A Variational Bayes Discrete Mixture Test for Rare Variant Association

Recently, many statistical methods have been proposed to test for associations between rare genetic variants and complex traits. Most of these methods test for association by aggregating genetic variations within a predefined region, such as a gene. Although there is evidence that “aggregate” tests are more powerful than the single marker test, these tests generally ignore neutral variants and therefore are unable to identify specific variants driving the association with phenotype. We propose a novel aggregate rare‐variant test that explicitly models a fraction of variants as neutral, tests associations at the gene‐level, and infers the rare‐variants driving the association. Simulations show that in the practical scenario where there are many variants within a given region of the genome with only a fraction causal our approach has greater power compared to other popular tests such as the Sequence Kernel Association Test (SKAT), the Weighted Sum Statistic (WSS), and the collapsing method of Morris and Zeggini (MZ). Our algorithm leverages a fast variational Bayes approximate inference methodology to scale to exome‐wide analyses, a significant computational advantage over exact inference model selection methodologies. To demonstrate the efficacy of our methodology we test for associations between von Willebrand Factor (VWF) levels and VWF missense rare‐variants imputed from the National Heart, Lung, and Blood Institute's Exome Sequencing project into 2,487 African Americans within the VWF gene. Our method suggests that a relatively small fraction (～10%) of the imputed rare missense variants within VWF are strongly associated with lower VWF levels in African Americans.     

Pre-conceptional Folic Acid Supplement Use According to Maternal Country of Birth

BackgroundSupplementation with folic acid tablets in the pre-conceptional period reduces the risk of neural tube defects (NTD). In Canada, the risk of NTD may differ across certain ethnic groups. It is not known whether pre-conceptional folic acid supplement use varies according to a woman’s country of birth or her duration of residency in Canada.MethodsWe included 6349 Canadian women who gave birth between January 2005 and December 2006, and who had participated in the nationally representative Maternity Experiences Survey. Reported use of a supplement containing folic acid in the three months prior to conception was evaluated in association with maternal place of birth, categorized by nine regions of the world. Odds ratios (OR) were adjusted for maternal age, gravidity, income, education level, gestational age at first prenatal care visit, and number of years living in Canada.ResultsRelative to a rate of 61% among Canadian-born mothers, the adjusted OR for pre-conceptional use of supplements containing folic acid was significantly lower among those who emigrated from the Caribbean and Latin America (OR 0.46; 95% confidence interval [CI] 0.31–0.70), Northern Africa and the Middle East (OR 0.33; 95% CI 0.20–0.57), and China and the South Pacific (OR 0.55; 95% CI 0.40–0.78).ConclusionCertain groups of women who are immigrants to Canada take pre-conceptional folic acid supplements at rates much lower than Canadian-born women. Interventions aimed at increasing folic acid use might focus on these women, perhaps around their time of arrival in Canada.     

Persistent problems of access to appropriate,affordable TB services in rural China: experiences of different socio-economic groups

Background  

Large-scale Tuberculosis (TB) control programmes in China have been hailed a success. Concerns remain, however, about whether the programme is reaching all sections of the population, particularly poorer groups within rural communities, and whether there are hidden costs. This study takes a household perspective to investigate receipt of appropriate care and affordability of services for different socio-economic groups with TB symptoms in rural China.     

