Annals of Human Genetics最新文献

{"title":"A splice site variant in TCTN3 underlies an atypical form of orofaciodigital syndrome IV","authors":"Shabir Hussain,&nbsp;Shoaib Nawaz,&nbsp;Hammal Khan,&nbsp;Anushree Acharya,&nbsp;Isabelle Schrauwen,&nbsp;Wasim Ahmad,&nbsp;Suzanne M. Leal","doi":"10.1111/ahg.12462","DOIUrl":"10.1111/ahg.12462","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Orofaciodigital syndrome (OFD) is clinically heterogeneous and is characterized by abnormalities in the oral cavity, facial features, digits, and central nervous system. At least 18 subtypes of the condition have been described in the literature. OFD is caused by variants in several genes with overlapping phenotypes. We studied a consanguineous Pakistani family with two affected siblings with an atypical form of OFD type 4 (OFD4). In addition to the typical features of OFD4 that include limb defects and growth retardation, the siblings displayed rare features of scaphocephaly and seizures. Exome sequencing analysis revealed a novel homozygous splice site variant c.257-1G&gt;A in <i>TCTN3</i> that segregated with disease. This homozygous splice site variant in <i>TCTN3</i> is most likely the underlying cause of the atypical form of OFD4 observed in this family. Our results contribute to the phenotypic spectrum of <i>TCTN3</i> associated ciliopathies and will facilitate better clinical diagnosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"86 6","pages":"291-296"},"PeriodicalIF":1.9,"publicationDate":"2022-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/13/24/AHG-86-291.PMC9804382.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10823074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel splicing variant in GALNS in mucopolysaccharidosis IVA and the necessity of re-evaluating primer sequences","authors":"Sang-Mi Kim,&nbsp;Eu Seon Noh,&nbsp;Jong-Ho Park,&nbsp;Hyung-Doo Park,&nbsp;Soo-Youn Lee,&nbsp;Ja-Hyun Jang,&nbsp;Sung Yoon Cho","doi":"10.1111/ahg.12483","DOIUrl":"10.1111/ahg.12483","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <p>Mucopolysaccharidosis type IVA (MPS IVA; Morquio syndrome type A) is an autosomal recessive disorder caused by defects in the lysosomal hydrolase N-acetylgalactosamine-6-sulfatase (<i>GALNS</i>) gene, leading to progressive systemic skeletal dysplasia. Early diagnosis and early intervention with enzyme replacement therapy are crucial for improving outcomes in these patients. However, a relatively high number of patients are genetically undiagnosed due to high allelic heterogeneity and the absence of robust functional evidence for most variants of the <i>GALNS</i> gene. Herein, we report a novel intronic variant identified with RNA analysis and an allele dropout (ADO) event caused by a common benign variant in the primer-binding site in a Korean boy with MPS IVA.</p>\u0000 \u0000 <p>A 28-month-old boy presented with pectus carinatum, kyphoscoliosis, and joint hypermobility with multiple skeletal dysplasia involving the vertebrae and hip joint. Total urinary glycosaminoglycans were elevated with a predominant keratan sulfate fraction, and GALNS (EC 3.1.6.4) activity was significantly decreased in leukocytes. Sanger sequencing was performed; however, only one heterozygous intronic variant with uncertain clinical significance, c.566+3A &gt; T (p.(?)), was identified. As the patient exhibited clinical and biochemical features of MPS IVA, we conducted whole genome sequencing (WGS) of the patient and his family to clarify the molecular diagnosis. WGS revealed a compound heterozygous genotype, c.1019G &gt; A (p.(Gly340Asp)) and c.566+3A &gt; T (p.(?)), in the <i>GALNS</i> gene. On mRNA sequencing, c.566+3A &gt; T, was confirmed to cause exon 5 skipping and a premature stop codon. With subsequent investigation, we discovered that the variant, c.1019G &gt; A, was undetected on initial sequencing because of ADO due to a common benign variant (rs3859024:G &gt; C) at the primer annealing location.</p>\u0000 \u0000 <p>We present a novel intronic variant with a splicing defect in the <i>GALNS</i> gene and suggest that clinicians review primer sequences in cases not diagnosed on Sanger sequencing before progressing to diagnostic steps such as WGS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"86 6","pages":"361-368"},"PeriodicalIF":1.9,"publicationDate":"2022-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40421604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Applicability of the IrisPlex system for eye color prediction in an admixed population from Argentina","authors":"Diana María Hohl,&nbsp;Rebeca González,&nbsp;Gabriela Paula Di Santo Meztler,&nbsp;Jessica Patiño-Rico,&nbsp;Cristina Dejean,&nbsp;Sergio Avena,&nbsp;María De Los Ángeles Gutiérrez,&nbsp;Cecilia Inés Catanesi","doi":"10.1111/ahg.12480","DOIUrl":"10.1111/ahg.12480","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <p>Eye color prediction based on an individual's genetic information is of interest in the field of forensic genetics. In recent years, researchers have studied different genes and markers associated with this externally visible characteristic and have developed methods for its prediction. The IrisPlex represents a validated tool