American Journal of Medical Genetics Part B: Neuropsychiatric Genetics最新文献

{"title":"Integrative multi-omics analysis of genomic, epigenomic, and metabolomics data leads to new insights for Attention-Deficit/Hyperactivity Disorder","authors":"Nikki Hubers, F. Hagenbeek, R. Pool, S. Déjean, A. Harms, Peter J. Roetman, C. V. van Beijsterveldt, V. Fanos, E. Ehli, R. Vermeiren, M. Bartels, J. Hottenga, T. Hankemeier, J. van Dongen, D. Boomsma","doi":"10.1101/2022.07.21.22277887","DOIUrl":"https://doi.org/10.1101/2022.07.21.22277887","url":null,"abstract":"The evolving field of multi-omics combines data across omics levels and provides methods for simultaneous analysis. We integrated genomics (transmitted and non-transmitted polygenic scores), epigenomics and metabolomics data in a multi-omics framework to identify biomarkers for ADHD and investigated the connections among omics levels. We trained single- and multi-omics models to differentiate between cases and controls in 596 twins (cases=14.8%) from the Netherlands Twin Register (NTR) demonstrating reasonable in-sample prediction through cross-validation. Out-of-sample prediction in NTR participants (N=258, cases=14.3%) and in a clinical sample (N=145, cases=51%) did not perform well (range misclassification: 0.40-0.57). The multi-omics model selected 30 PGSs, 143 CpGs, and 90 metabolites. We confirmed previous associations with ADHD such as with glucocorticoid exposure and the transmembrane protein family TMEM, show that the DNA methylation of the MAD1L1 gene associated with ADHD has a relation with parental smoking behavior and present novel findings including associations between indirect genetic effects and CpGs of the STAP2 gene. The results highlighted connections between omics levels, with the strongest connections between indirect genetic effects, CpGs, and amino acid levels. Our study shows that multi-omics designs considering interrelated omics levels can help unravel the complex biology underlying ADHD.","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"82 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2022-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89847504","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}

{"title":"A phenome-wide association study of polygenic scores for attention deficit hyperactivity disorder across two genetic ancestries in electronic health record data","authors":"Maria Niarchou,&nbsp;Julia M. Sealock,&nbsp;Peter Straub,&nbsp;Sandra Sanchez-Roige,&nbsp;James S. Sutcliffe,&nbsp;Lea K. Davis","doi":"10.1002/ajmg.b.32911","DOIUrl":"10.1002/ajmg.b.32911","url":null,"abstract":"<p>Testing the association between genetic scores for Attention Deficit Hyperactivity Disorder (ADHD) and health conditions, can help us better understand its complex etiology. Electronic health records linked to genetic data provide an opportunity to test whether genetic scores for ADHD correlate with ADHD and additional health outcomes in a health care context across different age groups. We generated polygenic scores (ADHD-PGS) trained on summary statistics from the latest genome-wide association study of ADHD (<i>N</i> = 55,374) and applied them to genome-wide data from 12,383 unrelated individuals of African-American ancestry and 66,378 unrelated individuals of European ancestry from the Vanderbilt Biobank. Overall, only Tobacco use disorder (TUD) was associated with ADHD-PGS in the African-American ancestry group (Odds ratio [95% confidence intervals] = 1.23[1.16–1.31], <i>p</i> = 9.3 × 10⁻⁰⁹). Eighty-six phenotypes were associated with ADHD-PGS in the European ancestry individuals, including ADHD (OR[95%CIs] = 1.22[1.16–1.29], <i>p</i> = 3.6 × 10⁻¹⁰), and TUD (OR[95%CIs] = 1.22[1.19–1.25], <i>p</i> = 2.8 × 10⁻⁴⁶). We then stratified outcomes by age (ages 0–11, 12–18, 19–25, 26–40, 41–60, and 61–100). Our results suggest that ADHD polygenic scores are associated with ADHD diagnoses early in life and with an increasing number of health conditions throughout the lifespan (even in the absence of ADHD diagnosis). This study reinforces the utility of applying trait-specific PGSs to biobank data, and performing exploratory sensitivity analyses, to probe relationships among clinical conditions.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"189 6","pages":"185-195"},"PeriodicalIF":2.8,"publicationDate":"2022-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c8/21/AJMG-189-185.PMC9378640.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10686000","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}

