Publications by authors named "Kei Hang Katie Chan"

6 Publications

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The 2020 FASEB virtual Catalyst Conference on Integrative Approach for Complex Diseases Prevention and Management and Beyond, December 16, 2020.

FASEB J 2021 07;35(7):e21500

Herbert Wertheim School of Public Health and Human Longevity, University of California, San Diego, CA, USA.

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http://dx.doi.org/10.1096/fj.202100317DOI Listing
July 2021

The trans-ancestral genomic architecture of glycemic traits.

Nat Genet 2021 06 31;53(6):840-860. Epub 2021 May 31.

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
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http://dx.doi.org/10.1038/s41588-021-00852-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610958PMC
June 2021

The Lung Cancer Associated MicroRNAs and Single Nucleotides Polymorphisms: a Mendelian Randomization Analysis.

Annu Int Conf IEEE Eng Med Biol Soc 2020 07;2020:2346-2352

Lung cancer is a major public health burden and among the highest incidence and mortality rates of the cancers. MicroRNAs (miRNAs) play an important role in the development of lung cancer. The aim of this study was to investigate whether there was a potential causal relation between miRNAs and non-small-cell lung cancer (NSCLC). 1,026 patients with NSCLC from The Cancer Genome Atlas (TCGA) were analyzed. NSCLC associated SNPs' allele scores were established, and candidate miRNAs were filtered from differential expression analysis. Mendelian randomization (MR) analysis was conducted for 5 candidate miRNA (hsa-miR-135b, hsa-miR-142, hsa-miR-182, hsa-miR-183 and hsa-miR-3607) and 76 candidate SNPs in lung adenocarcinoma (LUAD) group. According to the core assumptions of MR, there was no clear evidence of a causal relation between the 5 candidate miRNAs and LUAD. The reads per million miRNAs mapped (RPM) level of candidate miRNAs changed less than 3% per allele score. To our knowledge, this is the first study using the TCGA data set to investigate the causal relation between miRNAs and lung cancer using the MR approach, and also one of the first MR studies to use miRNA expression as an exposure factor, with the SNPs as instrumental variables.
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http://dx.doi.org/10.1109/EMBC44109.2020.9176344DOI Listing
July 2020

Understanding the relation between socioeconomic position and inflammation in post-menopausal women: education, income and occupational prestige.

Eur J Public Health 2017 12;27(6):1074-1079

Department of Epidemiology and Biostatistics, Drexel University, Philadelphia, PA, USA.

Background: The role of occupational prestige, a direct measure of the perceived status of job and job holder, in inflammation is unknown. To contribute to understanding the pathways by which socioeconomic position (SEP) is associated with inflammation, we aimed to estimate the direct effects of education, income and occupational prestige on C-reactive protein (CRP) and to describe the relationship between these markers and CRP.

Methods: The study was based on 2026 post-menopausal women enrolled in the Women's Health Initiative-Observational Study. Occupational prestige was determined by linking a text description of longest held occupation with a social status item from the Occupational Information Network. Path analysis was employed to estimate direct and mediated effects.

Results: The study suggests that higher levels of education, income, and occupational prestige are associated with 8% (95% CI as percentage change -12, -4), 5% [95% CI (-8, -2) and 4% (95% CI - 7, -1)] lower levels of CRP, respectively. The inverse association between education and CRP was explained by the effect of education on income and occupational prestige. The effect of occupational prestige on CRP was independent of mediators in the model.

Conclusions: The findings indicate that education may work to influence CRP primarily through increasing income and occupational prestige and provides evidence that occupational prestige captures a unique aspect of SEP.
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http://dx.doi.org/10.1093/eurpub/ckx070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5881793PMC
December 2017

Relationship between dietary carbohydrates intake and circulating sex hormone-binding globulin levels in postmenopausal women.

J Diabetes 2018 Jun 14;10(6):467-477. Epub 2017 May 14.

Department of Epidemiology, Brown University School of Public Health, Providence, Rhode Island, USA.

Background: Low circulating levels of sex hormone-binding globulin (SHBG) have been shown to be a direct and strong risk factor for type 2 diabetes, cardiovascular diseases, and hormone-dependent cancers, although the relationship between various aspects of dietary carbohydrates and SHBG levels remains unexplored in population studies.

Methods: Among postmenopausal women with available SHBG measurements at baseline (n = 11 159) in the Women's Health Initiative, a comprehensive assessment was conducted of total dietary carbohydrates, glycemic load (GL), glycemic index (GI), fiber, sugar, and various carbohydrate-abundant foods in relation to circulating SHBG levels using multiple linear regressions adjusting for potential covariates. Linear trend was tested across quartiles of dietary variables. Benjamini and Hochberg's procedure was used to calculate the false discovery rate for multiple comparisons.

Results: Higher dietary GL and GI (both based on total and available carbohydrates) and a higher intake of sugar and sugar-sweetened beverages were associated with lower circulating SHBG concentrations (all P  < 0.05; Q -values = 0.04,0.01, 0.07, 0.10, 0.01, and <0.0001, respectively). In contrast, women with a greater intake of dietary fiber tended to have elevated SHBG levels (P  = 0.01, Q -value = 0.04). There was no significant association between total carbohydrates or other carbohydrate-abundant foods and SHBG concentrations.

Conclusions: The findings suggest that low GL or GI diets with low sugar and high fiber content may be associated with higher serum SHBG concentrations among postmenopausal women. Future studies investigating whether lower GL or GI diets increase SHBG concentrations are warranted.
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http://dx.doi.org/10.1111/1753-0407.12550DOI Listing
June 2018

Rare Loss-of-Function Variants in Predispose to Human Obesity.

Diabetes 2017 04 27;66(4):935-947. Epub 2017 Jan 27.

Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, MD.

Some Shanghai Clinical Center f a role of Niemann-Pick type C1 () for obesity traits. However, whether the loss-of-function mutations in cause adiposity in humans remains unknown. We recruited 25 probands with rare autosomal-recessive Niemann-Pick type C (NP-C) disease and their parents in assessment of the effect of heterozygous mutations on adiposity. We found that male carriers had a significantly higher BMI than matched control subjects or the whole population-based control subjects. Consistently, male mice had increased fat storage while eating a high-fat diet. We further conducted an in-depth assessment of rare variants in the gene in young, severely obese subjects and lean control subjects and identified 17 rare nonsynonymous/frameshift variants in (minor allele frequency <1%) that were significantly associated with an increased risk of obesity (3.40% vs. 0.73%, respectively, in obese patients and control subjects, = 0.0008, odds ratio = 4.8, 95% CI 1.7-13.2), indicating that rare variants were enriched in young, morbidly obese Chinese subjects. Importantly, participants carrying rare variants with severely damaged cholesterol-transporting ability had more fat accumulation than those with mild/no damage rare variants. In summary, rare loss-of-function mutations were identified as being associated with human adiposity with a high penetrance, providing potential therapeutic interventions for obesity in addition to the role of in the familial NP-C disease.
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http://dx.doi.org/10.2337/db16-0877DOI Listing
April 2017