Twin Research and Human Genetics最新文献

{"title":"DNA Methylation Mediated the Association of Body Mass Index With Blood Pressure in Chinese Monozygotic Twins.","authors":"Jie Yao, Feng Ning, Weijing Wang, Dongfeng Zhang","doi":"10.1017/thg.2024.3","DOIUrl":"10.1017/thg.2024.3","url":null,"abstract":"<p><p>Obesity is an established risk factor for hypertension, but the mechanisms are only partially understood. We examined whether body mass index (BMI)-related DNA methylation (DNAm) variation would mediate the association of BMI with blood pressure (BP). We first conducted a genomewide DNA methylation analysis in monozygotic twin pairs to detect BMI-related DNAm variation and then evaluated the mediating effect of DNAm on the relationship between BMI and BP levels using the causal inference test (CIT) method and mediation analysis. Ontology enrichment analysis was performed for CpGs using the GREAT tool. A total of 60 twin pairs for BMI and systolic blood pressure (SBP) and 58 twin pairs for BMI and diastolic blood pressure (DBP) were included. BMI was positively associated with SBP (β = 1.86, <i>p</i> = .0004). The association between BMI and DNAm of 85 CpGs reached <i>p</i> < 1×10^-4 level. Eleven BMI-related differentially methylated regions (DMRs) within <i>LNCPRESS1</i>, <i>OGDHL</i>, <i>RNU1-44P</i>, <i>NPHS1</i>, <i>ECEL1P2</i>, <i>LLGL2</i>, <i>RNY4P15</i>, <i>MOGAT3</i>, <i>PHACTR3</i>, and <i>BAI2</i> were found. Of the 85 CpGs, 9 mapped to <i>C10orf71-AS1</i>, <i>NDUFB5P1</i>, <i>KRT80</i>, <i>BAI2</i>, <i>ABCA2</i>, <i>PEX11G</i> and <i>FGF4</i> were significantly associated with SBP levels. Of the 9 CpGs, 2 within <i>ABCA2</i> negatively mediated the association between BMI and SBP, with a mediating effect of -0.24 (95% CI [-0.65, -0.01]). BMI was also positively associated with DBP (β = 0.60, <i>p</i> = .0495). The association between BMI and DNAm of 193 CpGs reached <i>p</i> < 1×10^-4 level. Twenty-five BMI-related DMRs within <i>OGDHL</i>, <i>POU4F2</i>, <i>ECEL1P2</i>, <i>TTC6</i>, <i>SMPD4</i>, <i>EP400</i>, <i>TUBA1C</i> and <i>AGAP2</i> were found. Of the 193 CpGs, 33 mapped to <i>ABCA2</i>, <i>ADORA2B</i>, <i>CTNNBIP1</i>, <i>KDM4B</i>, <i>NAA60</i>, <i>RSPH6A</i>, <i>SLC25A19</i> and <i>STIL</i> were significantly associated with DBP levels. Of the 33 CpGs, 12 within <i>ABCA2</i>, <i>SLC25A19</i>, <i>KDM4B</i>, <i>PTPRN2</i>, <i>DNASE1</i>, <i>TFCP2L1</i>, <i>LMNB2</i> and <i>C10orf71-AS1</i> negatively mediated the association between BMI and DBP, with a total mediation effect of -0.66 (95% CI [-1.07, -0.30]). Interestingly, BMI might also negatively mediate the association between the DNAm of most CpG mediators mentioned above and BP. The mediating effect of DNAm was also found when stratified by sex. In conclusion, DNAm variation may partially negatively mediate the association of BMI with BP. Our findings may provide new clues to further elucidate the pathogenesis of obesity to hypertension and identify new diagnostic biomarkers and therapeutic targets for hypertension.</p>","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":" ","pages":"18-29"},"PeriodicalIF":1.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139643008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Family History of Twinning and Fertility Traits in Nigerian Mothers of Dizygotic Twins.","authors":"Yoon-Mi Hur, Nick Martin, Olakunle Oginni, Dorret Boomsma, Nikki Hubers, Hamdi Mbarek","doi":"10.1017/thg.2024.2","DOIUrl":"10.1017/thg.2024.2","url":null,"abstract":"<p><p>Familial twinning and fertility traits were investigated in Nigerian mothers of dizygotic (DZ) twins (MoDZT; <i>N</i> = 972) and controls (<i>N</i> = 525) who responded to our person-to-person interview, which included questions on pregnancy history and family history of DZ twinning. Controls were defined as women who are not twins themselves and do not have twins in their first-degree relatives. Over 95% of the participants were Yoruba. We found that Nigerian MoDZT had an average of 4.0 (±2.6) pairs of twins among their relatives, and of these, the prevalence of DZ twins was significantly higher than that of monozygotic (MZ) twins (45.9% vs. 25.8%). Controls had an average of 0.5 (±0.4) pairs, and over 95% of the controls had no twins in their relatives. These results suggest genetic influences on DZ twinning in Nigerians. MoDZT were significantly younger in their mean age at first child, and had higher parity than controls, suggesting increased fertility in MoDZT. As compared to mothers with a single set of twins, mothers (<i>N</i> = 130) with multiple sets had significantly more twins among their relatives (5.4 pairs vs. 3.7 pairs) and had their first twins at a younger age (28.4 vs. 30.7 years), indicating that mothers with multiple sets of twins might have higher genetic propensity for twinning associated with earlier age at twin pregnancy. Our findings argue for genomewide association studies for DZ twinning in Nigerians, and may help to develop intervention strategies to overcome infertility/subfertility problems.