{"title":"The shared genetic basis of mood instability and psychiatric disorders: A cross-trait genome-wide association analysis","authors":"Guy Hindley,&nbsp;Kevin S. O'Connell,&nbsp;Zillur Rahman,&nbsp;Oleksandr Frei,&nbsp;Shahram Bahrami,&nbsp;Alexey Shadrin,&nbsp;Margrethe C. Høegh,&nbsp;Weiqiu Cheng,&nbsp;Naz Karadag,&nbsp;Aihua Lin,&nbsp;Linn Rødevand,&nbsp;Chun C. Fan,&nbsp;Srdjan Djurovic,&nbsp;Trine V. Lagerberg,&nbsp;Anders M. Dale,&nbsp;Olav B. Smeland,&nbsp;Ole A. Andreassen","doi":"10.1002/ajmg.b.32907","DOIUrl":"10.1002/ajmg.b.32907","url":null,"abstract":"<p>Recent genome-wide association studies of mood instability (MOOD) have found significant positive genetic correlation with major depression (DEP) and weak correlations with other psychiatric disorders. We investigated the polygenic overlap between MOOD and psychiatric disorders beyond genetic correlation to better characterize putative shared genetic determinants. GWAS summary statistics for schizophrenia (SCZ, <i>n</i> = 105,318), bipolar disorder (BIP, <i>n</i> = 413,466), DEP (<i>n</i> = 450,619), attention-deficit hyperactivity disorder (ADHD, <i>n</i> = 53,293), and MOOD (<i>n</i> = 363,705) were analyzed using the bivariate causal mixture model and conjunctional false discovery rate methods. MOOD correlated positively with all psychiatric disorders, but with wide variation in strength (<i>r</i>_g = 0.10–0.62). Of 10.4 K genomic variants influencing MOOD, 4 K–9.4 K influenced psychiatric disorders. Furthermore, MOOD was jointly associated with DEP at 163 loci, SCZ at 110, BIP at 60 and ADHD at 25. Fifty-three jointly associated loci were overlapping across two or more disorders, seven of which had discordant effect directions on psychiatric disorders. Genes mapped to loci associated with MOOD and all four disorders were enriched in a single gene-set, “synapse organization.” The extensive polygenic overlap indicates shared molecular underpinnings across MOOD and psychiatric disorders. However, distinct patterns of genetic correlation and effect directions may relate to differences in the core clinical features of each disorder.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"189 6","pages":"207-218"},"PeriodicalIF":2.8,"publicationDate":"2022-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9541703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10841886","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}

{"title":"Clinical, demographic, and genetic risk factors of treatment-attributed suicidality in >10,000 Australian adults taking antidepressants","authors":"Adrian I. Campos,&nbsp;Enda M. Byrne,&nbsp;Frank Iorfino,&nbsp;Chiara Fabbri,&nbsp;Ian B. Hickie,&nbsp;Cathryn M. Lewis,&nbsp;Naomi R. Wray,&nbsp;Sarah E. Medland,&nbsp;Miguel E. Rentería,&nbsp;Nicholas G. Martin","doi":"10.1002/ajmg.b.32913","DOIUrl":"10.1002/ajmg.b.32913","url":null,"abstract":"<p>Emergence of suicidal symptoms has been reported as a potential antidepressant adverse drug reaction. Identifying risk factors associated could increase our understanding of this phenomenon and stratify individuals at higher risk. Logistic regressions were used to identify risk factors of self-reported treatment-attributed suicidal ideation (TASI). We then employed classifiers to test the predictive ability of the variables identified. A TASI GWAS, as well as SNP-based heritability estimation, were performed. GWAS replication was sought from an independent study. Significant associations were found for age and comorbid conditions, including bipolar and personality disorders. Participants reporting TASI from one antidepressant were more likely to report TASI from other antidepressants. No genetic loci associated with TAS I (<i>p</i> &lt; 5e-8) were identified. Of 32 independent variants with suggestive association (<i>p</i> &lt; 1e-5), 27 lead SNPs were available in a replication dataset from the GENDEP study. Only one variant showed a consistent effect and nominal association in the independent replication sample. Classifiers were able to stratify non-TASI from TASI participants (AUC = 0.77) and those reporting treatment-attributed suicide attempts (AUC = 0.85). The pattern of TASI co-occurrence across participants suggest nonspecific factors underlying its etiology. These findings provide insights into the underpinnings of TASI and serve as a proof-of-concept of the use of classifiers for risk stratification.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"189 6","pages":"196-206"},"PeriodicalIF":2.8,"publicationDate":"2022-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9544797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40615322","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}

