{"title":"一般疾病与精神障碍遗传相关及因果关系的系统多性状研究","authors":"Ron Nudel, Maria Da Re, Michael E. Benros","doi":"10.1111/acps.13825","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Introduction</h3>\n \n <p>Increasing evidence has highlighted bidirectional associations between mental disorders and general medical conditions, with underlying causes ranging from lifestyle habits and side effects from medications to genetic contributions. Novel methods now provide a way to estimate the shared genetic underpinnings and the possibility of a causal relationship between conditions.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Using summary statistics from large genome-wide association studies of 16 categories of general medical conditions and 12 categories of mental disorders, we estimated pairwise genetic correlations between general medical conditions and mental disorders using LD score regression. For conditions with significant, positive genetic correlations, we used the latent causal variable (LCV) model to assess the evidence for a causal relationship between them.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Ninety-five out of 192 pairs of conditions were significantly genetically correlated (<i>q</i> ≤ 0.05). Strong and significant correlations were found between conditions such as infections and a psychiatric cross-disorder phenotype (<i>r</i><sub>g</sub> = 0.50, <i>p</i> = 1.33 × 10<sup>−6</sup>) and irritable bowel syndrome and depression (<i>r</i><sub>g</sub> = 0.58, <i>p</i> = 1.50 × 10<sup>−16</sup>). In the causality analyses, statistically significant evidence for causality was obtained for seven pairs of conditions, including infections being causal to the psychiatric cross-disorder phenotype, metabolic disorders being causal to attention deficit/hyperactivity disorder (ADHD), post-traumatic stress disorder (PTSD) being causal to bone and cartilage disorders, arthropathies and epilepsy, obsessive–compulsive disorder (OCD) being causal to irritable bowel syndrome (IBS), and ADHD being causal to arthropathies.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>Multiple pairs of general medical conditions and mental disorders were significantly genetically correlated, and for some pairs, there was genetic evidence for a causal relationship. Our findings can inform further molecular studies and clinical practice, raising awareness of the possible co-occurrence of these conditions.</p>\n </section>\n </div>","PeriodicalId":108,"journal":{"name":"Acta Psychiatrica Scandinavica","volume":"152 3","pages":"236-249"},"PeriodicalIF":5.0000,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acps.13825","citationCount":"0","resultStr":"{\"title\":\"Systematic Multi-Trait Study of Genetic Correlation and Causality Relationships Between General Medical Conditions and Mental Disorders\",\"authors\":\"Ron Nudel, Maria Da Re, Michael E. Benros\",\"doi\":\"10.1111/acps.13825\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Introduction</h3>\\n \\n <p>Increasing evidence has highlighted bidirectional associations between mental disorders and general medical conditions, with underlying causes ranging from lifestyle habits and side effects from medications to genetic contributions. Novel methods now provide a way to estimate the shared genetic underpinnings and the possibility of a causal relationship between conditions.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Using summary statistics from large genome-wide association studies of 16 categories of general medical conditions and 12 categories of mental disorders, we estimated pairwise genetic correlations between general medical conditions and mental disorders using LD score regression. For conditions with significant, positive genetic correlations, we used the latent causal variable (LCV) model to assess the evidence for a causal relationship between them.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Ninety-five out of 192 pairs of conditions were significantly genetically correlated (<i>q</i> ≤ 0.05). Strong and significant correlations were found between conditions such as infections and a psychiatric cross-disorder phenotype (<i>r</i><sub>g</sub> = 0.50, <i>p</i> = 1.33 × 10<sup>−6</sup>) and irritable bowel syndrome and depression (<i>r</i><sub>g</sub> = 0.58, <i>p</i> = 1.50 × 10<sup>−16</sup>). In the causality analyses, statistically significant evidence for causality was obtained for seven pairs of conditions, including infections being causal to the psychiatric cross-disorder phenotype, metabolic disorders being causal to attention deficit/hyperactivity disorder (ADHD), post-traumatic stress disorder (PTSD) being causal to bone and cartilage disorders, arthropathies and epilepsy, obsessive–compulsive disorder (OCD) being causal to irritable bowel syndrome (IBS), and ADHD being causal to arthropathies.