-
1.
Identification of type 2 diabetes loci in 433,540 East Asian individuals.
Spracklen, CN, Horikoshi, M, Kim, YJ, Lin, K, Bragg, F, Moon, S, Suzuki, K, Tam, CHT, Tabara, Y, Kwak, SH, et al
Nature. 2020;(7811):240-245
-
-
Free full text
-
Abstract
Meta-analyses of genome-wide association studies (GWAS) have identified more than 240 loci that are associated with type 2 diabetes (T2D)1,2; however, most of these loci have been identified in analyses of individuals with European ancestry. Here, to examine T2D risk in East Asian individuals, we carried out a meta-analysis of GWAS data from 77,418 individuals with T2D and 356,122 healthy control individuals. In the main analysis, we identified 301 distinct association signals at 183 loci, and across T2D association models with and without consideration of body mass index and sex, we identified 61 loci that are newly implicated in predisposition to T2D. Common variants associated with T2D in both East Asian and European populations exhibited strongly correlated effect sizes. Previously undescribed associations include signals in or near GDAP1, PTF1A, SIX3, ALDH2, a microRNA cluster, and genes that affect the differentiation of muscle and adipose cells3. At another locus, expression quantitative trait loci at two overlapping T2D signals affect two genes-NKX6-3 and ANK1-in different tissues4-6. Association studies in diverse populations identify additional loci and elucidate disease-associated genes, biology, and pathways.
-
2.
Observational and Genetic Associations of Body Mass Index and Hepatobiliary Diseases in a Relatively Lean Chinese Population.
Pang, Y, Kartsonaki, C, Lv, J, Millwood, IY, Yu, C, Guo, Y, Chen, Y, Bian, Z, Yang, L, Chen, J, et al
JAMA network open. 2020;(10):e2018721
-
-
Free full text
-
Abstract
IMPORTANCE There is some support for the existence of genetic associations between adiposity and certain hepatobiliary diseases in Western populations. However, there is little evidence of such genetic associations in China, where the causes of these diseases may differ from those in Western populations and the mean body mass index (BMI) is much lower. OBJECTIVES To compare the observational associations of BMI with hepatobiliary diseases and liver biomarkers with the genetic associations between BMI and these factors and to assess whether the genetic associations of BMI with liver diseases differed by hepatitis B virus infection status. DESIGN, SETTING, AND PARTICIPANTS This cohort study used data from the prospective China Kadoorie Biobank, including 473 938 adults aged 30 to 79 years without hepatobiliary diseases at baseline from 10 diverse areas in China from June 25, 2004, to July 15, 2008. A random sample of 75 736 participants with genotyping data was included in the Mendelian randomization analysis. Follow-up was completed January 1, 2017 (median [interquartile range] length of follow-up, 10.2 [9.2-11.1] years). Data were analyzed from January to October 2019. EXPOSURES Measured BMI obtained during the baseline survey and genetically instrumented BMI derived using 92 single-nucleotide variations. MAIN OUTCOMES AND MEASURES Incident cases of hepatobiliary diseases, liver enzymes, fatty liver index, and fibrosis score. RESULTS Among 473 938 individuals (276 041 [58.2%] women), the mean (SD) age was 52 (10.9) years and mean (SD) BMI was 23.8 (3.4). Baseline BMI was associated with higher risks of chronic liver disease (adjusted risk ratio per 1-SD increase, 1.14; 95% CI, 1.11 to 1.17) and gallbladder disease (adjusted risk ratio per 1-SD increase, 1.29; 95% CI, 1.27 to 1.31), with heterogeneity by disease subtype (P < .001). Genetically instrumented BMI was associated with higher risks of chronic liver disease (risk ratio per 1-SD increase, 1.55; 95% CI, 1.08 to 2.24) and gallbladder disease (risk ratio per 1-SD increase, 1.40; 95% CI, 1.11 to 1.76), with no heterogeneity between subtypes. A meta-analysis of the genetic associations in China Kadoorie Biobank and those calculated in UK Biobank gave a risk ratio of 1.55 (95% CI, 1.30 to 1.84) for chronic liver disease and 1.42 (95% CI, 1.22 to 1.64) for gallbladder disease. In the China Kadoorie Biobank study, there were positive genetic associations of BMI with liver enzymes, steatosis, and fibrosis scores, consistent with observational associations. The genetic associations of BMI with liver diseases and biomarkers did not differ by hepatitis B virus infection status. CONCLUSIONS AND RELEVANCE In this cohort study of a relatively lean Chinese population, there were positive genetic associations of BMI with hepatobiliary diseases. These results suggest that maintaining a healthy weight through diet and physical activity may help prevent hepatobiliary diseases.
-
3.
HapMap-based study: CYP2A13 may be a potential key metabolic enzyme gene in the carcinogenesis of lung cancer in non-smokers.
