Seasonality of Mood: A Genome-Wide Association Study in the Old Order Amish

情绪的季节性：旧秩序阿米什人的全基因组关联研究

• 批准号: 8035847
• 负责人: TEODOR T POSTOLACHE
• 金额: $ 12.18万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-20 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8035847
• 关键词: Accounting; Affect; Age; Air; American; Amish; Anhedonia; Animals; Appearance; Behavior; Behavioral; Biological; Biological Response Modifiers; Breeding; Calendar; Candidate Disease Gene; Carbohydrates; Cardiovascular system; Chemicals; Cholesterol; Custom; DNA; Disease remission; Eating; Effectiveness; Electricity; Environment; Environmental Epidemiology; Exposure to; Food; Future; General Population; Genes; Genetic; Genetic Variation; Genome; Genomics; Genotype; Grant; Heritability; Hibernation; Hormonal; Human; Impairment; Individual; K-18 conjugate; Knowledge; Laboratories; Lead; Light; Lipids; Mails; Major Depressive Disorder; Mammals; Measurement; Measures; Melatonin; Mental Depression; Mentors; Mentorship; Mission; Modeling; Monitor; Mood Disorders; Moods; National Institute of Mental Health; Nature; Neurologic; Occupational; Participant; Pathway interactions; Patients; Pattern; Perception; Physiological; Physiology; Population; Questionnaires; Recurrence; Reporting; Research; Running; Sampling; Seasonal Affective Disorder; Seasonal Variations; Seasons; Sleep; Social Functioning; Stress; Symptoms; Syndrome; Temperature; Testing; Time; Translating; Twin Multiple Birth; Twin Studies; Weight; Weight Gain; Work; base; cardiovascular risk factor; cohort; craving; depressive symptoms; design; dysphoria; falls; gene environment interaction; genetic epidemiology; genome wide association study; glucose metabolism; increased appetite; melanopsin; migration; mortality; novel; prospective; psychosocial; public health priorities; reproductive; response; sex; skills; social; suicidal behavior

DESCRIPTION (provided by applicant): In response to and in anticipation of seasonal changes in natural- light, many animals manifest marked seasonal changes in physiology and behavior, such as those related to hibernation, breeding and migration. Although humans have increasingly (but far from completely) isolated themselves from the natural environment, certain individuals manifest seasonal changes in mood and behavior, though to more modest degree than in photoperiodic animals. Some patients with recurrent mood disorders develop full major depression syndromes in the fall or winter, with full remission in spring or summer, a condition called seasonal affective disorder winter type (SAD). SAD is a condition associated with an intermittent but significant impairment in occupational, academic and social functioning. Although psychosocial difficulties in fall and winter are in the immediate picture for professionals treating SAD, the biological nature of this condition is underscored by similarities in certain SAD symptoms with season-specific behavioral changes in photoperiodic mammals (environment disengagement, increased appetite, weight and sleepiness, reduced energy and reproductive drive)24, the effectiveness of timed bright light exposure in treating SAD27-30, and an extended duration in winter of nocturnal melatonin secretion in SAD patients (but not in controls) as in photoperiodic mammals1 A previous twin study on seasonality using the Seasonal Pattern Assessment Questionnaire (SPAQ) that gives a global seasonality score (GSS) has reported that the heritability of seasonality of mood is 29%% 2. The long term objective of the PI is to study precipitating and perpetuating factors in the physical, chemical and biological environment exacerbating mood disorders in predisposed individuals, and more specifically to identify trigger- vulnerability pairs for seasonal disturbances in mood and behavior. The short term objective of this project is to identify genetic variations that are associated with seasonality of mood. We will mail the SPAQ to 1800 Amish participants previously genotyped for the 500K or 1 M Affymetrics SNP chip. GSS levels, logarithm-transformed and adjusted for age and sex, will be analyzed for heritability and screened for association with SNPs using mixed model variance components to account for familial relatedness. The "top hits" will then be replicated in 1,000 Amish participants in whom DNA is immediately available. The questionnaire response rate is expected to exceed 80%, based on long standing partnership between the research team and the Amish. This study will be novel in both genetic and environmental epidemiology domains; genetically this will be the first GWAS of mood seasonality, and environmentally, the first study of seasonality of mood in a population that predominantly does not use electricity, thus, with greater exposure and tuning to natural photoperiodic changes. The project is expected to contribute to designing future studies on SAD, with prospective measurements of mood and light exposure, in interaction with emerging candidate genes. This may lead to further studies that may ultimately result in individualized treatment of SAD, as well as potentially advance our knowledge on mechanisms leading to seasonal variation in mood, behavior and cardiovascular risk factors, such as weight, cholesterol, and immune mediators, suspected to contribute to increased cardiovascular mortality in the winter. PUBLIC HEALTH RELEVANCE: Seasonal affective disorder, also called SAD /winter depression, is a serious condition that affects millions of Americans; we propose to perform obtain a score of mood seasonality in 1000 Amish subjects who had their full genome previously analyzed for another study and whose customs do not allow use of electricity reducing exposure to artificial light in winter and use of air conditioners in summer. In line with the mission of K18, This grant will help the applicant to become fluent with full genome approaches that will add a major capability to his ongoing exploration of vulnerabilities to environmental triggers in mood disorders and suicidal behavior, domains of public health priority. The study will be the first genomic study on seasonality of mood, and first seasonality study in the US in a population not using electric light.

