American Journal of Medical Genetics Part B: Neuropsychiatric Genetics最新文献_第2页

Sex Differences in Cortical Thickness and Neuropsychiatric Symptom Burden Based on APOE4 Homozygosity in Alzheimer's Disease. 基于阿尔茨海默病 APOE4 基因同源性的皮质厚度和神经精神症状负担的性别差异。

IF 1.6 3区医学

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Pub Date : 2024-09-30 DOI: 10.1002/ajmg.b.33008

Marc A Khoury, Mila Valcic, Nathan W Churchill, Alex Di Battista, Vincenzo De Luca, Luis R Fornazzari, David G Munoz, Corinne E Fischer, Tom A Schweizer

{"title":"Sex Differences in Cortical Thickness and Neuropsychiatric Symptom Burden Based on APOE4 Homozygosity in Alzheimer's Disease.","authors":"Marc A Khoury, Mila Valcic, Nathan W Churchill, Alex Di Battista, Vincenzo De Luca, Luis R Fornazzari, David G Munoz, Corinne E Fischer, Tom A Schweizer","doi":"10.1002/ajmg.b.33008","DOIUrl":"https://doi.org/10.1002/ajmg.b.33008","url":null,"abstract":"Sex differences in patterns of cortical thickness and neuropsychiatric symptom (NPS) burden were examined among individuals with Alzheimer's disease (AD) and two copies (homozygote carriers) of the e4 allele of the apolipoprotein gene (APOE). A total of 752 participants with a clinical etiologic diagnosis of AD were selected from the National Alzheimer's Coordinating Center (NACC) database. Bayesian multilevel regression was used to examine both the within- and between-sex differences in gray-matter cortical thickness and total NPS burden associated with APOE homozygosity. Female homozygote carriers displayed a high probability of having reduced cortical thickness primarily in medial-lateral temporal regions and a greater burden of NPS, relative to both non-homozygous females and homozygous males. These findings support the notion that APOE4 status affects cortical thickness and symptom burden in men and women with AD differentially, with females showing more pronounced effects in brain areas known to be vulnerable in early AD. Future investigations should attempt to elucidate the proposed pattern of decline longitudinally.","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":" ","pages":"e33008"},"PeriodicalIF":1.6,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Parenting Stress Index in Caregivers of Individuals With Noonan Syndrome. 努南综合征患者照顾者的养育压力指数。

IF 1.6 3区医学

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Pub Date : 2024-09-27 DOI: 10.1002/ajmg.b.33009

Lucrezia Perri, Germana Viscogliosi, Valentina Trevisan, Claudia Brogna, Daniela Pia Rosaria Chieffo, Ilaria Contaldo, Paolo Alfieri, Nicolo' Lentini, Roberta Pastorino, Giuseppe Zampino, Chiara Leoni

{"title":"Parenting Stress Index in Caregivers of Individuals With Noonan Syndrome.","authors":"Lucrezia Perri, Germana Viscogliosi, Valentina Trevisan, Claudia Brogna, Daniela Pia Rosaria Chieffo, Ilaria Contaldo, Paolo Alfieri, Nicolo' Lentini, Roberta Pastorino, Giuseppe Zampino, Chiara Leoni","doi":"10.1002/ajmg.b.33009","DOIUrl":"https://doi.org/10.1002/ajmg.b.33009","url":null,"abstract":"Medical professionals frequently underestimate stress level of parents/caregivers of patients with rare disorders as RASopathies, the latter might experience elevated stress levels, with their own health frequently overlooked despite significant responsibilities and hurdles encountered. The aim of this study is to assess the stress experienced by parents of individuals with Noonan syndrome and related conditions. Forty-eight parents (20 fathers; 28 mothers), among the 31 recruited families, completed the Italian version of the Parenting Stress Index-Short Form. Our study shows abnormally elevated scores (≥ 85° percentile) in 35.4% of parents. Data retrieved from subscales reveal a perception of a difficult child in 25% of cases, a dysfunctional parental-child interaction in 20.8%, a general parental distress in 10.4% of cases, and an elevated overall stress in 18.8% of parents. Questionnaires as the Parenting Stress Index-Short Form are valuable tools to evaluate stress in parents/caregivers of children with RASopathies. Evaluation by professionals is fundamental to support parents and caregivers in managing stressors and to enhance their quality of life and relationships. To prevent stress escalation and parents' burnout, an early assessment to tailor a timely treatment should be introduced as soon as possible as good clinical practice.","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":" ","pages":"e33009"},"PeriodicalIF":1.6,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cognitive, Social, and Emotional-Behavioral Outcomes in Children and Adolescents With Beckwith-Wiedemann Syndrome. 贝克维茨-韦德曼综合症儿童和青少年的认知、社交和情感行为结果。

