American Journal of Medical Genetics Part B: Neuropsychiatric Genetics最新文献_第8页

The examination of Kraepelin's diagnoses of dementia praecox and manic-depressive insanity in pedigrees: Studies of Schuppius in 1912 and Wittermann in 1913 Kraepelin对精神失智症和躁狂抑郁性精神错乱的诊断在家系中的检验：1912年对Schuppius和1913年对Wittermann的研究。

IF 2.8 3区医学

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Pub Date : 2023-06-08 DOI: 10.1002/ajmg.b.32950

Kenneth S. Kendler, Astrid Klee

{"title":"The examination of Kraepelin's diagnoses of dementia praecox and manic-depressive insanity in pedigrees: Studies of Schuppius in 1912 and Wittermann in 1913","authors":"Kenneth S. Kendler, Astrid Klee","doi":"10.1002/ajmg.b.32950","DOIUrl":"10.1002/ajmg.b.32950","url":null,"abstract":"In the first two decades of the 20th century, a new approach to psychiatric genetics research emerged in Germany from three roots: (i) the wide-spread acceptance of Kraepelin's diagnostic system, (ii) increasing interest in pedigree research, and (iii) excitement about Mendelian models. We review two relevant papers, reporting analyses of, respectively, 62 and 81 pedigrees: S. Schuppius in 1912 and E. Wittermann in 1913. While most prior asylum based studies only reported a patient's “hereditary burden,” they examined diagnoses of individual relatives at a particular place in a pedigree. Both authors focused on the segregation of dementia praecox (DP) and manic-depressive insanity (MDI). Schuppius reported that the two disorders frequently co-occurred in his pedigrees while Wittermann found them to be largely independent. Schuppius was skeptical of the feasibility of evaluating Mendelian models in humans. Wittermann, by contrast, with advice from Wilhelm Weinberg, applied algebraic models with proband correction to DP in his sibships with results consistent with autosomal recessive transmission. While he had less data, Wittermann suggested that MDI was likely an autosomal dominant disorder. Both authors were interested in other disorders or traits appearing in pedigrees dense with DP (e.g., idiocy) or MDI (e.g., highly excitable individuals).","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"192 7-8","pages":"113-123"},"PeriodicalIF":2.8,"publicationDate":"2023-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.b.32950","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9584130","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: 1

Genetic examination of the Mood Disorder Questionnaire and its relationship with bipolar disorder 情绪障碍问卷的基因检查及其与双相情感障碍的关系。

IF 2.8 3区医学

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Pub Date : 2023-05-13 DOI: 10.1002/ajmg.b.32938

Jessica Mundy, Christopher Hübel, Brett N. Adey, Helena L. Davies, Molly R. Davies, Jonathan R. I. Coleman, Matthew Hotopf, Gursharan Kalsi, Sang Hyuck Lee, Andrew M. McIntosh, Henry C. Rogers, Thalia C. Eley, Robin M. Murray, Evangelos Vassos, Gerome Breen

{"title":"Genetic examination of the Mood Disorder Questionnaire and its relationship with bipolar disorder","authors":"Jessica Mundy, Christopher Hübel, Brett N. Adey, Helena L. Davies, Molly R. Davies, Jonathan R. I. Coleman, Matthew Hotopf, Gursharan Kalsi, Sang Hyuck Lee, Andrew M. McIntosh, Henry C. Rogers, Thalia C. Eley, Robin M. Murray, Evangelos Vassos, Gerome Breen","doi":"10.1002/ajmg.b.32938","DOIUrl":"10.1002/ajmg.b.32938","url":null,"abstract":"The Mood Disorder Questionnaire (MDQ) is a common screening tool for bipolar disorder that assesses manic symptoms. Its utility for genetic studies of mania or bipolar traits has not been fully examined. We psychometrically compared the MDQ to self-reported bipolar disorder in participants from the United Kingdom National Institute of Health and Care Research Mental Health BioResource. We conducted genome-wide association studies of manic symptom quantitative traits and symptom subgroups, derived from the MDQ items (N = 11,568–19,859). We calculated genetic correlations with bipolar disorder and other psychiatric and behavioral traits. The MDQ screener showed low positive predictive value (0.29) for self-reported bipolar disorder. Neither concurrent nor lifetime manic symptoms were genetically correlated with bipolar disorder. Lifetime manic symptoms had a highest genetic correlation (rg = 1.0) with posttraumatic stress disorder although this was not confirmed by within-cohort phenotypic correlations (rp = 0.41). Other significant genetic correlations included attention deficit hyperactivity disorder (rg = 0.69), insomnia (rg = 0.55), and major depressive disorder (rg = 0.42). Our study adds to existing literature questioning the MDQ's validity and suggests it may capture symptoms of general distress or psychopathology, rather than hypomania/mania specifically, in at-risk populations.","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"192 7-8","pages":"147-160"},"PeriodicalIF":2.8,"publicationDate":"2023-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.b.32938","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9447115","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: 3