for homogeneous populations, though its applicability in populations of mixed ancestry is limited, mainly regarding the prediction of intermediate eye colors. With the aim of validating the applicability of this system in an admixed population from Argentina (n = 302), we analyzed the six single nucleotide variants used in that multiplex for eye color and four additional SNPs, and evaluated its prediction ability. We also performed a genotype–phenotype association analysis. This system proved to be useful when dealing with the extreme ends of the eye color spectrum (blue and brown) but presented difficulties in determining the intermediate phenotypes (green), which were found in a large proportion of our population. We concluded that these genetic tools should be used with caution in admixed populations and that more studies are required in order to improve the prediction of intermediate phenotypes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"86 6","pages":"297-327"},"PeriodicalIF":1.9,"publicationDate":"2022-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40706536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GR-α and GR-β mRNA levels in peripheral blood mononuclear cells of acute myelitis patients can assist in the identification of glucocorticoid sensitivity and are correlated with glucocorticoid therapeutic effect","authors":"Bolin Tang,&nbsp;Jun Han,&nbsp;Fen Wang,&nbsp;Xiang Li,&nbsp;Chaoyang Zhao","doi":"10.1111/ahg.12472","DOIUrl":"10.1111/ahg.12472","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <p>Acute myelitis (AM) is a rare neuro-immune spinal cord disease. This study sought to explore the transcription level of glucocorticoid (GC) receptors α and β (GR-α/GR-β) in peripheral blood mononuclear cells (PBMCs) and their correlation with GC efficacy and sensitivity in AM patients. AM patients were grouped into the GC-sensitive group (<i>N</i> = 80) and GC-refractory group (<i>N</i> = 67). The GR-α and GR-β mRNA levels in PBMCs were detected. The differentiating value of GR-α, GR-β, and GR-α + GR-β on GC sensitivity and resistance in AM patients was assessed. The independent correlation between GR-α and GR-β mRNA levels and GC sensitivity in AM patients,t and the correlation between GR-α and GR-β mRNA levels and spinal function after GC treatment were analyzed. GR-α mRNA level in PBMCs of GC-refractory patients was lower than that of GC-sensitive patients, while GR-β mRNA level was higher than that of GC-sensitive patients. GR-α + GR-β mRNA had a high diagnostic value for GC sensitivity and resistance in AM patients (area under the ROC curve = 0.881, sensitivity = 79.1%, specificity = 85.0%). GR-α and GR-β mRNA levels were independently correlated with GC sensitivity. GR-α and GR-β mRNA levels were correlated with the spinal function of AM patients after GC treatment. Overall, GR-α and GR-β mRNA levels in PBMCs of AM patients can assist in the identification of GC sensitivity and are correlated with GC efficacy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"86 5","pages":"268-277"},"PeriodicalIF":1.9,"publicationDate":"2022-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40178381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using potential variable to study gene–gene and gene–environment interaction effects with genetic model uncertainty","authors":"Xiaonan Hu,&nbsp;Zhen Meng","doi":"10.1111/ahg.12470","DOIUrl":"10.1111/ahg.12470","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <p>One of the critical issues in genetic association studies is to evaluate the risk of a disease associated with gene–gene or gene–environment interactions. The commonly employed procedures are derived by assigning a particular set of scores to genotypes. However, the underlying genetic models of inheritance are rarely known in practice. Misspecifying a genetic model may result in power loss. By using some potential genetic variables to separate the genotype coding and genetic model parameter, we construct a model-embedded score test (MEST). Our test is free of assumption of gene–environment independence and allows for covariates in the model. An effective sequential optimization algorithm is developed. Extensive simulations show the proposed MEST is robust and powerful in most of scenarios. Finally, we apply the proposed method to rheumatoid arthritis data from the Genetic Analysis Workshop 16 to further investigate the potential interaction effects.