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The major causes and risk factors of total and cause-specific mortality during 5.4-year follow-up: the Shanghai Changfeng Study.
Wu, L, Lin, H, Hu, Y, Zhu, C, Ma, H, Gao, J, Wu, J, Shen, H, Jiang, W, Zhao, N, et al
European journal of epidemiology. 2019;(10):939-949
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Abstract
To investigate the major causes and predictive factors of death in a middle-aged and elderly Chinese population. A total of 6591 residents aged ≥ 45 years from Shanghai Changfeng community were followed up for an average of 5.4 years. The causes of death were coded according to the 10th Revision of International Classification of Diseases. The mortality rate was calculated by person-years of follow up and age-standardized according to the 2010 Chinese census data. Multivariable-adjusted Cox proportional hazards model was performed to investigate the predictors of all-cause and cause-specific mortality. During the total follow-up of 35,739 person-years, 370 deaths were documented (157 from malignant neoplasms, 70 from heart diseases, 68 from cerebrovascular diseases, 75 from other causes). The age-standardized all-cause mortality rate was 798.2 per 100,000 person-years (927.9 among men and 716.7 among women). Results from multivariable analyses showed that aging, diabetes, and osteoporosis at baseline were independent predictors of all-cause mortality, with hazard ratios (HR) of 1.11 (95% CI 1.10-1.13), 1.91 (1.51-2.42), and 1.71 (1.24-2.35), respectively. The population attributable risk percent of diabetes and osteoporosis was 19.7% and 11.7%, respectively. Cigarette smoking was associated with a higher risk of all-cause mortality in men (HR and 95%CI 1.44, 1.01-2.06). In women, diabetes and osteoporosis were related to a higher risk of cardiovascular mortality (3.27, 1.82-5.88 and 1.89, 1.04-3.46, respectively). While in men, osteoporosis was related to a higher risk of malignant neoplasms mortality (2.39, 1.07-5.33). Malignant neoplasms, heart diseases, and cerebrovascular diseases are the leading causes of death. Aging, smoking, underweight, diabetes, and osteoporosis are independent predictors of premature death among middle-aged and elderly Chinese community population. Moreover, there may have been some differences in the causes and predictors of premature death between men and women.
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Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci.
He, M, Xu, M, Zhang, B, Liang, J, Chen, P, Lee, JY, Johnson, TA, Li, H, Yang, X, Dai, J, et al
Human molecular genetics. 2015;(6):1791-800
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Abstract
Human height is associated with risk of multiple diseases and is profoundly determined by an individual's genetic makeup and shows a high degree of ethnic heterogeneity. Large-scale genome-wide association (GWA) analyses of adult height in Europeans have identified nearly 180 genetic loci. A recent study showed high replicability of results from Europeans-based GWA studies in Asians; however, population-specific loci may exist due to distinct linkage disequilibrium patterns. We carried out a GWA meta-analysis in 93 926 individuals from East Asia. We identified 98 loci, including 17 novel and 81 previously reported loci, associated with height at P < 5 × 10(-8), together explaining 8.89% of phenotypic variance. Among the newly identified variants, 10 are commonly distributed (minor allele frequency, MAF > 5%) in Europeans, with comparable frequencies with in Asians, and 7 single-nucleotide polymorphisms are with low frequency (MAF < 5%) in Europeans. In addition, our data suggest that novel biological pathway such as the protein tyrosine phosphatase family is involved in regulation of height. The findings from this study considerably expand our knowledge of the genetic architecture of human height in Asians.
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Exploring causal associations of alcohol with cardiovascular and metabolic risk factors in a Chinese population using Mendelian randomization analysis.
Taylor, AE, Lu, F, Carslake, D, Hu, Z, Qian, Y, Liu, S, Chen, J, Shen, H, Smith, GD
Scientific reports. 2015;:14005
Abstract
Observational studies suggest that moderate alcohol consumption may be protective for cardiovascular disease, but results may be biased by confounding and reverse causality. Mendelian randomization, which uses genetic variants as proxies for exposures, can minimise these biases and therefore strengthen causal inference. Using a genetic variant in the ALDH2 gene associated with alcohol consumption, rs671, we performed a Mendelian randomization analysis in 1,712 diabetes cases and 2,076 controls from Nantong, China. Analyses were performed using linear and logistic regression, stratified by sex and diabetes status. The A allele of rs671 was strongly associated with reduced odds of being an alcohol drinker in all groups, but prevalence of alcohol consumption amongst females was very low. The A allele was associated with reduced systolic and diastolic blood pressure and decreased total and HDL cholesterol in males. The A allele was also associated with decreased triglyceride levels, but only robustly in diabetic males. There was no strong evidence for associations between rs671 and any outcomes in females. Our results suggest that associations of alcohol consumption with blood pressure and HDL-cholesterol are causal. Alcohol also appeared to have adverse effects on triglyceride levels, although this may be restricted to diabetics.
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Genome-wide association study in Chinese identifies novel loci for blood pressure and hypertension.