</p>","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":" ","pages":"12-17"},"PeriodicalIF":1.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139643009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive Multiomics Analysis of Monozygotic Twin Discordant for Double Outlet Right Ventricle","authors":"Zhen Liu, Nana Li, Xiaoyu Pan, Jun Li, Shengli Li, Qintong Li, Ping Li, Ying Deng, Fang Chen, Hui Jiang, Wei Wang, Dezhi Mu, Ping Yu, Jun Zhu","doi":"10.1017/thg.2023.51","DOIUrl":"https://doi.org/10.1017/thg.2023.51","url":null,"abstract":"The objective of this study was to understand and measure epigenetic changes associated with the occurrence of CHDs by utilizing the discordant monozygotic twin model. A unique set of monozygotic twins discordant for double-outlet right ventricles (DORVs) was used for this multiomics study. The cardiac and muscle tissue samples from the twins were subjected to whole genome sequencing, whole genome bisulfite sequencing, RNA-sequencing and liquid chromatography-tandem mass spectrometry analysis. Sporadic DORV cases and control fetuses were used for validation. Global hypomethylation status was observed in heart tissue samples from the affected twins. Among 36,228 differentially methylated regions (DMRs), 1097 DMRs involving 1039 genes were located in promoter regions. A total of 419 genes, and lncRNA–mRNA pairs involved 30 genes, and 62 proteins were significantly differentially expressed. Multiple omics integrative analysis revealed that five genes, including <jats:italic>BGN</jats:italic>, <jats:italic>COL1A1</jats:italic>, <jats:italic>COL3A1</jats:italic>, <jats:italic>FBLN5</jats:italic>, and <jats:italic>FLAN</jats:italic>, and three pathways, including ECM-receptor interaction, focal adhesion and TGF-β signaling pathway, exhibited differences at all three levels. This study demonstrates a multiomics profile of discordant twins and explores the possible mechanism of DORV development. Global hypomethylation might be associated with the risk of CHDs. Specific genes and specific pathways, particularly those involving ECM–receptor interaction, focal adhesion and TGF–β signaling, might be involved in the occurrence of CHDs.","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":"98 1","pages":""},"PeriodicalIF":0.9,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138687535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"National Trends in Suicides and Male Twin Live Births in the US, 2003 to 2019: An Updated Test of Collective Optimism and Selection in Utero","authors":"Parvati Singh, Samantha Gailey, Abhery Das, Tim A. Bruckner","doi":"10.1017/thg.2023.49","DOIUrl":"https://doi.org/10.1017/thg.2023.49","url":null,"abstract":"Prior research based on Swedish data suggests that collective optimism, as measured by monthly incidence of suicides, correlates inversely with <jats:italic>selection in utero</jats:italic> against male twins in a population. We test this finding in the US, which reports the highest suicide rate of all high-income countries, and examine whether monthly changes in overall suicides precede changes in the ratio of male twin to male singleton live births. Consistent with prior work, we also examine as a key independent variable, suicides among women aged 15−49 years. We retrieved monthly data on suicides and the ratio of male twin to singleton live births from CDC WONDER, 2003 to 2019, and applied Box-Jenkins iterative time-series routines to detect and remove autocorrelation from both series. Results indicate that a 1% increase in monthly change in overall suicides precedes a 0.005 unit decline in male twin live births ratio 6 months later (coefficient = −.005, <jats:italic>p</jats:italic> value = .004). Results remain robust to use of suicides among reproductive-aged women as the independent variable (coefficient = −.0012, <jats:italic>p</jats:italic> value = .014). Our study lends external validity to prior research and supports the notion that a decline in collective optimism corresponds with greater selection in utero.","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":"3 1","pages":""},"PeriodicalIF":0.9,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138687265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between Dysmenorrhea and Risk of Epilepsy in East Asian Populations: A Bidirectional Two-Sample Mendelian Randomization Study","authors":"Yuehan Ren, Junning Zhang, Tong Chen, Jiaqin Chen, Yan Liao, Tingxiu Liu, Liangliang Yang, Chang Liu, Xinmin Liu, Baoqin Liu","doi":"10.1017/thg.2023.48","DOIUrl":"https://doi.org/10.1017/thg.2023.48","url":null,"abstract":"Dysmenorrhea is associated with epilepsy. Existing evidence is mostly limited to observational studies, which are liable to confounding and bias. This study investigated the causal relevance of dysmenorrhea on epilepsy using Mendelian randomization (MR). We extracted instrumental variants for dysmenorrhea and epilepsy from published genomewide association study