Hua, F, Guo, Y, Sun, Q, Yang, L, Gao, F
Thoracic cancer. 2019;(4):601-606
Abstract
BACKGROUND The aim of this study was to evaluate the association between CYP2A13 polymorphisms and lung cancer susceptibility using the HapMap database. METHODS A case-control analysis of 532 subjects with lung cancer and 614 controls with no personal history of the disease was performed. The tag SNPs rs1645690 and rs8192789 for CYP2A13 were selected, and the genetic polymorphisms were confirmed experimentally through real-time PCR, cloning, and sequencing assay. RESULTS SNP frequency in this study was consistent with the HapMap Project database of Han-Chinese and lung cancer risk was associated with CYP2A13 polymorphisms in non-smokers. CYP2A13 shares a 93.5% identity with CYP2A6 in the amino acid sequence and the homologous sequences may interfere with the study of SNPs of CYP2A13. CONCLUSIONS CYP2A13 may be a potential key metabolic enzyme gene in the carcinogenesis of lung cancer in non-smokers. The common polymorphisms of CYP2A13 may be candidate biomarkers for lung cancer susceptibility in Han-Chinese.
-
4.
Association between tea consumption and risk of cancer: a prospective cohort study of 0.5 million Chinese adults.
Li, X, Yu, C, Guo, Y, Bian, Z, Shen, Z, Yang, L, Chen, Y, Wei, Y, Zhang, H, Qiu, Z, et al
European journal of epidemiology. 2019;(8):753-763
-
-
Free full text
-
Abstract
Current experimental and epidemiological studies provide inconsistent evidence toward the association between tea consumption and cancer incidence. We investigated whether tea consumption was associated with the incidence of all cancers and six leading types of cancer (lung cancer, stomach cancer, colorectal cancer, liver cancer, female breast cancer and cervix uteri cancer) among 455,981 participants aged 30-79 years in the prospective cohort China Kadoorie Biobank. Tea consumption was assessed at baseline (2004-2008) with an interviewer-administered questionnaire. Cancer cases were identified by linkage to the national health insurance system. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). In the present population, daily tea consumers were more likely to be current smokers and daily alcohol consumers. 22,652 incident cancers occurred during 10.1 years follow-up (5.04 cases/1000 person-years). When we restricted analyses to non-smokers and non-excessive alcohol consumers to minimize confounding, tea consumption was not associated with all cancers (daily consumers who added tea leaves > 4.0 g/day vs. less-than-weekly consumers: HR, 1.03; 95%CI, 0.93-1.13), lung cancer (HR, 1.08; CI, 0.84-1.40), colorectal cancer (HR, 1.08; CI, 0.81-1.45) and liver cancer (HR, 1.08; CI, 0.75-1.55), yet might be associated with increased risk of stomach cancer (HR, 1.46; CI, 1.07-1.99). In both less-than-daily and daily tea consumers, all cancer risk increased with the amount of tobacco smoked or alcohol consumed. Our findings suggest tea consumption may not provide preventive effect against cancer incidence.
-
5.
Systematic Genetic Analysis of the SMPD1 Gene in Chinese Patients with Parkinson's Disease.
Deng, S, Deng, X, Song, Z, Xiu, X, Guo, Y, Xiao, J, Deng, H
Molecular neurobiology. 2016;(7):5025-9
Abstract
To examine the association between the sphingomyelin phosphodiesterase 1, acid lysosomal (SMPD1) gene, and Parkinson's disease (PD) in Han Chinese from Central South part of Mainland China, we performed systematic genetic analysis in 502 Chinese Han patients with PD and 637 gender-, age-, and ethnicity-matched normal controls from Central South part of the Mainland China. We identified 11 single nucleotide variants and Leu-Ala (Val) repeat variants in the SMPD1 gene in our large cohort. Two novel missense variants, c.638A > C (p.H213P) and c.1673T > C (p.L558P), and a rare known missense variant, c.1805G > A (p.R602H, rs370129081), were identified in three sporadic PD cases. None of these three variants were observed in controls. Additionally, case-control analysis showed association between Leu-Ala (Val) repeat variants in SMPD1 and Chinese Han patients with PD (P = 0.015, χ (2) = 8.451). Our data provide supportive evidence that some genetic variants in SMPD1 increase the risk of PD in the Chinese Han population.
-
6.
Novel CLCN7 mutation identified in a Han Chinese family with autosomal dominant osteopetrosis-2.
Deng, H, He, D, Rong, P, Xu, H, Yuan, L, Li, L, Lu, Q, Guo, Y
Molecular pain. 2016
Abstract
Osteopetrosis is a heritable bone condition featuring increased bone density due to defective osteoclastic bone resorption. Exome sequencing and Sanger sequencing were conducted in Han Chinese family members, some of whom had typical osteopetrosis, and a novel missense variant c.2350A>T (p.R784W) in the chloride channel 7 gene (CLCN7) was identified. This variant cosegregated with the disorder in the family but was not observed in 800 controls. The data indicate that exome sequencing is a powerful and effective molecular diagnostic tool for detecting mutations in osteopetrosis, which is a genetically and clinically heterogeneous disorder. This discovery broadens the CLCN7 gene mutation spectrum and has important implications for clinical therapeutic regimen decisions, prognosis evaluations, and antenatal diagnoses.