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"86 5","pages":"257-267"},"PeriodicalIF":1.9,"publicationDate":"2022-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"62795854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DRD4 polymorphism associated with greater positive affect in response to negative and neutral social stimuli","authors":"T. Lee Gilman,&nbsp;Matthew T. Ford,&nbsp;Aaron M. Jasnow,&nbsp;Karin G. Coifman","doi":"10.1111/ahg.12471","DOIUrl":"10.1111/ahg.12471","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <p>Despite the robustness of <i>DRD4</i> polymorphism associations with brain-based behavioral characteristics in candidate gene research, investigations have minimally explored associations between these polymorphisms and emotional responses. In particular, the prevalent single nucleotide polymorphism (SNP) -521C/T (rs1800955) in the promoter region of <i>DRD4</i> remains unexplored relative to emotions. Here, two independent samples were evaluated using different emotion elicitation tasks involving social stimuli: Study 1 (<i>N</i> = 120) evoked positive and negative emotional responses to validated film clips; Study 2 (<i>N</i> = 122) utilized Cyberball to simulate social rejection and acceptance. Across studies, C/C individuals self-reported higher mean positive affect scores using Likert scales versus T carrier individuals, selectively when presented with neutral or negative (but not positive) social stimuli. The consistent findings across these two studies supports a functional consequence of this <i>DRD4</i> SNP on emotion processing during changing social contexts. Continued investigation will help clarify if a C/C genotype enhances positive emotions under negative circumstances, or if the presence of the T allele reduces positive emotions, and how rs1800955 behavioral associations might generalize across different demographics. Future studies could also reveal if this SNP interacts with other changing environmental conditions to affect emotional responses, such as social limitations during the COVID-19 pandemic.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"86 4","pages":"218-223"},"PeriodicalIF":1.9,"publicationDate":"2022-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.12471","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48881349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel leaky splice variant in centromere protein J (CENPJ)-associated Seckel syndrome","authors":"Navneesh Yadav,&nbsp;Laxmi Kirola,&nbsp;Thenral S Geetha,&nbsp;Kirti Mittal,&nbsp;Jayarama Kadandale,&nbsp;Yuval Yogev,&nbsp;Ohad S. Birk,&nbsp;Neerja Gupta,&nbsp;Prahlad Balakrishnan,&nbsp;Manisha Jana,&nbsp;Meena Gupta,&nbsp;Madhulika Kabra,&nbsp;Bittianda Kuttapa Thelma","doi":"10.1111/ahg.12469","DOIUrl":"10.1111/ahg.12469","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <p>Primary microcephaly and Seckel syndrome are rare genetically and clinically heterogenous brain development disorders. Several exonic/splicing mutations are reported for these disorders to date, but ∼40% of all cases remain unexplained. We aimed to uncover the genetic correlate(s) in a family of multiple siblings with microcephaly. A novel homozygous intronic variant (NC_000013.10:g.25459823T&gt;C) in <i>CENPJ</i> (13q12) segregating with all four affected male siblings was identified by exome sequencing and validated by targeted linkage approach (logarithm of the odds score 1.8 at θ 0.0). RT-PCR of <i>CENPJ</i> in affected siblings using their EBV derived cell lines showed aberrant transcripts suggestive of exon skipping confirmed by Sanger sequencing. Significantly reduced wild type transcript/protein in the affected siblings having the splice variant indicates a leaky gene expression of pathological relevance. Based on known <i>CENPJ</i> function, assessing for mitotic alterations revealed defect in centrosome duplication causing mono/multicentrosome(s) at prophase, delayed metaphase, and unequal chromosomal segregation in patient cells. Clinical features witnessed in this study expand the spectrum of <i>CENPJ</i>-associated primary microcephaly and Seckel syndrome. Furthermore, besides the importance of regulatory variants in classical monogenic disorders these findings provide new insights into splice site biology with possible implications for ASO-based therapies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"86 5","pages":"245-256"},"PeriodicalIF":1.9,"publicationDate":"2022-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47623842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"No significant association between SNPs in the CLOCK and ADH4 genes and susceptibility to cluster headaches: A systematic review and meta-analysis","authors":"Jiarui Cui,&nbsp;Wei Peng,&nbsp;Ting Yi,&nbsp;Ping Gao,&nbsp;Mingze Zhou,&nbsp;Tianmin Zhu","doi":"10.1111/ahg.12467","DOIUrl":"10.1111/ahg.12467","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The circadian locomotor output cycles kaput (<i>CLOCK</i>) gene and the alcohol dehydrogenase 4 (<i>ADH4</i>) gene are promising candidates for susceptibility to cluster headaches (CH). Associations of the three single nucleotide polymorphisms (SNPs)—<i>CLOCK</i> SNP rs1801260 and <i>ADH4</i> SNPs rs1800759, and rs1126671—with CH were studied previously, but the results were inconsistent.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Associations between the three SNPs (rs1801260, rs1126671, and rs1800759) and CH risk were separately assessed by pooled odds ratios (ORs) along with 95% confidence intervals (95% CIs) based on five different genetic models. Methodological quality was assessed using the Newcastle–Ottawa Quality Assessment Scale (NOS). All statistical analyses were carried out with RevMan 5.3 software.