Investigating the molecular mechanisms and consequences of assortative mating in major psychiatric disorders: completing a missing piece of the psychiatric genetics puzzle

研究主要精神疾病中选型交配的分子机制和后果：完成精神遗传学难题中缺失的一块

• 批准号: 9545065
• 负责人: James Joseph Crowley
• 金额: $ 14.42万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-15 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9545065
• 关键词: Affect; Attention deficit hyperactivity disorder; Biological Testing; Bipolar Disorder; Child; Complex; Consent; Data; Development; Diagnosis; Disease; Early Intervention; Environment; Environmental Impact; Environmental Risk Factor; Equilibrium; Fertility; Funding; Generalized Anxiety Disorder; Generations; Genes; Genetic; Genetic Risk; Genetic screening method; Genotype; Goals; Height; Heritability; Homo; Incidence; Individual; Institutes; Investments; Link; Literature; Maintenance; Major Depressive Disorder; Medical; Mental disorders; Molecular; Obsessive-Compulsive Disorder; Outcome; Parents; Partner in relationship; Pattern; Personality; Persons; Phenotype; Play; Population; Population Control; Population Sizes; Prevalence; Preventive Intervention; Process; Psychiatric Diagnosis; Psychiatry; Reporting; Research; Resources; Rights; Risk; Risk Assessment; Role; SNP genotyping; Sampling; Scandinavia; Schizophrenia; Shapes; Signal Transduction; Social Phobia; Spouses; Substance abuse problem; Sweden; Techniques; Testing; Time; Weight; Work; case control; data access; disorder control; disorder risk; genetic variant; genome wide association study; health data; high risk population; offspring; proband; psychogenetics; risk variant; simulation; trait; transmission process

PROJECT SUMMARY Recent research has indicated that individuals diagnosed with a major psychiatric disorder are more likely than healthy individuals to select a mate with their own or an alternative psychiatric condition. What role this nonrandom mating may play in the transmission of psychiatric illness, however, remains unclear. Where parents are homotypic for a disorder (e.g., both parents have a diagnosis of schizophrenia), offspring will receive genetic variants from each parent that are related to that disorder – placing them at particularly high genetic risk for that condition's development. However, this type of compounded genetic risk may also occur in heterotypic pairings (e.g., one parent having schizophrenia, the other bipolar disorder), as many psychiatric conditions share genetic risks. With prior research suggesting that such heterotypic pairings are pervasive in psychiatric populations, understanding the degree to which risks are sustained in these offspring is an important question. The primary goal of this proposal is, therefore, to leverage the unique scale of data available in the Swedish Medical Registers to determine the change in risk for major psychiatric diagnoses, among the offspring of parents who are homotypic or heterotypic for major psychiatric diagnoses, relative to the risk in offspring of single affected or healthy parents. Parents with any of eight major psychiatric diagnoses - attention deficit hyperactivity disorder, bipolar disorder, generalized anxiety disorder, major depressive disorder, obsessive- compulsive disorder, schizophrenia, social phobia, and substance abuse – will be considered in this work, with the incidence of these conditions in their offspring compared to the incidence in matched population controls. In addition to describing these risks, this project also proposes to examine the degree of overlap in risk variants for a particular condition – schizophrenia – among the parents of offspring diagnosed with this condition. If found, this type of molecular correlation would signal a clear mechanism by which a disorder may arise in offspring of homo- or heterotypic pairs, while its absence could suggest a stronger role for environment in shaping these added risks.

项目摘要 最近的研究表明，被诊断患有严重精神疾病的人比那些患有精神疾病的人更有可能患上精神疾病。 健康的人选择一个伴侣与自己或替代的精神疾病。什么角色 然而，非随机交配可能在精神疾病的传播中起作用，这一点仍不清楚。哪里 父母对于疾病是同型的（例如，父母双方都有精神分裂症的诊断），后代将 从每个父母那里获得与该疾病相关的遗传变异-将它们置于特别高的水平 遗传风险的发展。然而，这种类型的复合遗传风险也可能发生在 异型配对（例如，父母一方患有精神分裂症，另一方患有双相情感障碍）， 条件共享遗传风险。先前的研究表明，这种异型配对是普遍存在的， 精神病人群，了解这些后代的风险程度是一个 重要的问题。 因此，该提案的主要目标是利用瑞典语中独特的数据规模， 医学登记册，以确定主要精神病诊断的风险变化，在后代中， 对于主要精神病诊断，父母是同型或异型的，相对于后代的风险， 单身或健康的父母。父母有任何八个主要的精神病诊断-注意力缺陷 多动障碍，双相情感障碍，广泛性焦虑障碍，重度抑郁障碍，强迫症- 强迫症，精神分裂症，社交恐惧症和药物滥用-将在这项工作中考虑， 这些疾病在其后代中的发生率与匹配的对照人群中的发生率相比。 除了描述这些风险外，本项目还建议检查风险变量的重叠程度 一种特殊的疾病-精神分裂症-在被诊断患有这种疾病的后代的父母中。如果 发现，这种类型的分子相关性将发出一个明确的机制，通过该机制， 同源或异型对的后代，而它的缺失可能表明环境在 形成这些额外的风险。