IF 1.6 3区医学

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Pub Date : 2024-09-25 DOI: 10.1002/ajmg.b.33006

Niccolò Butti, Cosimo Urgesi, Alessandro Mussa, Rosario Montirosso

{"title":"Cognitive, Social, and Emotional-Behavioral Outcomes in Children and Adolescents With Beckwith-Wiedemann Syndrome.","authors":"Niccolò Butti, Cosimo Urgesi, Alessandro Mussa, Rosario Montirosso","doi":"10.1002/ajmg.b.33006","DOIUrl":"https://doi.org/10.1002/ajmg.b.33006","url":null,"abstract":"Although Beckwith-Wiedemann syndrome spectrum (BWSp) is not usually associated with intellectual disability, recent evidences calls for further investigation of cognitive development and academic skills in children with BWSp. Moreover, research has documented social difficulties and emotional-behavioral problems associated with BWSp. Nevertheless, a full characterization of socio-emotional development in BWSp is still lacking. In the current study, cognitive and socio-emotional development was assessed in 29 children with BWSp aged 5-18 years, using a test of nonverbal intelligence, a neuropsychological battery covering multiple domains, academic skills tests, and questionnaires evaluating autistic traits and emotional-behavioral problems. As expected, most participants showed adequate performance in cognitive tests. However, the findings also highlighted greater difficulties in language than visuospatial processing, strengths in social perception, as well as slowness in reading and mental calculation. The assessment of emotional-behavioral difficulties indicated a prevalent phenotype characterized by increased anxiety, low self-esteem, social withdrawal and a tendency to control externalizing reactions, but no associations with autistic traits, cognitive outcomes, and the clinical score proposed by the recent Consensus statement. Increased social perception and internalization problems likely result from coping strategies with social and care-related stress. Overall, the findings of this study inform clinical management and genetic counseling for children and adolescents with BWSp.","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":" ","pages":"e33006"},"PeriodicalIF":1.6,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Circadian Rhythms Correlated in DNA Methylation and Gene Expression Identified in Human Blood and Implicated in Psychiatric Disorders 在人体血液中发现与 DNA 甲基化和基因表达相关的昼夜节律，并与精神疾病有关。

IF 1.6 3区医学

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Pub Date : 2024-09-25 DOI: 10.1002/ajmg.b.33005

Haiyan Tang, Shanshan Chen, Liu Yi, Sheng Xu, Huihui Yang, Zongchang Li, Ying He, Yanhui Liao, Xiaogang Chen, Chunyu Liu, Lin Gu, Ning Yuan, Chao Chen, Jinsong Tang

{"title":"Circadian Rhythms Correlated in DNA Methylation and Gene Expression Identified in Human Blood and Implicated in Psychiatric Disorders","authors":"Haiyan Tang, Shanshan Chen, Liu Yi, Sheng Xu, Huihui Yang, Zongchang Li, Ying He, Yanhui Liao, Xiaogang Chen, Chunyu Liu, Lin Gu, Ning Yuan, Chao Chen, Jinsong Tang","doi":"10.1002/ajmg.b.33005","DOIUrl":"10.1002/ajmg.b.33005","url":null,"abstract":"<div>\u0000 \u0000 Circadian rhythms modulate the biology of many human tissues and are driven by a nearly 24-h transcriptional feedback loop. Dynamic DNA methylation may play a role in driving 24-h rhythms of gene expression in the human brain. However, little is known about the degree of circadian regulation between the DNA methylation and the gene expression in the peripheral tissues, including human blood. We hypothesized that 24-h rhythms of DNA methylation play a role in driving 24-h RNA expression in human blood. To test this hypothesis, we analyzed DNA methylation levels and RNA expression in blood samples collected from eight healthy males at six-time points over 24 h. We assessed 442,703 genome-wide CpG sites in methylation and 12,364 genes in expression for 24-h rhythmicity using the cosine model. Our analysis revealed significant rhythmic patterns in 6345 CpG sites and 21 genes. Next, we investigated the relationship between methylation and expression using powerful circadian signals. We found a modest negative correlation (ρ = −0.83, p = 0.06) between the expression of gene TXNDC5 and the methylation at the nearby CpG site (cg19116172). We also observed that circadian CpGs significantly overlapped with genetic risk loci of schizophrenia and autism spectrum disorders. Notably, one gene, TXNDC5, showed a significant correlation between circadian methylation and expression and has been reported to be association with neuropsychiatric diseases.\u0000 </div>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"198 1","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Associations of Polygenic Risk for Depression, Traditional Chinese Medicine Constitution, and Depression: A Population-Based Study in Taiwan 抑郁症多基因风险、中医体质与抑郁症的关联：基于台湾人口的研究

