Comparison of dimension reduction-based logistic regression models for case-control genome-wide association study:principal components analysis vs.partial least squares

With recent advances in biotechnology, genome-wide association study （GWAS） has been widely used to identify genetic variants that underlie human complex diseases and traits. In case-control GWAS, typical statistical strategy is traditional logistical regression （LR） based on single-locus analysis. However, such a single-locus analysis leads to the well-known multiplicity problem, with a risk of inflating type I error and reducing power. Dimension reduction-based techniques, such as principal component-based logistic regression （PC-LR）, partial least squares-based logistic regression （PLS-LR）, have recently gained much attention in the analysis of high dimensional genomic data. However, the perfor- mance of these methods is still not clear, especially in GWAS. We conducted simulations and real data application to compare the type I error and power of PC-LR, PLS-LR and LR applicable to GWAS within a defined single nucleotide polymorphism （SNP） set region. We found that PC-LR and PLS can reasonably control type I error under null hypothesis. On contrast, LR, which is corrected by Bonferroni method, was more conserved in all simulation settings. In particular, we found that PC-LR and PLS-LR had comparable power and they both outperformed LR, especially when the causal SNP was in high linkage disequilibrium with genotyped ones and with a small effective size in simulation. Based on SNP set analysis, we applied all three methods to analyze non-small cell lung cancer GWAS data.

Ideal cardiovascular health and mortality:pooled results of three prospective cohorts in Chinese adults

Background: Evidence on the relations of the American Heart Association’s ideal cardiovascular health (ICH) with mortality in Asians is sparse, and the interaction between behavioral and medical metrics remained unclear. We aimed to fill the gaps. Methods: A total of 198,164 participants without cancer and cardiovascular disease (CVD) were included from the China Kadoorie Biobank study (2004-2018), Dongfeng-Tongji cohort (2008-2018), and Kailuan study (2006-2019). Four behaviors (i.e., smoking, physical activity, diet, body mass index) and three medical factors (i.e., blood pressure, blood glucose, and blood lipid) were classified into poor, intermediate, and ideal levels (0, 1, and 2 points), which constituted 8-point behavioral, 6-point medical, and 14-point ICH scores. Results of Cox regression from three cohorts were pooled using random-effects models of meta-analysis. Results: During about 2 million person-years, 20,176 deaths were recorded. After controlling for demographic characteristics and alcohol drinking, hazard ratios (95% confidence intervals) comparing ICH scores of 10-14 vs. 0-6 were 0.52 (0.41-0.67), 0.44 (0.37-0.53), 0.54 (0.45-0.66), and 0.86 (0.64-1.14) for all-cause, CVD, respiratory, and cancer mortality. A higher behavioral or medical score was independently associated with lower all-cause and CVD mortality among the total population and populations with different levels of behavioral or medical health equally, and no interaction was observed. Conclusions: ICH was associated with lower all-cause, CVD, and respiratory mortality among Chinese adults. Both behavioral and medical health should be improved to prevent premature deaths.

Neutralization against SARS-CoV-2 Delta/Omicron variants and B cell response after inactivated vaccination among COVID-19 convalescents

Emerging SARS-CoV-2 variants have made COVID-19 convalescents susceptible to re-infection and have raised concern about the efficacy of inactivated vaccination in neutralization against emerging variants and antigen-specific B cell response.To this end,a study on a long-term cohort of 208 participants who have recovered from COVID-19 was conducted,and the participants were followed up at 3.3(Visit 1),9.2(Visit 2),and 18.5(Visit 3)months after SARS-CoV-2 infection.They were classified into three groups(no-vaccination(n=54),one-dose(n=62),and two-dose(n=92)groups)on the basis of the administration of inactivated vaccination.The neutralizing antibody(NAb)titers against the wild-type virus continued to decrease in the no-vaccination group,but they rose significantly in the one-dose and two-dose groups,with the highest NAb titers being observed in the two-dose group at Visit 3.The NAb titers against the Delta variant for the no-vaccination,one-dose,and two-dose groups decreased by 3.3,1.9,and 2.3 folds relative to the wild-type virus,respectively,and those against the Omicron variant decreased by 7.0,4.0,and 3.8 folds,respectively.Similarly,the responses of SARS-CoV-2 RBD-specific B cells and memory B cells were boosted by the second vaccine dose.Results showed that the convalescents benefited from the administration of the inactivated vaccine(one or two doses),which enhanced neutralization against highly mutated SARS-CoV-2 variants and memory B cell responses.Two doses of inactivated vaccine among COVID-19 convalescents are therefore recommended for the prevention of the COVID-19 pandemic,and vaccination guidelines and policies need to be updated.