Lu, X, Wang, L, Lin, X, Huang, J, Charles Gu, C, He, M, Shen, H, He, J, Zhu, J, Li, H, et al
Human molecular genetics. 2015;(3):865-74
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Abstract
Hypertension is a common disorder and the leading risk factor for cardiovascular disease and premature deaths worldwide. Genome-wide association studies (GWASs) in the European population have identified multiple chromosomal regions associated with blood pressure, and the identified loci altogether explain only a small fraction of the variance for blood pressure. The differences in environmental exposures and genetic background between Chinese and European populations might suggest potential different pathways of blood pressure regulation. To identify novel genetic variants affecting blood pressure variation, we conducted a meta-analysis of GWASs of blood pressure and hypertension in 11 816 subjects followed by replication studies including 69 146 additional individuals. We identified genome-wide significant (P < 5.0 × 10(-8)) associations with blood pressure, which included variants at three new loci (CACNA1D, CYP21A2, and MED13L) and a newly discovered variant near SLC4A7. We also replicated 14 previously reported loci, 8 (CASZ1, MOV10, FGF5, CYP17A1, SOX6, ATP2B1, ALDH2, and JAG1) at genome-wide significance, and 6 (FIGN, ULK4, GUCY1A3, HFE, TBX3-TBX5, and TBX3) at a suggestive level of P = 1.81 × 10(-3) to 5.16 × 10(-8). These findings provide new mechanistic insights into the regulation of blood pressure and potential targets for treatments.
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Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations.
Wu, C, Wang, Z, Song, X, Feng, XS, Abnet, CC, He, J, Hu, N, Zuo, XB, Tan, W, Zhan, Q, et al
Nature genetics. 2014;(9):1001-1006
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Abstract
We conducted a joint (pooled) analysis of three genome-wide association studies (GWAS) of esophageal squamous cell carcinoma (ESCC) in individuals of Chinese ancestry (5,337 ESCC cases and 5,787 controls) with 9,654 ESCC cases and 10,058 controls for follow-up. In a logistic regression model adjusted for age, sex, study and two eigenvectors, two new loci achieved genome-wide significance, marked by rs7447927 at 5q31.2 (per-allele odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.82-0.88; P = 7.72 × 10(-20)) and rs1642764 at 17p13.1 (per-allele OR = 0.88, 95% CI = 0.85-0.91; P = 3.10 × 10(-13)). rs7447927 is a synonymous SNP in TMEM173, and rs1642764 is an intronic SNP in ATP1B2, near TP53. Furthermore, a locus in the HLA class II region at 6p21.32 (rs35597309) achieved genome-wide significance in the two populations at highest risk for ESSC (OR = 1.33, 95% CI = 1.22-1.46; P = 1.99 × 10(-10)). Our joint analysis identifies new ESCC susceptibility loci overall as well as a new locus unique to the population in the Taihang Mountain region at high risk of ESCC.
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Genetic variant in fat mass and obesity-associated gene associated with type 2 diabetes risk in Han Chinese.
Qian, Y, Liu, S, Lu, F, Li, H, Dong, M, Lin, Y, Du, J, Lin, Y, Gong, J, Jin, G, et al
BMC genetics. 2013;:86
Abstract
BACKGROUND Genome-wide association study (GWAS) has identified that rs8050136 C/A polymorphism in fat mass and obesity-associated gene (FTO) was associated with the risk of type 2 diabetes (T2D) in Europeans. But this association was abolished after adjustment for body mass index (BMI), suggesting that the effect of rs8050136 on T2D risk might be mediated by BMI in Europeans. However, the findings in subsequent studies were inconsistent among Asian populations. To determine whether rs8050136 polymorphism in FTO is independently associated with the risk of T2D in Chinese, we conducted a case-control study with 2,925 T2D patients and 3,281 controls in Han Chinese. RESULTS Logistic regression revealed that the A allele of rs8050136 was significantly associated with an increased risk of T2D, independent of BMI (odds ratio (OR) = 1.17, 95% confidence interval (95% CI) = 1.03-1.32, p = 0.016). Meta-analysis containing 10 reported studies and our data with a total of 15,819 cases and 18,314 controls further confirmed the association between rs8050136 polymorphism and T2D risk in East Asians (OR = 1.13, 95% CI = 1.07-1.19). CONCLUSIONS Our findings indicate that the genetic variant in FTO may contribute to T2D risk in Han Chinese and rs8050136 polymorphism may be a genetic marker for T2D susceptibility.
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Mutational screening of 10 genes in Chinese patients with microphthalmia and/or coloboma.
Zhang, X, Li, S, Xiao, X, Jia, X, Wang, P, Shen, H, Guo, X, Zhang, Q
Molecular vision. 2009;:2911-8
Abstract
PURPOSE To screen ten genes for mutations in 32 Chinese patients with microphthalmia and/or coloboma. METHODS Genomic DNA was prepared from 32 unrelated patients with microphthalmia (nine probands) and uveal coloboma (23 probands). Cycle sequencing was used to detect sequence variations in ten genes, including BMP4, VSX2, CRYBA4, GDF6, OTX2, RAX, SIX3, SIX6, SOX2, and LRP6. Variations were further evaluated in 96 unrelated controls by using restriction fragment length polymorphism (RFLP) or heteroduplex-single strand conformation polymorphism (HA-SSCP) analysis. RESULTS In the ten genes, a novel c.751C>T (p.H251Y) in BMP4 was detected in a patient with bilateral microphthalmia and unilateral cataract. The c.751C>T variation is also present in his healthy brother (and possibly one of the normal parents). In addition, a novel c.608G>A (p.R203Q) in SIX6 was identified in an internal control for optimizing experimental conditions. The internal control was from a girl with typical aniridia and an identified c.718C>T (p.R240X) mutation in PAX6, suggesting the c.608G>A variation in SIX6 was unlikely to play a role in her ocular phenotype. The c.751C>T in BMP4 and the c.608G>A in SIX6 were not present in the 96 normal controls. In addition, 16 nucleotide substitutions, including eight known SNPs and eight new synonymous changes, were detected. CONCLUSIONS Although the genetic etiology for microphthalmia and/or coloboma is still elusive, rare variations in the related genes, such as c.608 G>A in SIX6 and c.751C>T in BMP4, may not be causative. These results further emphasize the importance of careful clinical and genetic analysis in making mutation-disease associations.