How do experts in psychiatric genetics view the clinical utility of polygenic risk scores for schizophrenia? 精神遗传学专家如何看待精神分裂症多基因风险评分的临床效用？

IF 2.8 3区医学

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Pub Date : 2023-05-09 DOI: 10.1002/ajmg.b.32939

Tiahna Moorthy, Huyen Nguyen, Ying Chen, Jehannine Austin, Jordan W. Smoller, Laura Hercher, Maya Sabatello

{"title":"How do experts in psychiatric genetics view the clinical utility of polygenic risk scores for schizophrenia?","authors":"Tiahna Moorthy, Huyen Nguyen, Ying Chen, Jehannine Austin, Jordan W. Smoller, Laura Hercher, Maya Sabatello","doi":"10.1002/ajmg.b.32939","DOIUrl":"10.1002/ajmg.b.32939","url":null,"abstract":"Polygenic risk scores (PRS) are promising for identifying common variant-related inheritance for psychiatric conditions but their integration into clinical practice depends on their clinical utility and psychiatrists' understanding of PRS. Our online survey explored these issues with 276 professionals working in psychiatric genetics (RR: 19%). Overall, participants demonstrated knowledge of how to interpret PRS results. Their performance on knowledge-based questions was positively correlated with participants' self-reported familiarity with PRS (r = 0.21, p = 0.0006) although differences were not statistically significant (Wald Chi-square = 3.29, df = 1, p = 0.07). However, only 48.9% of all participants answered all knowledge questions correctly. Many participants (56.5%), especially researchers (42%), indicated having at least occasional conversations about the role of genetics in psychiatric conditions with patients and/or family members. Most participants (62.7%) indicated that PRS are not yet sufficiently robust for assessment of susceptibility to schizophrenia; most significant obstacles were low predictive power and lack of population diversity in available PRS (selected, respectively, by 53.6% and 29.3% of participants). Nevertheless, 89.8% of participants were optimistic about the use of PRS in the next 10 years, suggesting a belief that current shortcomings could be addressed. Our findings inform about the perceptions of psychiatric professionals regarding PRS and the application of PRS in psychiatry.","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"192 7-8","pages":"161-170"},"PeriodicalIF":2.8,"publicationDate":"2023-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.b.32939","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9798904","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

Irma Weinberg's 1928 paper “on the problem of the determination of heredity prognosis: The risk in the cousins of schizophrenics” Irma Weinberg 1928年的论文“关于遗传预后的确定问题：精神分裂症患者近亲的风险”。

IF 2.8 3区医学

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Pub Date : 2023-04-17 DOI: 10.1002/ajmg.b.32937