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Eight studies involving 1437 CH patients and 2541 healthy controls were selected for quantitative synthesis, from five studies on <i>CLOCK</i> rs1801260, five on <i>ADH4</i> rs1800759, and three on <i>ADH4</i> rs1126671. Our pooled data did not support associations between the three SNPs (rs1801260 in the <i>CLOCK</i> gene, rs1800759 and rs1126671 in the <i>ADH4</i> gene) and susceptibility to CH (rs1801260: OR 1.10, 95% CI: 0.95–1.28; <i>p</i> = 0.19; rs1800759: OR 1.06, 95% CI: 0.93–1.22; <i>p</i> = 0.37; and rs1126671: OR 1.09, 95% CI: 0.92–1.28; <i>p</i> = 0.32).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We found no significant associations between the three SNPs (rs1801260 in the <i>CLOCK</i> gene and rs1800759 and rs1126671 in the <i>ADH4</i> gene) and the susceptibility to CH across both Caucasian and Asian ethnicities in our meta-analysis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"86 4","pages":"159-170"},"PeriodicalIF":1.9,"publicationDate":"2022-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46264665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and H-type hypertension: A systematic review and meta-analysis","authors":"Shengyu Liao,&nbsp;Shuxia Guo,&nbsp;Rulin Ma,&nbsp;Jia He,&nbsp;Yizhong Yan,&nbsp;Xianghui Zhang,&nbsp;Xinping Wang,&nbsp;Boyu Cao,&nbsp;Heng Guo","doi":"10.1111/ahg.12468","DOIUrl":"10.1111/ahg.12468","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>The polymorphism of methylenetetrahydrofolate reductase (<i>MTHFR</i>) gene <i>C677T</i> has been linked to H-type hypertension. But the conclusion remained controversial. To elucidate this issue, we performed a comprehensive meta-analysis to analyze the <i>MTHFR C677T</i> polymorphism and H-type hypertension.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and methods</h3>\u0000 \u0000 <p>The English and Chinese databases were systematically searched to identify relevant studies until November 2020. RevMan 5.3 and Stata 12.0 software were used for meta-analysis. The odds ratio (ORs) and 95% confidence intervals (95% CIs) were used to assess the relationship between the <i>MTHFR C677T</i> polymorphism and H-type hypertension.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 14 studies involving 1769 cases and 1443 controls were included. The meta-analysis results showed the association between <i>MTHFR C677T</i> polymorphism and H-type hypertension with the homozygous codominant model (OR = 3.30, 95% CI = 1.94–5.60), heterozygous codominant model (OR = 2.34, 95% CI = 1.53–3.58), dominant model (OR = 1.79, 95% CI = 1.33–2.41), recessive model (OR = 2.70, 95% CI = 1.73–4.21),and the allelic model (OR = 1.82, 95% CI = 1.41–2.35). All <i>p</i>-values were less than 0.05. Therefore, <i>MTHFR C677T</i> polymorphism has a positive correlation with the risk of H-type hypertension. Among them, TT mutation has the greatest impact on the activity of this enzyme, which causes Hcy to rise and leads to H-type hypertension.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In summary, our results provide sufficient data to support the hypothesis that the <i>MTHFR C677T</i> polymorphism is related to H-type hypertension susceptibility.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"86 5","pages":"278-289"},"PeriodicalIF":1.9,"publicationDate":"2022-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42753093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic and environmental correlational structure among metabolic syndrome endophenotypes","authors":"Stacey S. Cherny,&nbsp;Frances M. K. Williams,&nbsp;Gregory Livshits","doi":"10.1111/ahg.12465","DOIUrl":"10.1111/ahg.12465","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <p>Metabolic syndrome (MetS) is diagnosed by the presence of high scores on three or more metabolic traits, including systolic and diastolic blood pressure (SBP, DBP), glucose and insulin levels, cholesterol and triglyceride (TG) levels, and central obesity. A diagnosis of MetS is associated with increased risk of cardiovascular disease and type 2 diabetes. The components of MetS have long been demonstrated to have substantial genetic components, but their genetic overlap is less well understood. The present paper takes a multi-prong approach to examining the extent of this genetic overlap. This includes the quantitative genetic and additive Bayesian network modeling of the large TwinsUK project and examination of the results of genome-wide association study (GWAS) of UK Biobank data through use of LD score regression and examination of the number of genes and pathways identified in the GWASes which overlap across MetS traits. Results demonstrate a modest genetic overlap, and the genetic correlations obtained from TwinsUK and UK Biobank are nearly identical. However, these correlations imply more genetic dissimilarity than similarity. Furthermore, examination of the extent of overlap in significant GWAS hits, both at the gene and pathway level, again demonstrates only modest but significant genetic overlap. This lends support to the idea that in clinical treatment of MetS, treating each of the components individually may be an important way to address MetS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"86 5","pages":"225-236"},"PeriodicalIF":1.9,"publicationDate":"2022-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9913712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}