IF 1.6 3区医学

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Pub Date : 2024-09-10 DOI: 10.1002/ajmg.b.33007

Yu-Cheng Hsu, Mei-Hsin Su, Chia-Yen Chen, Yen-Feng Lin, Shi-Heng Wang

{"title":"Associations of Polygenic Risk for Depression, Traditional Chinese Medicine Constitution, and Depression: A Population-Based Study in Taiwan","authors":"Yu-Cheng Hsu, Mei-Hsin Su, Chia-Yen Chen, Yen-Feng Lin, Shi-Heng Wang","doi":"10.1002/ajmg.b.33007","DOIUrl":"10.1002/ajmg.b.33007","url":null,"abstract":"<div>\u0000 \u0000 To comprehensively investigate the risk factors associated with depression, traditional Chinese medicine constitution (TCMC) has been found to be related to depression. However, the underlying mechanism remains unclear. This study examined the association between the concept of unbalanced TCMCs and major depressive disorder (MDD), investigated the overlapping polygenic risks between unbalanced TCMC and MDD, and performed a mediation test to establish potential pathways. In total, 11,030 individuals were recruited from the Taiwan Biobank, and the polygenic risk score (PRS) for MDD for each participant was calculated using the data from the Psychiatric Genomics Consortium. Unbalanced TCMC were classified as yang-deficiency, yin-deficiency, and stasis. The MDD PRS was associated with yang-deficiency odds ratio [OR] per standard deviation increase in standardized (PRS = 1.07, p = 0.0080), yin-deficiency (OR = 1.07, p = 0.0030), and stasis constitution (OR = 1.06, p = 0.0331). Yang-deficiency (OR = 2.07, p < 0.0001) and stasis constitutions (OR = 1.65, p = 0.0015) were associated with an increased risk of MDD. A higher number of unbalanced constitutions was associated with MDD (p < 0.0001). The effect of MDD PRS on MDD was partly mediated by yang-deficiency (10.21%) and stasis (8.41%) constitutions. This study provides evidence for the shared polygenic risk mechanism underlying depression and TCMC and the potential mediating role of TCMC in the polygenic liability for MDD.\u0000 </div>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"198 1","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142217419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The genetic and environmental etiology of novel frequency-driven regional parcellations of abnormal white matter 新频率驱动的区域性异常白质小片的遗传和环境病因。

IF 1.6 3区医学

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Pub Date : 2024-08-16 DOI: 10.1002/ajmg.b.33004

Shu-Ju Lin, Nathan A. Gillespie, Randy Notestine, Anthony C. Gamst, Anna M. Chen, Linda K. McEvoy, Matthew S. Panizzon, Jeremy A. Elman, Stephen J. Glatt, Donald J. Hagler Jr, Michael C. Neale, Carol E. Franz, William S. Kremen, Christine Fennema-Notestine

{"title":"The genetic and environmental etiology of novel frequency-driven regional parcellations of abnormal white matter","authors":"Shu-Ju Lin, Nathan A. Gillespie, Randy Notestine, Anthony C. Gamst, Anna M. Chen, Linda K. McEvoy, Matthew S. Panizzon, Jeremy A. Elman, Stephen J. Glatt, Donald J. Hagler Jr, Michael C. Neale, Carol E. Franz, William S. Kremen, Christine Fennema-Notestine","doi":"10.1002/ajmg.b.33004","DOIUrl":"10.1002/ajmg.b.33004","url":null,"abstract":"The prevalence of white matter disease increases with age and is associated with cerebrovascular disease, cognitive decline, and risk for dementia. MRI measures of abnormal signal in the white matter (AWM) provide estimates of damage, however, regional patterns of AWM may be differentially influenced by genetic or environmental factors. With our data-driven regional parcellation approach, we created a probability distribution atlas using Vietnam Era Twin Study of Aging (VETSA) data (n = 475, mean age 67.6 years) and applied a watershed algorithm to define separate regional parcellations. We report biometrical twin modeling for five anatomically distinct regions: (1) Posterior, (2) Superior frontal and parietal, (3) Anterior and inferior frontal with deep areas, (4) Occipital, and (5) Anterior periventricular. We tested competing multivariate hypotheses to identify unique influences and to explain sources of covariance among the parcellations. Family aggregation could be entirely explained by additive genetic influences, with additive genetic variance (heritability) ranging from 0.69 to 0.79. Most genetic correlations between parcellations ranged from moderate to high (rg = 0.57–0.85), although two were small (rg = 0.35–0.39), consistent with varying degrees of unique genetic influences. This proof-of-principle investigation demonstrated the value of our novel, data-driven parcellations, with identifiable genetic and environmental differences, for future exploration.","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"198 1","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A twin analysis to estimate genetic and environmental factors contributing to variation in weighted gene co-expression network module eigengenes 通过孪生子分析估算导致加权基因共表达网络模块eigengenes变异的遗传和环境因素。