Kenneth S. Kendler, Astrid Klee, Eric J. Engstrom

{"title":"Irma Weinberg's 1928 paper “on the problem of the determination of heredity prognosis: The risk in the cousins of schizophrenics”","authors":"Kenneth S. Kendler, Astrid Klee, Eric J. Engstrom","doi":"10.1002/ajmg.b.32937","DOIUrl":"10.1002/ajmg.b.32937","url":null,"abstract":"Irma Weinberg, a German-Jewish Neuropsychiatrist/Physician, authored the fourth report from the German Research Institute for Psychiatry in Munich examining the risk for dementia praecox (DP) in particular relatives of DP probands, here first-cousins. She examined 977 cousins of 54 DP probands and found a best-estimate risk of 1.4%. She conducted within-study analyses, showing a much higher risk for DP in the siblings than cousins of DP probands. She studied DP-related personalities showing a familial link between these conditions and risk for DP. She demonstrated that the risk for DP in cousins was impacted substantially by the distribution, in ancestors, of psychosis and personality abnormalities. After completing work on this article, Weinberg worked in private practice in Frankfurt, emigrating to the Netherlands in 1934, where she worked at a Jewish psychiatric hospital. In 1943, German occupiers evacuated the hospital, transporting the patients and staff, either directly to Auschwitz or, like Weinberg, to the Westerbork transit camp. On September 4, 1944, Dr. Weinberg was transported to Theresienstadt and soon thereafter to Auschwitz, where she was murdered at the age of 53. Her history raises painful questions about the relationship between genetic studies of psychiatric illness in prewar Germany and the Holocaust.","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"192 7-8","pages":"105-112"},"PeriodicalIF":2.8,"publicationDate":"2023-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.b.32937","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9665495","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

Issue Information ‐ TOC 问题信息-TOC

IF 2.8 3区医学

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Pub Date : 2023-04-01 DOI: 10.1111/1467-923x.13142

引用次数: 0

Polygenic prediction of bipolar disorder in a Latin American sample 拉丁美洲样本中双相情感障碍的多基因预测。

IF 2.8 3区医学

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Pub Date : 2023-03-15 DOI: 10.1002/ajmg.b.32936

Alfredo B. Cuellar-Barboza, Miguel L. Prieto, Brandon J. Coombes, Manuel Gardea-Resendez, Nicolás Núñez, Stacey J. Winham, Francisco Romo-Nava, Sarai González, Susan L. McElroy, Mark A. Frye, Joanna M. Biernacka

{"title":"Polygenic prediction of bipolar disorder in a Latin American sample","authors":"Alfredo B. Cuellar-Barboza, Miguel L. Prieto, Brandon J. Coombes, Manuel Gardea-Resendez, Nicolás Núñez, Stacey J. Winham, Francisco Romo-Nava, Sarai González, Susan L. McElroy, Mark A. Frye, Joanna M. Biernacka","doi":"10.1002/ajmg.b.32936","DOIUrl":"10.1002/ajmg.b.32936","url":null,"abstract":"To date, bipolar disorder (BD) genetic studies and polygenic risk scores (PRSs) for BD are based primarily on populations of European descent (EUR) and lack representation from other ancestries including Latin American (LAT). Here, we describe a new LAT cohort from the Mayo Clinic Bipolar Biobank (MCBB), a multisite collaboration with recruitment sites in the United States (EUR; 1,443 cases and 777 controls) and Mexico and Chile (LAT; 211 cases and 161 controls) and use the sample to explore the performance of a BD-PRS in a LAT population. Using results from the largest genome-wide association study of BD in EUR individuals, PRSice2 and LDpred2 were used to compute BD-PRSs in the LAT and EUR samples from the MCBB. PRSs explained up to 1.4% (PRSice) and 4% (LDpred2) of the phenotypic variance on the liability scale in the LAT sample compared to 3.8% (PRSice2) and 3.4% (LDpred2) in the EUR samples. Future larger studies should further explore the differential performance of different PRS approaches across ancestries. International multisite studies, such as this one, have the potential to address diversity-related limitations of prior genomic studies and ultimately contribute to the reduction of health disparities.","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"192 7-8","pages":"139-146"},"PeriodicalIF":2.8,"publicationDate":"2023-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9113242","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

De novo mutations disturb early brain development more frequently than common variants in schizophrenia 新生突变比精神分裂症的常见变异更频繁地干扰早期大脑发育

IF 2.8 3区医学

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Pub Date : 2023-03-02 DOI: 10.1002/ajmg.b.32932