我国突发公共卫生事件后勤保障、公众教育和人员培训能力现状评价

目的:评价当前我国突发公共卫生事件后勤保障、公众教育和人员培训能力的现状.方法:采用分层抽样随机抽取4个省(市)作为调查样本,采用卫生部统计信息中心编制的<省/地级市突发公共卫生事件应对能力问卷>进行调查.结果:共发放问卷66份,问卷回收率为90.91%.80%的地市(州)有专门机构负责应急物资储备、管理和调配工作,65%的地市(州)制定了应急物资储备清单和标准,35%的地市(州)制定了应急物资储备点的标准,25%的地市(州)制定了突发公共卫生事件应急储备物资定期检测、维护和更新管理办法,45%的地市(州)制定了日常工作财政预算,27%的地市(州)建立了应急资金的储备标准,28%的地市(州)制定了应急储备资金紧急调用程序,4省(市)后勤保障子问卷平均标准得分为43.33,总体均数的95%置信区间为(35.65～51.01).25%的地市(州)在近2年中开展培训需求调查,53%的地市(州)制定了应急人员培训规划,20%的地市(州)制定了应急人员培训效果评价办法,80%的地市(州)指定了专门机构负责公众教育工作,23%的地市(州)制定了公众教育管理办法.4省(市)公众教育和人员培训子问卷标准得分均数为47.43,总体均数的95%置信区间为(40.69～54.17).结论:当前我国突发公共卫生事件后勤保障、公众教育和人员培训能力方面尚存在不少问题,各级政府应迅速采取措施加强这几方面的能力.     

Rationale and design of the National Program of Cancer Registries' breast, colon, and prostate cancer patterns of care study

Background: Investigators from the Centers for Disease Control and Prevention (CDC), National Program of Cancer Registries (NPCR), are collaborating with public health professionals from seven states and the District of Columbia to conduct the Patterns of Care study to assess the quality of cancer data and to determine whether stage-specific treatments are being carried out. Methods: To assess the quality and completeness of cancer care data in the United States, trained staff from the Patterns of Care study are abstracting medical records to obtain detailed clinical data on treatment, tumor characteristics, stage at diagnosis, and demographics of representative samples of patients diagnosed with breast, colon, and prostate cancer. Altogether staff from each of the eight participating cancer registries will abstract 500 cases of breast, prostate, and colon/rectum/anus cancer for the CONCORD study and an additional 150 cases of localized breast cancer, 100 cases of stage III colon cancer, and 100 cases of localized prostate cancer for the Patterns of Care study. Chi-square tests will be used to compare routine registry data with re-abstracted data. The investigators will use logistic regression techniques to describe the characteristics of patients with localized breast and prostate cancer and stage III colon cancer. Age, race, sex, type of insurance, and comorbidity will be examined as predictors of the use of those treatments that are consistent with consensus guidelines. The investigators plan to use data from the CONCORD study to determine whether treatment factors are the reason for the reported differences between relative survival rates in the United States and Europe. Conclusions Results from the methodology used in the Patterns of Care study will provide, for the first time, detailed information about the quality and completeness of stage and treatment data that are routinely collected by states participating in the NPCR. It will add significantly to our understanding of factors that determine receipt of treatment in compliance with established guidelines. As part of the CONCORD study, it will also examine differences in survival among cancer patients with breast, prostate, and colon/rectum/anus cancers in the United States and Europe.     

Characteristics of men receiving vasectomies in the United States, 1998-1999

CONTEXT: Even though vasectomy is a popular method of contraception in the United States, there is limited information on the characteristics of men choosing vasectomy and why they decide to undergo the procedure.
METHODS: A nationwide, practice-based survey of 719 men receiving vasectomies was conducted between July 1998 and June 1999.
RESULTS: Low-income, minority and less educated men were underrepresented among vasectomy recipients. The majority of men were married or cohabiting (91%), non-Hispanic and white (87%), and educated beyond high school (81%). Only 7% of men had annual household incomes of less than $25,000, and fewer than 1% paid for the procedure using public funding; 81% of respondents paid through private insurance or a health maintenance organization. Half of men reported choosing vasectomy over a reversible method because it is the most secure means of preventing pregnancy, and 62% chose vasectomy over tubal ligation because the procedure is simpler and safer. Doctors and nurses were the most important sources of information about vasectomy (cited by 31% of respondents), followed by wives or partners (25%) and friends (23%).
CONCLUSIONS: Despite the diversity of the U.S. population, vasectomy recipients are a homogeneous group. By identifying users of vasectomy and underserved groups, our findings should assist service providers and program managers in planning strategies to reduce the large difference in levels of vasectomy use among men of different races, ethnicities and income groups.