data, focusing on individuals of East Asian descent. A comprehensive suite of MR estimations and sensitivity analyses was performed to ensure the robustness of the findings. Each outcome database was analyzed separately in both directions. For dysmenorrhea and epilepsy, 7 and 3 genetic variants respectively were selectively extracted as instrumental variants. The results suggest that dysmenorrhea is causally associated with an elevated risk of epilepsy (inverse variance weighted [IVW]: <jats:italic>OR</jats:italic> = 1.26; 95% CI [1.07, 1.47]; <jats:italic>p</jats:italic> = 4.42 × 10<jats:sup>−3</jats:sup>); conversely, no strong evidence was found to corroborate that epilepsy exerts a causal effect on the incidence of dysmenorrhea (IVW: <jats:italic>OR</jats:italic> = 1.04; 95% CI [0.82, 1.33]; <jats:italic>p</jats:italic> = .72). These findings provide novel insights into the causal relationship between dysmenorrhea and epilepsy, which may have implications for clinical decision-making in patients with epilepsy and dysmenorrhea.","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":"3 1","pages":""},"PeriodicalIF":0.9,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138687261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond Twinship: Unraveling Societal Biases: A Review of Nancy L. Segal, Gay Fathers, Twin Sons: The Citizenship Case That Captured the World","authors":"Hila Segal","doi":"10.1017/thg.2023.39","DOIUrl":"https://doi.org/10.1017/thg.2023.39","url":null,"abstract":"","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":"34 19","pages":""},"PeriodicalIF":0.9,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138603709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GWAS of Dizygotic Twinning in an Enlarged Australian Sample of Mothers of DZ Twins.","authors":"Scott D Gordon, David L Duffy, David C Whiteman, Catherine M Olsen, Kerrie McAloney, Jessica M Adsett, Natalie A Garden, Simone M Cross, Susan E List-Armitage, Joy Brown, Jeffrey J Beck, Hamdi Mbarek, Sarah E Medland, Grant W Montgomery, Nicholas G Martin","doi":"10.1017/thg.2023.45","DOIUrl":"https://doi.org/10.1017/thg.2023.45","url":null,"abstract":"<p><p>Female fertility is a complex trait with age-specific changes in spontaneous dizygotic (DZ) twinning and fertility. To elucidate factors regulating female fertility and infertility, we conducted a genome-wide association study (GWAS) on mothers of spontaneous DZ twins (MoDZT) versus controls (3273 cases, 24,009 controls). This is a follow-up study to the Australia/New Zealand (ANZ) component of that previously reported (Mbarek et al., 2016), with a sample size almost twice that of the entire discovery sample meta-analysed in the previous article (and five times the ANZ contribution to that), resulting from newly available additional genotyping and representing a significant increase in power. We compare analyses with and without male controls and show unequivocally that it is better to include male controls who have been screened for recent family history, than to use only female controls. Results from the SNP based GWAS identified four genomewide significant signals, including one novel region, <i>ZFPM1</i> (Zinc Finger Protein, FOG Family Member 1), on chromosome 16. Previous signals near <i>FSHB</i> (Follicle Stimulating Hormone beta subunit) and <i>SMAD3</i> (SMAD Family Member 3) were also replicated (Mbarek et al., 2016). We also ran the GWAS with a dominance model that identified a further locus <i>ADRB2</i> on chr 5. These results have been contributed to the International Twinning Genetics Consortium for inclusion in the next GWAS meta-analysis (Mbarek et al., in press).</p>","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":" ","pages":"1-12"},"PeriodicalIF":0.9,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138296112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Born Apart, but Raised Together: Twins Delivered in Different Countries/Twin Research Reviews: Hallermann-Streiff Syndrome in Monozygotic (MZ) Twins; Effects of Technology on Conjoined Twin Separation; Reciprocal DIEP Transplantation Between MZ Twins; Guidelines for Multifetal Management/Media Reports: Book by World's Oldest Auschwitz-Birkenau Twin Survivor; Passing of Ian Wilmut; Zhores Medvedev Was an Identical Twin; More Gay Fathers with Twin Sons; Twins and Siblings Admitted to Medical School; First and Fourth Records for Major League Baseball Twins.","authors":"Nancy L Segal","doi":"10.1017/thg.2023.46","DOIUrl":"https://doi.org/10.1017/thg.2023.46","url":null,"abstract":"<p><p>The circumstances and subsequent life events of the first twins to have been born in different countries are examined. Given that both twins were born in the United Kingdom, their common citizenship was never questioned. In contrast, twins born in Canada to a legally married gay transnational couple - composed of one American and one Israeli - were assigned as citizens of different nations and their parents were regarded as if unmarried. This essay is followed by reviews of research on the Hallermann-Streiff syndrome in monozygotic (MZ) twins, the effects of technology on conjoined twin separation, reciprocal deep inferior epigastric perforator (DIEP) transplantation in MZ twins and new guidelines for managing multifetal pregnancies. Finally, media reports on a book by the world's oldest Auschwitz-Birkenau twin survivor, the passing of Dr Ian Wilmut, the identical twinship of Zhores Medvedev, another case of gay fathers with twin sons, twins and siblings admitted to medical school, and the first and fourth records for major league baseball twins are presented.