描述（由申请人提供）：响应于和预期自然光的季节性变化，许多动物在生理和行为上表现出明显的季节性变化，例如与冬眠、繁殖和迁移有关的季节性变化。虽然人类越来越多地（但远未完全）将自己与自然环境隔离，但某些个体在情绪和行为上表现出季节性变化，尽管程度比光周期动物更温和。一些复发性心境障碍患者在秋季或冬季发展为完全的重度抑郁综合征，在春季或夏季完全缓解，这种情况称为季节性情感障碍冬季型（SAD）。SAD是一种与职业、学术和社会功能间歇性但显著受损相关的疾病。虽然心理社会的困难，在秋季和冬季是在直接图片的专业人员治疗SAD，这种情况的生物学性质是强调了相似性，在某些SAD症状与季节特异性行为变化的光周期哺乳动物（脱离环境，食欲、体重和嗜睡增加，能量和生殖驱动力降低）24、定时强光暴露在治疗SAD中的有效性27 -30，在SAD患者中（但不是在对照组中），冬季夜间褪黑激素分泌的持续时间延长，如在光周期性哺乳动物中1。先前使用季节性模式评估问卷（SPAQ）进行的关于季节性的双胞胎研究给出了总体季节性评分（GSS），该研究报告了情绪季节性的遗传性为29%2。PI的长期目标是研究物理、化学和生物环境中加剧易感个体情绪障碍的诱发和持续因素，更具体地说，是确定情绪和行为季节性紊乱的触发-脆弱性对。该项目的短期目标是确定与情绪季节性相关的遗传变异。我们将把SPAQ邮寄给1800名先前用500 K或1 M Affymetrics SNP芯片进行基因分型的阿米什人参与者。将分析GSS水平的遗传性，并使用混合模型方差分量筛选与SNP的相关性，以解释家族相关性。然后将在1 000名阿米什人参与者中复制“最热门”，这些参与者的DNA立即可用。基于研究团队与阿米什人之间的长期合作关系，问卷答复率预计将超过80%。这项研究在遗传和环境流行病学领域都是新颖的;从遗传学上讲，这将是第一个情绪季节性的GWAS，从环境上讲，这是第一个在主要不用电的人群中研究情绪季节性的研究，因此，有更多的暴露和调整自然光周期变化。该项目预计将有助于设计未来的SAD研究，通过对情绪和光照的前瞻性测量，与新兴的候选基因相互作用。这可能会导致进一步的研究，最终可能导致SAD的个体化治疗，并可能提高我们对导致情绪，行为和心血管风险因素（如体重，胆固醇和免疫介质）季节性变化的机制的认识，这些因素可能导致冬季心血管死亡率增加。 公共卫生相关性：季节性情感障碍，也称为SAD /冬季抑郁症，是一种影响数百万美国人的严重疾病;我们建议在1000名阿米什人受试者中进行情绪季节性评分，这些受试者之前曾为另一项研究分析过他们的全基因组，并且他们的习俗不允许使用电力，冬季减少暴露于人造光，夏季使用空调。根据K18的使命，这笔赠款将帮助申请人成为流利的全基因组方法，这将增加一个主要的能力，他正在进行的探索脆弱性的环境触发情绪障碍和自杀行为，公共卫生优先领域.这项研究将是第一项关于情绪季节性的基因组研究，也是美国第一项针对不使用电灯的人群的季节性研究。

项目成果

Seasonality of mood and behavior in the Old Order Amish.

旧秩序阿米什人情绪和行为的季节性。

• DOI: 10.1016/j.jad.2012.10.019
• 发表时间: 2013
• 期刊: Journal of affective disorders
• 影响因子: 6.6
• 作者: Raheja,UttamK;Stephens,SarahH;Mitchell,BraxtonD;Rohan,KellyJ;Vaswani,Dipika;Balis,TheodoraG;Nijjar,GaganV;Sleemi,Aamar;Pollin,ToniI;Ryan,Kathleen;Reeves,GloriaM;Weitzel,Nancy;Morrissey,Mary;Yousufi,Hassaan;Langenberg,P
• 通讯作者: Langenberg,P