IF 1.6 3区医学

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Pub Date : 2024-08-09 DOI: 10.1002/ajmg.b.33003

Nathan A. Gillespie, Tyler R. Bell, Gentry C. Hearn, Jonathan L. Hess, Ming T. Tsuang, Michael J. Lyons, Carol E. Franz, William S. Kremen, Stephen J. Glatt

{"title":"A twin analysis to estimate genetic and environmental factors contributing to variation in weighted gene co-expression network module eigengenes","authors":"Nathan A. Gillespie, Tyler R. Bell, Gentry C. Hearn, Jonathan L. Hess, Ming T. Tsuang, Michael J. Lyons, Carol E. Franz, William S. Kremen, Stephen J. Glatt","doi":"10.1002/ajmg.b.33003","DOIUrl":"10.1002/ajmg.b.33003","url":null,"abstract":"Multivariate network-based analytic methods such as weighted gene co-expression network analysis are frequently applied to human and animal gene-expression data to estimate the first principal component of a module, or module eigengene (ME). MEs are interpreted as multivariate summaries of correlated gene-expression patterns and network connectivity across genes within a module. As such, they have the potential to elucidate the mechanisms by which molecular genomic variation contributes to individual differences in complex traits. Although increasingly used to test for associations between modules and complex traits, the genetic and environmental etiology of MEs has not been empirically established. It is unclear if, and to what degree, individual differences in blood-derived MEs reflect random variation versus familial aggregation arising from heritable or shared environmental influences. We used biometrical genetic analyses to estimate the contribution of genetic and environmental influences on MEs derived from blood lymphocytes collected on a sample of N = 661 older male twins from the Vietnam Era Twin Study of Aging (VETSA) whose mean age at assessment was 67.7 years (SD = 2.6 years, range = 62–74 years). Of the 26 detected MEs, 14 (56%) had statistically significant additive genetic variation with an average heritability of 44% (SD = 0.08, range = 35%–64%). Despite the relatively small sample size, this demonstration of significant family aggregation including estimates of heritability in 14 of the 26 MEs suggests that blood-based MEs are reliable and merit further exploration in terms of their associations with complex traits and diseases.","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"198 1","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.b.33003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141911301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring the genetic architecture of brain structure and ADHD using polygenic neuroimaging-derived scores 利用多基因神经成像衍生评分探索大脑结构和多动症的遗传结构。

IF 1.6 3区医学

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Pub Date : 2024-07-17 DOI: 10.1002/ajmg.b.32987

Tim van der Es, Sourena Soheili-Nezhad, Nina Roth Mota, Barbara Franke, Jan Buitelaar, Emma Sprooten

{"title":"Exploring the genetic architecture of brain structure and ADHD using polygenic neuroimaging-derived scores","authors":"Tim van der Es, Sourena Soheili-Nezhad, Nina Roth Mota, Barbara Franke, Jan Buitelaar, Emma Sprooten","doi":"10.1002/ajmg.b.32987","DOIUrl":"10.1002/ajmg.b.32987","url":null,"abstract":"Genome-wide association studies (GWAS) have provided valuable insights into the genetic basis of neuropsychiatric disorders and highlighted their complexity. Careful consideration of the polygenicity and complex genetic architecture could aid in the understanding of the underlying brain mechanisms. We introduce an innovative approach to polygenic scoring, utilizing imaging-derived phenotypes (IDPs) to predict a clinical phenotype. We leveraged IDP GWAS data from the UK Biobank, to create polygenic imaging-derived scores (PIDSs). As a proof-of-concept, we assessed genetic variations in brain structure between individuals with ADHD and unaffected controls across three NeuroIMAGE waves (n = 954). Out of the 94 PIDS, 72 exhibited significant associations with their corresponding IDPs in an independent sample. Notably, several global measures, including cerebellum white matter, cerebellum cortex, and cerebral white matter, displayed substantial variance explained for their respective IDPs, ranging from 3% to 5.7%. Conversely, the associations between each IDP and the clinical ADHD phenotype were relatively weak. These findings highlight the growing power of GWAS in structural neuroimaging traits, enabling the construction of polygenic scores that accurately reflect the underlying polygenic architecture. However, to establish robust connections between PIDS and behavioral or clinical traits such as ADHD, larger samples are needed. Our novel approach to polygenic risk scoring offers a valuable tool for researchers in the field of psychiatric genetics.","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"198 1","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.b.32987","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141625720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Independent inheritance of cognition and bipolar disorder in a family sample 家族样本中认知和躁郁症的独立遗传。