-
7.
Accuracy assessment of pharmacogenetic algorithms for warfarin dose prediction in Chinese patients.
Lei, X, Guo, Y, Sun, J, Zhou, H, Liu, Y, Liang, P, Yan, Z
American journal of hematology. 2012;(5):541-4
-
-
Free full text
-
Abstract
A few warfarin pharmacogenetic dosing algorithms have been proposed,based on multiethnic or homogeneous populations, to estimate warfarin therapeutic doses. However, it remains to be proven that which algorithm is accurate in predicting warfarin dose in Chinese people. We selected eight warfarin dose predictive pharmacogenetic algorithms and retrospectively assessed the predictive accuracy of each algorithm in a total of 368 eligible outpatients by comparing the actual stable therapeutic dose to the dose predicted by the algorithm. Our results showed that a high level of performance was demonstrated by three algorithms,Gage et al., Anderson et al., and Wu et al., having a similar performance in coefficient of determination (R2) and percentage of patients predicted dose within 20% of actual dose. The Gage et al. algorithm had the lowest mean absolute error (MAE). These results indicated that the algorithm by Gage et al. provided a more accurate prediction than did the others,which suggests that this pharmacogenetic algorithm might be used in clinical practice to guide rational administration of warfarin.
-
8.
KCNQ1 gene polymorphisms are associated with the therapeutic efficacy of repaglinide in Chinese type 2 diabetic patients.
Dai, XP, Huang, Q, Yin, JY, Guo, Y, Gong, ZC, Lei, MX, Jiang, TJ, Zhou, HH, Liu, ZQ
Clinical and experimental pharmacology & physiology. 2012;(5):462-8
Abstract
The present study evaluated the effects of KCNQ1 rs2237892 and rs2237895 polymorphisms on repaglinide efficacy in Chinese patients with type 2 diabetes mellitus (T2DM). In all, 367 T2DM patients and 214 controls were genotyped. Forty of the T2DM patients were randomly selected to undergo 8 weeks repaglinide treatment. The frequency of the rs2237892 allele was lower in the T2DM patients than in the control group (P < 0.05). The frequency of the rs2237895 C allele was higher in T2DM patients than in healthy control subjects (P < 0.05). Diabetic patients with the rs2237892 risk C allele had lower fasting insulin levels (P < 0.01) and homeostasis model assessment of insulin resistance (HOMA-IR; P < 0.01) values than carriers of the T allele. Diabetic patients with the rs2237895 risk C allele had higher fasting plasma glucose (P < 0.01), postprandial plasma glucose (PPG) levels (P < 0.01) and HOMA-IR values (P < 0.01) than those with the A allele. Following repaglinide treatment, those T2DM patients with the rs2237892 T allele and rs2237895 C allele were more likely to have a positive response to repaglinide in terms of PPG levels (P < 0.05) than T2DM patients with the rs2237892 CC and rs2237895 AA genotypes. In conclusion, KCNQ1 rs2237892 and rs2237895 polymorphisms were found to be associated with the therapeutic efficacy of repaglinide in Chinese T2DM patients.
-
9.
Gene-centric meta-analysis of lipid traits in African, East Asian and Hispanic populations.
Elbers, CC, Guo, Y, Tragante, V, van Iperen, EP, Lanktree, MB, Castillo, BA, Chen, F, Yanek, LR, Wojczynski, MK, Li, YR, et al
PloS one. 2012;(12):e50198
Abstract
Meta-analyses of European populations has successfully identified genetic variants in over 100 loci associated with lipid levels, but our knowledge in other ethnicities remains limited. To address this, we performed dense genotyping of ∼2,000 candidate genes in 7,657 African Americans, 1,315 Hispanics and 841 East Asians, using the IBC array, a custom ∼50,000 SNP genotyping array. Meta-analyses confirmed 16 lipid loci previously established in European populations at genome-wide significance level, and found multiple independent association signals within these lipid loci. Initial discovery and in silico follow-up in 7,000 additional African American samples, confirmed two novel loci: rs5030359 within ICAM1 is associated with total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) (p = 8.8×10(-7) and p = 1.5×10(-6) respectively) and a nonsense mutation rs3211938 within CD36 is associated with high-density lipoprotein cholesterol (HDL-C) levels (p = 13.5×10(-12)). The rs3211938-G allele, which is nearly absent in European and Asian populations, has been previously found to be associated with CD36 deficiency and shows a signature of selection in Africans and African Americans. Finally, we have evaluated the effect of SNPs established in European populations on lipid levels in multi-ethnic populations and show that most known lipid association signals span across ethnicities. However, differences between populations, especially differences in allele frequency, can be leveraged to identify novel signals, as shown by the discovery of ICAM1 and CD36 in the current report.