Effectiveness of inactivated COVID-19 vaccine against the severity of Omicron variant

The COVID-19 pandemic has led to unprecedented levels of morbidity,mortality,and economic disruption worldwide.Several non-pharmaceutical interventions have been implemented worldwide to curb the spread of SARS-CoV-2,including social distancing,home isolation,and centralized quarantine[1].Nevertheless,these interventions cannot be sustained over the longterm.Current hopes of controlling the pandemic rely heavily on vaccination,which remains the best tool available for preventing infection and symptomatic illness.

大气二氧化氮与每日总死亡率、心血管和呼吸系统疾病死亡率的短期关联:398个城市的多中心分析

目的:采用统一的分析方案,评估全球多个国家/地区的二氧化氮(NO_(2))与总死亡率、心血管和呼吸系统疾病死亡率之间的短期关联。研究设计:采用两阶段的时间序列分析方法、过度离散的广义线性模型和多水平meta分析。研究地点:22个低到高收入国家/地区的398个城市。主要结局指标:1973—2018年逐日总死亡人数(6280万人)、心血管疾病死亡人数(1970万人)和呼吸系统疾病死亡人数(550万人)。结果:平均而言,NO_(2)浓度在滞后1天(前1天)每增加10μg/m^(3),会导致总死亡率、心血管和呼吸系统疾病死亡率分别增加0.46%(95%可信区间0.36%~0.57%)、0.37%(0.22%~0.51%)、0.47%(0.21%~0.72%)。在对共污染物(PM_(10)、PM_(2.5)、臭氧、二氧化硫和一氧化碳)进行调整后,这些关联仍然很稳定。所有3种死因的暴露-反应曲线几乎是线性的,没有明显的阈值。在398个城市中,可归因于高过假定零水平的NO_(2)浓度造成的死亡比例为1.23%(95%可信区间0.96%~1.51%)。结论:这项多中心研究提供了关于NO_(2)短期暴露与总死亡率、心血管和呼吸系统死亡风险之间的独立和线性关联的关键证据,说明通过加强NO_(2)的控制和监管限制标准,可获得人群水平的健康收益。

Alternations in the gut microbiota and metabolome with newly diagnosed unstable angina

Gut microbiota plays an important role in coronary heart disease, but its compositional and functional changes in unstable angina(UA) remain unexplored. We performed metagenomic sequencing of 133 newly diagnosed UA patients and 133 sex-and age-matched controls, and profiled the fecal and plasma metabolomes in 30 case-control pairs. The alpha diversity of gut microbiota was increased in UA patients:the adjusted odds ratios(ORs) per standard deviation increase in Shannon and Simpson indices were 1.30(95% confidence interval, 1.01-1.70) and 1.36(1.05-1.81), respectively. Two common species(depleted Klebsiella pneumoniae and enriched Streptococcus parasanguinis;P ≤ 0.002) and three rare species(depleted Weissella confusa, enriched Granulicatella adiacens and Erysipelotrichaceae bacterium 6_1_45;P ≤ 0.005) were associated with UA. The UA-associated gut microbiota was depleted in the pathway of Lphenylalanine degradation(P = 0.001), primarily contributed by Klebsiella pneumoniae. Consistently, we found increased circulating phenylalanine in UA patients(OR = 2.76 [1.17-8.16]). Moreover, Streptococcus parasanguinis was negatively correlated with fecal citrulline(Spearman's r_(s)=-0.470, P = 0.009), a metabolite depleted in UA patients(OR = 0.26 [0.08-0.63]). These findings are informative to help understand the metabolic connection between gut microbiota and UA.