</p>","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":" ","pages":"1-8"},"PeriodicalIF":0.9,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"107592321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic and Familial Influences on Self-Perception in Early Childhood and Self-Esteem in Adulthood: A Cross-Sectional Analysis.","authors":"Riley L Marshall,&nbsp;Lisabeth Fisher DiLalla,&nbsp;Colin R Harbke,&nbsp;Emily C Pali","doi":"10.1017/thg.2023.44","DOIUrl":"https://doi.org/10.1017/thg.2023.44","url":null,"abstract":"<p><p>Self-perception in early childhood and self-esteem in adulthood are related to a variety of aspects of psychological wellbeing. The goal of the present study was to examine genetic and familial influences on self-perception and self-esteem in separate samples of children (153 twin pairs of 5-year-olds) and adults (753 twin pairs between the ages of 25-75 years). Genetic common factor modeling showed that three facets of self-perception (physical competence, peer acceptance, and maternal acceptance) loaded onto a single heritable factor in children. Multilevel modeling showed no effects of self or co-twin sex on self-perception, but authoritative parenting style was negatively related to self-perception in boys. Similarly, in Study 2, with the adult sample, five self-esteem items loaded on a single heritable factor with no effects of co-twin sex on adult self-esteem. Remembered maternal affection, paternal affection, and maternal discipline were positively related to self-esteem in adults; maternal affection was especially significant for women. The reversal in direction of parenting effects between early childhood and adulthood suggests that parents may play different roles in shaping how children and adults think of themselves. These results suggest that self-perception in childhood and self-esteem in adulthood are both influenced by genetic and environmental factors and that parenting is an important environmental factor for both children and adults.</p>","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":" ","pages":"1-14"},"PeriodicalIF":0.9,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49682795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cap Analysis of Gene Expression Clarifies Transcriptomic Divergence Within Monozygotic Twin Pairs.","authors":"Hirokazu Katoh,&nbsp;Hiroaki Asai,&nbsp;Keiko Takemoto,&nbsp;Rie Tomizawa,&nbsp;Chika Honda,&nbsp;Mikio Watanabe,&nbsp;Tomoyuki Honda","doi":"10.1017/thg.2023.42","DOIUrl":"https://doi.org/10.1017/thg.2023.42","url":null,"abstract":"<p><p>Phenotypic variation is the result of gene expression based on complex interaction between genetic and environmental factors. It is well known that genetic and environmental factors influence gene expression, but our understanding of their relative importance remains limited. To obtain a hint for the understanding of their contributions, we took advantage of monozygotic twins, as they share genetic and shared environmental factors but differ in nonshared factors, such as environmental differences and stochastic factors. In this study, we performed cap analysis of gene expression on three pairs of twins and clustered each individual based on their expression profiles of annotated genes. The dendrogram of annotated gene transcripts showed a monophyletic clade for each twin pair. We also analyzed the expression of retrotransposons, such as human endogenous retroviruses (HERVs) and long interspersed nuclear elements (LINEs), given their abundance in the genome. Clustering analyses demonstrated that HERV and LINE expression diverged even within monozygotic twin pairs. Thus, HERVs and LINEs are more susceptible to nonshared factors than annotated genes. Motif analysis of differentially expressed annotated genes suggests that specificity protein/Krüppel-like factor family transcription factors are involved in the expression divergence of annotated gene influenced by nonshared factors. Collectively, our findings suggest that expressions of annotated genes and retrotransposons are differently regulated, and that the expression of retrotransposons is more susceptible to nonshared factors than annotated genes.</p>","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":" ","pages":"1-8"},"PeriodicalIF":0.9,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41238999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}