Elucidating the barriers and facilitators to widespread implementation of preconception genetic carrier screening

对未来父母进行筛查，以确定他们的后代是否存在潜在破坏性遗传风险 基因携带者筛查的情况已导致新生儿数量明显减少 受严重隐性疾病的影响。尽管像美国大学这样的专业团体 妇产科医生和美国医学遗传学学院倡导基因携带者 在怀孕前进行筛查(未孕)，获得未孕基因携带者筛查 仍然是低和不公平的。这是因为在不同的国家实施了载体筛查 人口是复杂的，需要1)了解各级筛查的障碍和促进者 医疗保健交付，2)识别患者对测试交付的偏好，以及3)澄清潜在的个人 携带者筛查对健康的影响。这一奖项将被用来解决我们在 了解先入为主的遗传携带者筛查。首先，我将采访有经验的关键线人 在医疗保健提供的所有级别了解他们对实施以下目标的障碍和促进者的看法 先入为主的携带者筛查计划。其次，我将系统地了解病人的喜好。 应使用离散选择实验进行遗传携带者筛查。不连续的选择 实验将由一项基于网络的调查组成，其中不同的属性如何携带先入为主的概念 提供的筛查方法多种多样，潜在患者必须选择他们首选的筛查方法。这 将对两个不同的育龄妇女队列进行调查，以鼓励 回应。最后，我将使用全表型关联性研究方法来调查携带者是否 常染色体隐性遗传病是其他成人疾病的高危人群。我将重点介绍CFTR、HBB和GBA， 与常染色体隐性遗传病、囊性纤维化、镰状细胞性贫血和高谢尔有关 疾病，分别。这项研究将产生关键的试点数据，用于设计可测试的实现 能够广泛使用先入为主的携带者筛查的策略。这些战略及其对 病人护理随后将通过未来的拨款申请在随机临床试验中进行测试。

Screening of prospective parents to determine if their offspring are at risk for potentially devastating heritable conditions with genetic carrier screening has resulted in measurable decreases in the number of newborns affected by severe recessive disorders. Although professional societies such as the American College of Obstetricians and Gynecologists and the American College of Medical Genetics advocate for genetic carrier screening to be done prior to pregnancy (preconception), access to preconception genetic carrier screening remains low and inequitable. This is because implementation of carrier screening in a diverse national population is complicated and requires 1) understanding the barriers and facilitators of screening at all levels of healthcare delivery, 2) recognizing patient preferences for test delivery, and 3) clarifying potential personal health implications of carrier screening. This award will be used to address these three gaps in our understanding of preconception genetic carrier screening. First, I will interview key informants with experience at all levels of healthcare delivery about their perceptions of the barriers and facilitators to implementing preconception carrier screening programs. Second, I will systematically elicit patient preferences about how genetic carrier screening should be delivered using a discrete choice experiment. The discrete choice experiment will consist of a web-based survey in which different attributes of how preconception carrier screening is offered are varied and prospective patients must choose their preferred screening method. This survey will be administered to two separate cohorts of women of reproductive age to encourage a diversity of responses. Finally, I will use phenome-wide association study methods to investigate whether carriers of autosomal recessive disease are at high risk of other adult diseases. I will focus on CFTR, HBB, and GBA, which are implicated in the autosomal recessive disorders cystic fibrosis, sickle cell anemia, and Gaucher disease, respectively. This study will generate key pilot data that will be used to design testable implementation strategies to enable widespread use of preconception carrier screening. These strategies and their impact on patient care will subsequently be tested in a randomized clinical trial through a future grant application.