Disentangling the Epidemiologic and Genetic Heterogeneity of Postpartum Depression to Predict Risk and Prognosis

项目总结 产后抑郁症(PPD)是一种常见的分娩并发症，其发病率和死亡率对 母亲和孩子，但病因学仍然知之甚少。PPD是MDD的一个更易遗传的亚型，但意义重大 PPD表型中存在异质性，这可能反映了病因学上的差异。这项研究旨在 通过利用来自全球独一无二的 资源、挪威母婴队列研究(MOBA)和产后抑郁症的美国分支机构： 针对病因和治疗联盟的行动。这项研究的目的是1)应用现代统计学习 方法在一个主训练集(N=63,528)和两个独立测试集(N=31,716和N=4,978)中 确定PPD亚型，2)确定PPD亚型的遗传贡献者以及与其他性状的遗传重叠 3)研究PPD亚型对长期心理健康预后的预测程度。 这项研究将支持我的主要职业目标，成为一名独立资助的调查员 进行综合性流行病学和基因组研究以了解复杂性所需的专业知识 产后抑郁的病因学。我的长期研究目标是开发全面的风险预测模型， 最终转化为有效的预防性干预措施和针对产后抑郁的新型个体化治疗。我 我有流行病学和围产期健康方面的专业知识，但我需要额外的指导培训来进行大规模- 大规模、综合的基因-环境分析，以了解产后抑郁的生物学基础。具体目标 实现我的职业目标是：1)培养数据科学技能，有效分析大型、复杂的数据集；2) 建立对基因组学和统计遗传学的深入理解，以及3)理解复杂性 产后抑郁和其他相关精神疾病的表型。核心导师团队由Samantha博士组成 首席导师、国际公认的围产期心理健康研究专家Meltzer-Brody和Dr。 帕特里克·沙利文，共同领导导师，精神病学遗传学家，建立了抑郁症的合作网络 在斯堪的纳维亚半岛进行研究。李云博士，联合导师，在开发统计和 基因组和高维数据的计算方法。泰德·赖希伯恩-克杰纳鲁德博士，共同导师，以及 合作者Helga Ask博士和Alexandra Havdahl博士在精神病学评估方面拥有丰富的经验 在莫巴队列中的结果。凯瑟琳·刘易斯博士，合作者，是遗传学发展的领先专家 风险评分方法。他们的共同指导将把我置于一个理想的位置，使我成为一名 独立调查员。 这项工作将为进一步研究基因和环境对发育的独特贡献提供信息 PPD的多因素预测模型，代表着向个性化医疗迈出的重要一步 围产期心理健康。我在获奖期间获得的重要技能将为未来的研究奠定基础 评估产后抑郁的预防和个体化治疗的干预措施。

PROJECT SUMMARY Postpartum depression (PPD), a common complication of childbirth, has significant morbidity and mortality for mother and child, yet etiology is still poorly understood. PPD is a more heritable subtype of MDD, yet significant heterogeneity exists within the PPD phenotype, which may reflect differences in etiology. This study aims to disentangle the heterogeneity of PPD to understand etiology by leveraging existing data from two unique global resources, the Norwegian Mother and Child Cohort Study (MoBa) and the US arm of the Postpartum Depression: Action Towards Causes and Treatment Consortium. The study aims to 1) apply modern statistical learning methods in a master training set (N=63,528) and two independent testing sets (N=31,716 and N=4,978) to identify PPD subtypes, 2) identify genetic contributors to PPD subtypes and genetic overlap with other traits, and 3) examine the extent to which PPD subtypes predict longer-term mental health prognosis. This research will support my primary career goal to become an independently funded investigator with the expertise necessary to conduct integrated epidemiologic and genomic research to understand the complex etiology of PPD. My long-term research objective is to develop comprehensive risk prediction models that can ultimately be translated into effective preventive interventions and novel individualized treatments for PPD. I have expertise is in epidemiology and perinatal health, but I need additional mentored training to conduct large- scale, integrated gene-environment analyses to understand the biological basis of PPD. The specific objectives to meet my career goal are to 1) develop skills in data science to effectively analyze large, complex datasets, 2) establish an in-depth understanding of genomics and statistical genetics, and 3) understand the complex phenotypes of PPD and other related psychiatric conditions. The core mentorship team consists of Dr. Samantha Meltzer-Brody, lead mentor, an internationally recognized expert in perinatal mental health research, and Dr. Patrick Sullivan, co-lead mentor, a psychiatric geneticist who has built a collaborative network of depression research in Scandinavia. Dr. Yun Li, co-mentor, has extensive experience in developing statistical and computational methods for genomic and high-dimensional data. Dr. Ted Reichborn-Kjennerud, co-mentor, and Drs. Helga Ask and Alexandra Havdahl, collaborators, have extensive experience with assessment of psychiatric outcomes in the MoBa cohort. Dr. Cathryn Lewis, collaborator, is a leading expert in the development of genetic risk score methodology. Their combined mentorship will place me in an ideal position to succeed as an independent investigator. This work will inform further investigation of unique contributions of genes and environment to develop multifactorial predictive models for PPD, representing an important step towards personalized medicine in perinatal mental health. The vital skills I attain during this grant award will provide a foundation for future research evaluating interventions for prevention and personalized therapeutic treatments of PPD.