{"title":"FOXO4 alleviates hippocampal neuronal damage in epileptic mice via the miR-138-5p/ROCK2 axis","authors":"Xin Jin,&nbsp;Xingjuan Liao,&nbsp;Longfei Wu,&nbsp;Jianling Huang,&nbsp;Zhimin Li,&nbsp;Yali Li,&nbsp;Fan Guo","doi":"10.1002/ajmg.b.32904","DOIUrl":"10.1002/ajmg.b.32904","url":null,"abstract":"<p>Epilepsy (EP) is one of the most universal neurological disorders. This study investigated the mechanism of forkhead box protein O4 (FOXO4) on hippocampal neuronal damage in EP mice. Initially, the EP mouse model and the in vitro HT-22 cell model were established. EP seizures and neuronal damage in mice were assessed. FOXO4, microRNA (miR)-138-5p, and rho-associated coiled-coil containing protein kinase 2 (ROCK2) levels in hippocampal tissues or HT-22 cells were examined. The cell viability and apoptosis of HT-22 cells were determined. The concentrations of oxidative stress markers and the levels of inflammatory cytokines in hippocampal tissues or HT-22 cells were detected. We found that FOXO4 was poorly expressed in EP. FOXO4 overexpression alleviated hippocampal neuronal damage in EP mice and improved HT-22 cell viability and inhibited apoptosis, and decreased oxidative stress and inflammation in hippocampal tissue and HT-22 cells. The bindings of miR-138-5p to FOXO4 and ROCK2 were analyzed, which showed that FOXO4 promoted miR-138-5p via binding to the miR-138-5p promoter region, and miR-138-5p inhibited ROCK2 expression. Joint experiments showed that miR-138-5p suppression or ROCK2 overexpression reversed the alleviation of FOXO4 overexpression on hippocampal neuronal damage. FOXO4 inhibited ROCK2 expression via promoting miR-138-5p expression, thus alleviating hippocampal neuronal damage in EP mice.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"189 7-8","pages":"271-284"},"PeriodicalIF":2.8,"publicationDate":"2022-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10636042","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}

{"title":"Psychiatric polygenic risk scores: Child and adolescent psychiatrists' knowledge, attitudes, and experiences","authors":"Stacey Pereira,&nbsp;Katrina A. Muñoz,&nbsp;Brent J. Small,&nbsp;Takahiro Soda,&nbsp;Laura N. Torgerson,&nbsp;Clarissa E. Sanchez,&nbsp;Jehannine Austin,&nbsp;Eric A. Storch,&nbsp;Gabriel Lázaro-Muñoz","doi":"10.1002/ajmg.b.32912","DOIUrl":"10.1002/ajmg.b.32912","url":null,"abstract":"<p>Psychiatric polygenic risk scores (PRS) have potential utility in psychiatric care and prevention, but there are concerns about their implementation. We surveyed 960 US-based practicing child and adolescent psychiatrists' (CAP) about their experiences, perspectives, and potential uses of psychiatric PRS. While 23% of CAP reported that they had never heard of PRS, 10 % of respondents have had a patient/family bring PRS to them and 4% have generated PRS for patients. Though 25% stated they would request PRS if a patient/caregiver asked, 35% indicated that nothing would prompt them to request PRS. Most respondents (54%) believed psychiatric PRS are currently at least slightly useful and 87% believed they will be so in 5 years. More than 70% indicated they would take action in response to a child with a top fifth percentile psychiatric PRS but no diagnosis: 48% would increase monitoring of symptoms, 42% would evaluate for current symptoms, and 4% would prescribe medications. Yet, most respondents were concerned that high-PRS results could lead to overtreatment and negatively impact patients' emotional well-being. Findings indicate emerging use of psychiatric PRS within child and adolescent psychiatry in the US. It is critical to examine the ethical and clinical challenges that PRS may generate and begin efforts to promote their informed and responsible use.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"189 7-8","pages":"293-302"},"PeriodicalIF":2.8,"publicationDate":"2022-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10689807","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}

