Alejandro Arbona-Lampaya, Heejong Sung, Alexander D'Amico, Emma E M Knowles, Emily K Besançon, Ally Freifeld, Ley Lacbawan, Fabiana Lopes, Layla Kassem, Antonio E Nardi, Francis J McMahon
{"title":"家庭样本中双相情感障碍的遗传性、表型和遗传相关性的维度和分类模型。","authors":"Alejandro Arbona-Lampaya, Heejong Sung, Alexander D'Amico, Emma E M Knowles, Emily K Besançon, Ally Freifeld, Ley Lacbawan, Fabiana Lopes, Layla Kassem, Antonio E Nardi, Francis J McMahon","doi":"10.1016/j.jad.2024.12.030","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Bipolar disorder (BD) presents with a wide range of symptoms that vary among relatives, casting doubt on categorical illness models. To address this uncertainty, we investigated the heritability and genetic relationships between categorical and dimensional models of BD in a family sample.</p><p><strong>Methods: </strong>This retrospective study included participants (n = 397 Females, n = 329 Males, mean age 47 yr) in the Amish-Mennonite Bipolar Genetics (AMBiGen) study from North and South America that were assigned categorical mood disorder diagnoses (\"narrow\" or \"broad\") by structured psychiatric interview and completed the Mood Disorder Questionnaire (MDQ), which assesses lifetime history of manic symptoms and associated impairment. MDQ-dimensions were analyzed by Principal Component Analysis (PCA). Heritability and genetic overlaps between categorical diagnoses and MDQ-dimensions were estimated with SOLAR-ECLIPSE within 432 genotyped participants.</p><p><strong>Results: </strong>Individuals diagnosed with BD (n = 124) endorsed more MDQ items (61 %) than those with other mood disorders (26 %) or with no mood disorder (9 %), as expected. PCA suggested a three-component model for the MDQ, capturing 60 % of the variance. Heritability of the MDQ and its principal components was significant but modest (20-30 %, p < 0.001). Genetic correlations between MDQ measures and categorical diagnoses (ρG = 0.62-1.0; p < 0.001) were stronger than phenotypic correlations (ρP = 0.11-0.58; p < 0.001).</p><p><strong>Limitations: </strong>Recruitment through probands with BD resulted in increased prevalence of BD in this sample, limiting generalizability. Unavailable genetic data reduced sample size for some analyses.</p><p><strong>Conclusion: </strong>Findings support a genetic continuity between dimensional and categorical models of BD and suggest that the MDQ is a useful phenotype measure for genetic studies of BD.</p>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":" ","pages":"394-401"},"PeriodicalIF":4.9000,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Heritability, phenotypic, and genetic correlations across dimensional and categorical models of bipolar disorder in a family sample.\",\"authors\":\"Alejandro Arbona-Lampaya, Heejong Sung, Alexander D'Amico, Emma E M Knowles, Emily K Besançon, Ally Freifeld, Ley Lacbawan, Fabiana Lopes, Layla Kassem, Antonio E Nardi, Francis J McMahon\",\"doi\":\"10.1016/j.jad.2024.12.030\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Bipolar disorder (BD) presents with a wide range of symptoms that vary among relatives, casting doubt on categorical illness models. To address this uncertainty, we investigated the heritability and genetic relationships between categorical and dimensional models of BD in a family sample.</p><p><strong>Methods: </strong>This retrospective study included participants (n = 397 Females, n = 329 Males, mean age 47 yr) in the Amish-Mennonite Bipolar Genetics (AMBiGen) study from North and South America that were assigned categorical mood disorder diagnoses (\\\"narrow\\\" or \\\"broad\\\") by structured psychiatric interview and completed the Mood Disorder Questionnaire (MDQ), which assesses lifetime history of manic symptoms and associated impairment. MDQ-dimensions were analyzed by Principal Component Analysis (PCA). Heritability and genetic overlaps between categorical diagnoses and MDQ-dimensions were estimated with SOLAR-ECLIPSE within 432 genotyped participants.</p><p><strong>Results: </strong>Individuals diagnosed with BD (n = 124) endorsed more MDQ items (61 %) than those with other mood disorders (26 %) or with no mood disorder (9 %), as expected. PCA suggested a three-component model for the MDQ, capturing 60 % of the variance. Heritability of the MDQ and its principal components was significant but modest (20-30 %, p < 0.001). Genetic correlations between MDQ measures and categorical diagnoses (ρG = 0.62-1.0; p < 0.001) were stronger than phenotypic correlations (ρP = 0.11-0.58; p < 0.001).</p><p><strong>Limitations: </strong>Recruitment through probands with BD resulted in increased prevalence of BD in this sample, limiting generalizability. Unavailable genetic data reduced sample size for some analyses.</p><p><strong>Conclusion: </strong>Findings support a genetic continuity between dimensional and categorical models of BD and suggest that the MDQ is a useful phenotype measure for genetic studies of BD.</p>\",\"PeriodicalId\":14963,\"journal\":{\"name\":\"Journal of affective disorders\",\"volume\":\" \",\"pages\":\"394-401\"},\"PeriodicalIF\":4.9000,\"publicationDate\":\"2024-12-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of affective disorders\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jad.2024.12.030\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of affective disorders","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jad.2024.12.030","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Heritability, phenotypic, and genetic correlations across dimensional and categorical models of bipolar disorder in a family sample.
Background: Bipolar disorder (BD) presents with a wide range of symptoms that vary among relatives, casting doubt on categorical illness models. To address this uncertainty, we investigated the heritability and genetic relationships between categorical and dimensional models of BD in a family sample.
Methods: This retrospective study included participants (n = 397 Females, n = 329 Males, mean age 47 yr) in the Amish-Mennonite Bipolar Genetics (AMBiGen) study from North and South America that were assigned categorical mood disorder diagnoses ("narrow" or "broad") by structured psychiatric interview and completed the Mood Disorder Questionnaire (MDQ), which assesses lifetime history of manic symptoms and associated impairment. MDQ-dimensions were analyzed by Principal Component Analysis (PCA). Heritability and genetic overlaps between categorical diagnoses and MDQ-dimensions were estimated with SOLAR-ECLIPSE within 432 genotyped participants.
Results: Individuals diagnosed with BD (n = 124) endorsed more MDQ items (61 %) than those with other mood disorders (26 %) or with no mood disorder (9 %), as expected. PCA suggested a three-component model for the MDQ, capturing 60 % of the variance. Heritability of the MDQ and its principal components was significant but modest (20-30 %, p < 0.001). Genetic correlations between MDQ measures and categorical diagnoses (ρG = 0.62-1.0; p < 0.001) were stronger than phenotypic correlations (ρP = 0.11-0.58; p < 0.001).
Limitations: Recruitment through probands with BD resulted in increased prevalence of BD in this sample, limiting generalizability. Unavailable genetic data reduced sample size for some analyses.
Conclusion: Findings support a genetic continuity between dimensional and categorical models of BD and suggest that the MDQ is a useful phenotype measure for genetic studies of BD.
期刊介绍:
The Journal of Affective Disorders publishes papers concerned with affective disorders in the widest sense: depression, mania, mood spectrum, emotions and personality, anxiety and stress. It is interdisciplinary and aims to bring together different approaches for a diverse readership. Top quality papers will be accepted dealing with any aspect of affective disorders, including neuroimaging, cognitive neurosciences, genetics, molecular biology, experimental and clinical neurosciences, pharmacology, neuroimmunoendocrinology, intervention and treatment trials.