Toshiyuki Itai, Peilin Jia, Yulin Dai, Jingchun Chen, Xiangning Chen, Zhongming Zhao

{"title":"De novo mutations disturb early brain development more frequently than common variants in schizophrenia","authors":"Toshiyuki Itai, Peilin Jia, Yulin Dai, Jingchun Chen, Xiangning Chen, Zhongming Zhao","doi":"10.1002/ajmg.b.32932","DOIUrl":"10.1002/ajmg.b.32932","url":null,"abstract":"Investigating functional, temporal, and cell-type expression features of mutations is important for understanding a complex disease. Here, we collected and analyzed common variants and de novo mutations (DNMs) in schizophrenia (SCZ). We collected 2,636 missense and loss-of-function (LoF) DNMs in 2,263 genes across 3,477 SCZ patients (SCZ-DNMs). We curated three gene lists: (a) SCZ-neuroGenes (159 genes), which are intolerant to LoF and missense DNMs and are neurologically important, (b) SCZ-moduleGenes (52 genes), which were derived from network analyses of SCZ-DNMs, and (c) SCZ-commonGenes (120 genes) from a recent GWAS as reference. To compare temporal gene expression, we used the BrainSpan dataset. We defined a fetal effect score (FES) to quantify the involvement of each gene in prenatal brain development. We further employed the specificity indexes (SIs) to evaluate cell-type expression specificity from single-cell expression data in cerebral cortices of humans and mice. Compared with SCZ-commonGenes, SCZ-neuroGenes and SCZ-moduleGenes were highly expressed in the prenatal stage, had higher FESs, and had higher SIs in fetal replicating cells and undifferentiated cell types. Our results suggested that gene expression patterns in specific cell types in early fetal stages might have impacts on the risk of SCZ during adulthood.","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"192 3-4","pages":"62-70"},"PeriodicalIF":2.8,"publicationDate":"2023-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9398672","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 impact of receiving polygenic risk scores for alcohol use disorder on psychological distress, risk perception, and intentions to reduce drinking 接受酒精使用障碍多基因风险评分对心理困扰、风险感知和减少饮酒意愿的影响

IF 2.8 3区医学

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Pub Date : 2023-03-01 DOI: 10.1002/ajmg.b.32933

Morgan N. Driver, Sally I-Chun Kuo, Jacqueline S. Dron, Jehannine Austin, Danielle M. Dick

{"title":"The impact of receiving polygenic risk scores for alcohol use disorder on psychological distress, risk perception, and intentions to reduce drinking","authors":"Morgan N. Driver, Sally I-Chun Kuo, Jacqueline S. Dron, Jehannine Austin, Danielle M. Dick","doi":"10.1002/ajmg.b.32933","DOIUrl":"10.1002/ajmg.b.32933","url":null,"abstract":"For the return of polygenic risk scores to become an acceptable clinical practice in psychiatry, receipt of polygenic risk scores must be associated with minimal harm and changes in behavior that decrease one's risk for developing a psychiatric outcome. Data from a randomized controlled trial was used to assess the impact of different levels of hypothetical polygenic risk scores for alcohol use disorder on psychological distress, risk perception, and intentions to change drinking behaviors. The analytic sample consisted of 325 participants recruited from an urban, public university. Results demonstrated that there were significant increases in psychological distress as the level of genetic risk for alcohol use disorder increased. In addition, the perceived chance of developing alcohol use disorder significantly increased as the level of genetic risk increased. Promisingly, a greater proportion of participants indicated that they would intend to engage in follow-up behaviors, such as seeking additional information, talking to a healthcare provider about risk, and reducing drinking behaviors, as the level of genetic risk increased. Returning polygenic risk scores for alcohol use disorder in a clinical setting has the potential to promote risk-reducing behavior change, especially with increasing levels of genetic risk. The study was registered on ClinicalTrials.gov (Identifier: NCT05143073).","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"192 5-6","pages":"93-101"},"PeriodicalIF":2.8,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.b.32933","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9869816","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

