

Alcohol Use and Gamma-Glutamyltransferase Using a Mendelian Randomization Design in the Guangzhou Biobank Cohort Study

Three missense variants of metabolic syndrome-related genes are associated with alpha-1 antitrypsin levels

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