Statistical methods in collaborative research

该项目的一个重点是为遗传学和流行病学研究开发统计方法。Nodzenski，温伯格和Umbach博士的工作，我们已经扩展了以前发表的方法GADGETS，一个基于遗传算法的方法，以确定遗传上位性效应，使用数据从父母的黑社会，研究环境上位性相互作用，母体遗传效应和胎儿-母体相互作用的影响。与温伯格博士合作的工作重点是评估β几何模型在妊娠时间研究中的性能，该研究于2023年发表在《流行病学》杂志上。在与温伯格和Umbach博士合作的一个项目中，我们正在开发一种使用病例队列研究设计的合并样本分析方法，我们的模拟研究表明，合并多达8个样本仅会导致适度的功效损失。我们还将该方法扩展到使用来自病例队列或病例对照研究的合并样本评估暴露分位数效应。 我积极参与了几项应用研究与多名研究人员在BCBB分支。与Lis博士团队合作，我们正在分析通过睡眠中心收集的睡眠数据。在BMJ Open Respiratory Research上发表的论文中，我们研究了肌营养不良症患者睡眠呼吸暂停和通气不足的特点和关系。我们正在进行分析，以评估睡眠呼吸暂停的性别差异及其随年龄的变化趋势，以及抑郁症与睡眠呼吸暂停之间的关系。 与迪亚兹桑塔纳斯博士团队合作，我们正在使用姐妹研究的数据来验证两种流行的乳腺癌风险预测模型，BOADICEA和Gail模型。在Holle和Park博士领导的一个项目中，我们对5种类胡萝卜素表型进行了GWAS分析，并确定了常见SNP与叶黄素和玉米黄质水平之间的关联。 我还与来自其他分支机构的内部调查人员以及外部调查人员进行了广泛的合作。来自CRU的Rider博士的研究重点是自身免疫性疾病，特别是皮肌炎，一种罕见的炎症性自身免疫性疾病。我与Dr. Riders团队在多个项目上密切合作。我们即将完成一篇描述GWAS对肌炎患者钙质沉着的研究的论文。在另一个项目中，我们评估了扩展的HLA单倍型与罕见肌肉变异和肌炎之间的关联。利用双同胞研究的数据，我们发现全身性风湿性疾病与诊断前几年的生活事件之间存在关联。我也正在与Rider博士合作撰写一份临床试验提案，重点关注Omega 3脂肪酸补充剂对皮肌炎的影响。在与伦敦实验室李慧玲博士的合作中，我们正在准备一份手稿，描述对Adam 19缺陷小鼠肺功能的影响。Fesslers博士的工作组确定了人类受试者中IRGM风险等位基因与细胞因子表达的种族特异性关联。

One focus of this project is on developing statistical methods for genetic and epidemiology studies. Working with Drs. Nodzenski, Weinberg and Umbach, we have extended the previously published method GADGETS, a genetic-algorithm-based method to identify genetic epistatic effects using data from case-parent triads, to studies of environment-epistasis interaction, maternal genetic effects and fetal-maternal interaction effects. The work with Dr. Weinberg focusing on assessing the performance of beta-geometric models in time-to-pregnancy studies was published in Epidemiology in 2023. In a project working with Drs. Weinberg and Umbach we are developing a method for pooled sample analysis using a case-cohort study design and our simulation studies have shown that pooling up to 8 samples only caused modest loss of power. We are also extending the method to assessment of exposure quantile effects using pooled samples from a case-cohort or case-control study. I actively participate in several applied studies collaborating with multiple researchers in BCBB branch. Collaborating with Dr. Lis group we are analyzing the sleep data collected through UNC Sleep Center. In the paper published in BMJ Open Respiratory Research, we studied the characteristics of and relationship between sleep apnea and hypoventilation in patients with muscular dystrophy. We are performing analysis to assess the sex difference in sleep apnea and its trend with age and the relationship between depression and sleep apnea. Working with Dr. Diaz Santanas group we are using data from the Sister Study to validate two popular breast cancer risk prediction models, BOADICEA and Gail models. In a project led by Drs. Holle and Park, we performed a GWAS analysis of 5 carotenoid phenotypes and identified an association between a common SNP and lutein and zeaxanthin levels. I also collaborate extensively with intramural investigators from other branches as well as extramural investigators. The research of Dr Rider from CRU focuses on autoimmune diseases, in particular, dermatomyositis, a rare inflammatory autoimmune disease. I work closely with Dr. Riders group on several projects. We are finishing up writing a paper describing the GWAS study of calcinosis in myositis patients. In another project we evaluated the association between extended HLA haplotypes and rare muscle variants and myositis. Using data from the Twin-Sib study we found an association between systemic rheumatic diseases and life events in the years prior to their diagnosis. I am also working with Dr. Rider to write a clinical trial proposal which focuses on the effects of Omega3 fatty acid supplementation on dermatomyositis. In a collaborative work with Huiling Li from Dr. Londons lab we are preparing a manuscript describing the impact on pulmonary functions in Adam19 deficient mice. Working Dr. Fesslers group we identified race-specific association of IRGM risk alleles with cytokine expression in human subjects.