Dynamics of the SARS-CoV-2 antibody response up to 10 months after infection

COVID-19 caused by SARS-CoV-2 infection has caused substantial morbidity and mortality worldwide and paralyzed the international economy.Understanding the magnitude and duration of the antibody response to SARS-CoV-2 is important to achieve a balance between curbing the pandemic and minimizing adverse effects on society.1 Although the antibody response to SARS-CoV-2 within 9 months has been extensively studied,2,3,4,5,6 little is known about the magnitude and kinetics of antibody responses for over 9 months.Moreover,with limited observations over 9 months(n<100),2,7,8 several studies have produced inconsistent conclusions about antibody dynamics,suggesting different rates of antiviral antibody positivity at the last follow-up.2,7,8 These studies have been limited by a lack of measurement of neutralizing antibodies(NAbs),7 of inclusion of mild or asymptomatic cases,2,8 and of further exploration of potential predisposing factors for antibody dynamics.2,7 Considering the individual heterogeneity(such as disease severity)8 and time-dependent nature1 of the immune response,in-depth characterization of SARS-CoV-2 antibody kinetics across disease severity groups over a long period is urgently needed.Therefore,we repeatedly tested IgM,IgG,viral spike protein receptor-binding dom(anti-RBD)IgG,and NAb titers in COVID-19 patients during a follow-up period of up to 10 months and explored potential predisposing factors of antibody titers during follow-up.

Persistence of humoral and cellular immune response after SARS-CoV-2 infection: opportunities and challenges

The emerging COVID-19 pandemic caused by SARSCoV-2 infection has created a global crisis.Under the circumference of no effective treatment or vaccine,the Chinese government has implemented multifaceted measures of social distancing,home isolation,and centralized quarantine,which achieved a remarkable result of controlling the COVID-19 outbreak[1].However,the personal,psychological,economic,and societal consequences of the shutdown and physical distancing make it difficult to sustain these public health interventions for a long time[2].To find a new balance between curbing the pandemic and minimizing the indirect effects on society,a better understanding of adaptive immunity in response to SARS-CoV-2 infection is required.

The role of natriuretic peptide precursor A gene polymorphism in the development of coronary heart disease in Chinese Han population

Natriuretic peptide precursor A(NPPA)is synthesized,stored,and released by atrial myocytes.Previous studies have shown that NPPA plays a significant role in the regulation of coronary circulation and in atherosclerosis.Rs5065 NPPA gene polymorphism leads to the translation of NPPA with two additional arginines and has been suggested to be associated with salt-sensitive hypertension.The purpose of the present study was to investigate the relationship between the rs5065 NPPA gene polymorphism and the risk of coronary heart disease(CHD)in Chinese Han population.We genotyped the single nucleotide polymorphism(SNP)rs5065 NPPA in the human NPPA gene in 1861 sex-and age-matched subjects,comprising of 904 CHD cases and 957 controls of Chinese Han population.Genotyping of SNP was performed with Taqman SNP allelic discrimination assays by means of an ABI 7900HT.Our study showed that the frequencies of rs5065 NPPA C allele in the case and the control groups were 0.012 and 0.005,respectively.There was significant difference in C allele frequency distribution between the two groups(OR=2.607,95%CI:1.197–5.678,P=0.012).In the case group,there was significant difference between smokers and nonsmokers with subjects carrying C allele(P=0.037),and no significant difference in gender,age,fasting total cholesterol(TC),triglycerides(TG),fasting plasma glucose(FPG),body mass index(BMI),and blood pressure(BP)between the cases and the controls(P>0.05).Our results suggest that the C allele of rs5065 NPPA gene polymorphism may be associated with the risk of CHD.

Independent and Combined Associations of Sleep Duration, Bedtime, and Polygenic Risk Score with the Risk of Hearing Loss among Middle-Aged and Old Chinese: The Dongfeng–Tongji Cohort Study

Evidence available on the independent and combined associations of sleep duration,bedtime,and genetic predisposition with hearing loss was lacking.The present study included 15,827 participants from the Dongfeng–Tongji cohort study.Genetic risk was characterized by polygenic risk score(PRS)based on 37 genetic loci related to hearing loss.We conducted multivariate logistic regression models to assess the odds ratio(OR)for hearing loss with sleep duration and bedtime,as well as the joint association and interaction with PRS.Results showed that hearing loss was independently associated with sleeping≥9 h/night compared to the recommended 7 to<8 h/night,and with bedtime≤9:00 p.m.and>9:00 p.m.to 10:00 p.m.compared to those with bedtime>10:00 p.m.to 11:00 p.m.,with estimated ORs of 1.25,1.27,and 1.16,respectively.