{"title":"Recommendations to encourage participation of individuals from diverse backgrounds in psychiatric genetic studies","authors":"Casey MacDermod,&nbsp;Michaela A. Pettie,&nbsp;Emily A. Carrino,&nbsp;Susana Cruz Garcia,&nbsp;Sophie Padalecki,&nbsp;Jody E. Finch,&nbsp;Christina Sanzari,&nbsp;Hannah L. Kennedy,&nbsp;Pratiksha S. Pawar,&nbsp;Makenna M. Mcgough,&nbsp;Ava Iwashita,&nbsp;Mary Takgbajouah,&nbsp;Danielle Coan,&nbsp;Lindsey Szakasits,&nbsp;Rachel W. Goode,&nbsp;Ya-Ke Wu,&nbsp;Mae Lynn Reyes-Rodríguez,&nbsp;Eva María Trujillo Chi Vacuán,&nbsp;Martin A. Kennedy,&nbsp;Lana Cleland,&nbsp;Jennifer Jordan,&nbsp;Sarah Maguire,&nbsp;Jerry D. Guintivano,&nbsp;Paola Giusti-Rodríguez,&nbsp;Jessica H. Baker,&nbsp;Laura M. Thornton,&nbsp;Cynthia M. Bulik","doi":"10.1002/ajmg.b.32906","DOIUrl":"10.1002/ajmg.b.32906","url":null,"abstract":"<p>We present innovative research practices in psychiatric genetic studies to ensure representation of individuals from diverse ancestry, sex assigned at birth, gender identity, age, body shape and size, and socioeconomic backgrounds. Due to histories of inappropriate and harmful practices against marginalized groups in both psychiatry and genetics, people of certain identities may be hesitant to participate in research studies. Yet their participation is essential to ensure diverse representation, as it is incorrect to assume that the same genetic and environmental factors influence the risk for various psychiatric disorders across all demographic groups. We present approaches developed as part of the Eating Disorders Genetics Initiative (EDGI), a study that required tailored approaches to recruit diverse populations across many countries. Considerations include research priorities and design, recruitment and study branding, transparency, and community investment and ownership. Ensuring representation in participants is costly and funders need to provide adequate support to achieve diversity in recruitment in prime awards, not just as supplemental afterthoughts. The need for diverse samples in genetic studies is critical to minimize the risk of perpetuating health disparities in psychiatry and other health research. Although the EDGI strategies were designed specifically to attract and enroll individuals with eating disorders, our approach is broadly applicable across psychiatry and other fields.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"189 5","pages":"163-173"},"PeriodicalIF":2.8,"publicationDate":"2022-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a4/87/AJMG-189-163.PMC9542122.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9453554","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}

{"title":"The actions and interactions of family genetic risk scores for alcohol use disorder and major depression on the risk for these two disorders","authors":"Kenneth S. Kendler,&nbsp;Sara L. Lönn,&nbsp;Jan Sundquist,&nbsp;Kristina Sundquist","doi":"10.1002/ajmg.b.32909","DOIUrl":"10.1002/ajmg.b.32909","url":null,"abstract":"<p>We know little about how genetic risk factors for two disorders jointly act and interact in predisposing to illness. Therefore, in the Swedish population, born 1970–1990 (<i>n</i> = 2,116,082) and followed through 2015, we examine, using additive Cox models, the impact of the family genetic risk scores (FGRS) for alcohol use disorder (AUD) and major depression (MD), their interaction with each other and with the relevant comorbid disorder on risk for AUD and MD. FGRS scores are constructed using rates of illness in first-fourth degree relatives. FGRS for AUD and MD interacted in predicting of both disorders and one FRGS (e.g., for AUD) interacted with the phenotype of MD to predict that disorder (e.g., AUD). These FGRS interactions were not substantially attenuated by adding interactions with the disorders. These results replicated across sexes. In predicting risk for a given disorder, we rarely consider genetic liabilities for other disorders. But such effects were here significant and interactive. Furthermore, the primary disorder genetic risk interacts with comorbid disorders. The pathways to risk for disorders from their and other disorders' genetic liability may be more complex than commonly considered.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"189 5","pages":"128-138"},"PeriodicalIF":2.8,"publicationDate":"2022-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9469448","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}

{"title":"Medical genetics in the 19th century as background to the development of psychiatric genetics","authors":"Kenneth S. Kendler","doi":"10.1002/ajmg.b.32910","DOIUrl":"10.1002/ajmg.b.32910","url":null,"abstract":"<p>This article examines the relationship between the early efforts of alienists to understand the role of heredity in the etiology of insanity in the 19th century and the parallel efforts of the nascent discipline of medical genetics. I review three monographs on general medical genetics: Adams in 1814, Steinau in 1843, and Lithgow in 1889. Numerous parallels were seen between their writings and those of their contemporary alienists working on mental disorders including (i) an emphasis on the transmission of the liability to illness rather than the illness itself, (ii) discussions of the homogeneous versus heterogeneous nature of familial transmission of disease, (iii) the relative value of direct versus indirect hereditary effects, (iv) the role of mothers versus fathers in transmitting liability, (v) possible environmental sources of familial clustering, and (vi) the transmission of age at onset of illness. All three medical genetic authors noted that insanity was among the more heritable of human disorders. Furthermore, Lithgow noted the importance of heritable influences on the non-psychotic forms of psychiatric illness rarely seen in asylums. This survey demonstrates substantial consilience in the topics of interest and conclusions of the nascent general medical and psychiatric genetics' communities in the 19th century.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"189 5","pages":"119-127"},"PeriodicalIF":2.8,"publicationDate":"2022-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40464503","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}

{"title":"Cover Image, Volume 189B, Number 5, July 2022","authors":"","doi":"10.1002/ajmg.b.32854","DOIUrl":"https://doi.org/10.1002/ajmg.b.32854","url":null,"abstract":"","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"1 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44228269","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}