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>Multiple pairs of general medical conditions and mental disorders were significantly genetically correlated, and for some pairs, there was genetic evidence for a causal relationship. Our findings can inform further molecular studies and clinical practice, raising awareness of the possible co-occurrence of these conditions.</p>\\n </section>\\n </div>\",\"PeriodicalId\":108,\"journal\":{\"name\":\"Acta Psychiatrica Scandinavica\",\"volume\":\"152 3\",\"pages\":\"236-249\"},\"PeriodicalIF\":5.0000,\"publicationDate\":\"2025-05-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acps.13825\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Acta Psychiatrica Scandinavica\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/acps.13825\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PSYCHIATRY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta Psychiatrica Scandinavica","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/acps.13825","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PSYCHIATRY","Score":null,"Total":0}
引用次数: 0
摘要
越来越多的证据强调了精神障碍与一般医疗状况之间的双向关联，其潜在原因包括生活习惯和药物副作用以及遗传因素。新的方法现在提供了一种方法来估计共同的遗传基础和条件之间因果关系的可能性。方法利用16类一般疾病和12类精神障碍的大型全基因组关联研究的汇总统计数据，利用LD评分回归估计一般疾病和精神障碍之间的两两遗传相关性。对于具有显著正遗传相关性的条件，我们使用潜在因果变量（LCV）模型来评估它们之间因果关系的证据。结果192对条件中95对遗传相关显著（q≤0.05）。感染和精神交叉障碍表型（rg = 0.50, p = 1.33 × 10−6）与肠易激综合征和抑郁症（rg = 0.58, p = 1.50 × 10−16）之间存在强烈且显著的相关性。在因果分析中，获得了7对条件的因果关系的统计显著证据，包括感染是精神交叉障碍表型的因果关系，代谢障碍是注意缺陷/多动障碍（ADHD）的因果关系，创伤后应激障碍（PTSD）是骨骼和软骨疾病的因果关系，关节病和癫痫，强迫症（OCD）是肠易激综合征（IBS）的因果关系，以及多动症与关节病的关系结论多对一般疾病与精神障碍存在显著的遗传相关，部分对存在因果关系的遗传证据。我们的发现可以为进一步的分子研究和临床实践提供信息，提高人们对这些疾病可能同时发生的认识。
Systematic Multi-Trait Study of Genetic Correlation and Causality Relationships Between General Medical Conditions and Mental Disorders
Introduction
Increasing evidence has highlighted bidirectional associations between mental disorders and general medical conditions, with underlying causes ranging from lifestyle habits and side effects from medications to genetic contributions. Novel methods now provide a way to estimate the shared genetic underpinnings and the possibility of a causal relationship between conditions.
Methods
Using summary statistics from large genome-wide association studies of 16 categories of general medical conditions and 12 categories of mental disorders, we estimated pairwise genetic correlations between general medical conditions and mental disorders using LD score regression. For conditions with significant, positive genetic correlations, we used the latent causal variable (LCV) model to assess the evidence for a causal relationship between them.
Results
Ninety-five out of 192 pairs of conditions were significantly genetically correlated (q ≤ 0.05). Strong and significant correlations were found between conditions such as infections and a psychiatric cross-disorder phenotype (rg = 0.50, p = 1.33 × 10−6) and irritable bowel syndrome and depression (rg = 0.58, p = 1.50 × 10−16). In the causality analyses, statistically significant evidence for causality was obtained for seven pairs of conditions, including infections being causal to the psychiatric cross-disorder phenotype, metabolic disorders being causal to attention deficit/hyperactivity disorder (ADHD), post-traumatic stress disorder (PTSD) being causal to bone and cartilage disorders, arthropathies and epilepsy, obsessive–compulsive disorder (OCD) being causal to irritable bowel syndrome (IBS), and ADHD being causal to arthropathies.
Conclusions
Multiple pairs of general medical conditions and mental disorders were significantly genetically correlated, and for some pairs, there was genetic evidence for a causal relationship. Our findings can inform further molecular studies and clinical practice, raising awareness of the possible co-occurrence of these conditions.
期刊介绍：
Acta Psychiatrica Scandinavica acts as an international forum for the dissemination of information advancing the science and practice of psychiatry. In particular we focus on communicating frontline research to clinical psychiatrists and psychiatric researchers.
Acta Psychiatrica Scandinavica has traditionally been and remains a journal focusing predominantly on clinical psychiatry, but translational psychiatry is a topic of growing importance to our readers. Therefore, the journal welcomes submission of manuscripts based on both clinical- and more translational (e.g. preclinical and epidemiological) research. When preparing manuscripts based on translational studies for submission to Acta Psychiatrica Scandinavica, the authors should place emphasis on the clinical significance of the research question and the findings. Manuscripts based solely on preclinical research (e.g. animal models) are normally not considered for publication in the Journal.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