The era of the Dawn of Mendelian research in the field of psychiatry: Rüdin's 1922 review paper “regarding the heredity of mental disturbances” 精神病学领域孟德尔式研究的黎明时代:r<e:1>丁1922年的评论论文“关于精神障碍的遗传”

IF 2.8 3区医学

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Pub Date : 2023-02-27 DOI: 10.1002/ajmg.b.32934

Kenneth S. Kendler, Astrid Klee

{"title":"The era of the Dawn of Mendelian research in the field of psychiatry: Rüdin's 1922 review paper “regarding the heredity of mental disturbances”","authors":"Kenneth S. Kendler, Astrid Klee","doi":"10.1002/ajmg.b.32934","DOIUrl":"10.1002/ajmg.b.32934","url":null,"abstract":"On September 27, 1922, Ernst Rüdin gave an address to the Annual Conference of the German Society of Genetics entitled “Regarding the Heredity of Mental Disturbances.” Published in a 37-page article, Rüdin reviewed the progress in the field of Mendelian psychiatric genetics, then hardly more than a decade old. Topics included (a) the status of Mendelian analyses of dementia praecox and manic-depressive insanity which had expanded to include two and three locus and early polygenic models and sometimes included, respectively, schizoid and cyclothymic personalities; (b) a critique of theories for the explanation of co-occurrence of different psychiatric disorders within families; and (c) a sharp methodologic critique of Davenport and Rosanoff's contemporary work which emphasized Rüdin's commitment to careful, expert phenotyping, a primary focus on well-validated psychiatric disorders and not broad spectra of putatively inter-related conditions, and an emphasis on rigorous statistical modeling as seen in his continued collaboration with Wilhelm Weinberg.","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"192 3-4","pages":"53-61"},"PeriodicalIF":2.8,"publicationDate":"2023-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.b.32934","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9335411","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

The relationship between case–control differential gene expression from brain tissue and genetic associations in schizophrenia 精神分裂症病例-对照脑组织差异基因表达与遗传关联的关系

IF 2.8 3区医学

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Pub Date : 2023-01-18 DOI: 10.1002/ajmg.b.32931

Nicholas E. Clifton, Anton Schulmann, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Peter A. Holmans, Michael C. O'Donovan, Marquis P. Vawter

{"title":"The relationship between case–control differential gene expression from brain tissue and genetic associations in schizophrenia","authors":"Nicholas E. Clifton, Anton Schulmann, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Peter A. Holmans, Michael C. O'Donovan, Marquis P. Vawter","doi":"10.1002/ajmg.b.32931","DOIUrl":"10.1002/ajmg.b.32931","url":null,"abstract":"Large numbers of genetic loci have been identified that are known to contain common risk alleles for schizophrenia, but linking associated alleles to specific risk genes remains challenging. Given that most alleles that influence liability to schizophrenia are thought to do so by altered gene expression, intuitively, case–control differential gene expression studies should highlight genes with a higher probability of being associated with schizophrenia and could help identify the most likely causal genes within associated loci. Here, we test this hypothesis by comparing transcriptome analysis of the dorsolateral prefrontal cortex from 563 schizophrenia cases and 802 controls with genome-wide association study (GWAS) data from the third wave study of the Psychiatric Genomics Consortium. Genes differentially expressed in schizophrenia were not enriched for common allelic association statistics compared with other brain-expressed genes, nor were they enriched for genes within associated loci previously reported to be prioritized by genetic fine-mapping. Genes prioritized by Summary-based Mendelian Randomization were underexpressed in cases compared to other genes in the same GWAS loci. However, the overall strength and direction of expression change predicted by SMR were not related to that observed in the differential expression data. Overall, this study does not support the hypothesis that genes identified as differentially expressed from RNA sequencing of bulk brain tissue are enriched for those that show evidence for genetic associations. Such data have limited utility for prioritizing genes in currently associated loci in schizophrenia.","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"192 5-6","pages":"85-92"},"PeriodicalIF":2.8,"publicationDate":"2023-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.b.32931","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10225357","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