IF 1.6 3区医学

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Pub Date : 2024-07-16 DOI: 10.1002/ajmg.b.33001

Alexander D'Amico, Heejong Sung, Alejandro Arbona-Lampaya, Ally Freifeld, Katie Hosey, Joshua Garcia, Ley Lacbawan, Emily Besançon, Layla Kassem, Nirmala Akula, Emma E. M. Knowles, Dwight Dickinson, Francis J. McMahon

{"title":"Independent inheritance of cognition and bipolar disorder in a family sample","authors":"Alexander D'Amico, Heejong Sung, Alejandro Arbona-Lampaya, Ally Freifeld, Katie Hosey, Joshua Garcia, Ley Lacbawan, Emily Besançon, Layla Kassem, Nirmala Akula, Emma E. M. Knowles, Dwight Dickinson, Francis J. McMahon","doi":"10.1002/ajmg.b.33001","DOIUrl":"10.1002/ajmg.b.33001","url":null,"abstract":"Cognitive deficits in people with bipolar disorder (BD) may be the result of the illness or its treatment, but they could also reflect genetic risk factors shared between BD and cognition. We investigated this question using empirical genetic relationships within a sample of patients with BD and their unaffected relatives. Participants with bipolar I, II, or schizoaffective disorder (“narrow” BD, n = 69), related mood disorders (“broad” BD, n = 135), and their clinically unaffected relatives (n = 227) completed five cognitive tests. General cognitive function (g) was quantified via principal components analysis (PCA). Heritability and genetic correlations were estimated with SOLAR-Eclipse. Participants with “narrow” or “broad” diagnoses showed deficits in g, although affect recognition was unimpaired. Cognitive performance was significantly heritable (h2 = 0.322 for g, p < 0.005). Coheritability between psychopathology and g was small (0.0184 for narrow and 0.0327 for broad) and healthy relatives of those with BD were cognitively unimpaired. In this family sample, cognitive deficits were present in participants with BD but were not explained by substantial overlaps in genetic determinants of mood and cognition. These findings support the view that cognitive deficits in BD are largely the result of the illness or its treatment.","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"198 1","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.b.33001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Polygene by environment interactions predicting depressive outcomes 多基因与环境的相互作用可预测抑郁的结果。

IF 1.6 3区医学

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Pub Date : 2024-07-16 DOI: 10.1002/ajmg.b.33000

Alessandra R. Grillo

{"title":"Polygene by environment interactions predicting depressive outcomes","authors":"Alessandra R. Grillo","doi":"10.1002/ajmg.b.33000","DOIUrl":"10.1002/ajmg.b.33000","url":null,"abstract":"Depression is a major public health problem with a continued need to uncover its etiology. Current models of depression contend that gene-by-environment (G × E) interactions influence depression risk, and further, that depression is polygenic. Thus, recent models have emphasized two polygenic approaches: a hypothesis-driven multilocus genetic profile score (MGPS; “MGPS × E”) and a polygenic risk score (PRS; “PRS × E”) derived from genome-wide association studies (GWAS). This review for the first time synthesizes current knowledge on polygene by environment “P × E” interaction research predicting primarily depression-related outcomes, and in brief, neurobiological outcomes. The “environment” of focus in this project is stressful life events. It further discusses findings in the context of differential susceptibility and diathesis-stress theories—two major theories guiding G × E work. This synthesis indicates that, within the MGPS literature, polygenic scores based on the serotonin system, the HPA axis, or across multiple systems, interact with environmental stress exposure to predict outcomes at multiple levels of analyses and most consistently align with differential susceptibility theory. Depressive outcomes are the most studied, but neuroendocrine, and neuroimaging findings are observed as well. By contrast, vast methodological differences between GWAS-based PRS studies contribute to mixed findings that yield inconclusive results.","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"198 1","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.b.33000","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0