Annals of Human Genetics最新文献

{"title":"Population stratification correction using Bayesian shrinkage priors for genetic association studies","authors":"Zilu Liu,&nbsp;Asuman S. Turkmen,&nbsp;Shili Lin","doi":"10.1111/ahg.12527","DOIUrl":"10.1111/ahg.12527","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Population stratification (PS) is a major source of confounding in population-based genetic association studies of quantitative traits. Principal component regression (PCR) and linear mixed model (LMM) are two commonly used approaches to account for PS in association studies. Previous studies have shown that LMM can be interpreted as including all principal components (PCs) as random-effect covariates. However, including all PCs in LMM may dilute the influence of relevant PCs in some scenarios, while including only a few preselected PCs in PCR may fail to fully capture the genetic diversity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and methods</h3>\u0000 \u0000 <p>To address these shortcomings, we introduce Bayestrat—a method to detect associated variants with PS correction under the Bayesian LASSO framework. To adjust for PS, Bayestrat accommodates a large number of PCs and utilizes appropriate shrinkage priors to shrink the effects of nonassociated PCs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Simulation results show that Bayestrat consistently controls type I error rates and achieves higher power compared to its non-shrinkage counterparts, especially when the number of PCs included in the model is large. As a demonstration of the utility of Bayestrat, we apply it to the Multi-Ethnic Study of Atherosclerosis (MESA). Variants and genes associated with serum triglyceride or HDL cholesterol are identified in our analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>The automatic and self-selection features of Bayestrat make it particularly suited in situations with complex underlying PS scenarios, where it is unknown a priori which PCs are potential confounders, yet the number that needs to be considered could be large in order to fully account for PS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"87 6","pages":"302-315"},"PeriodicalIF":1.9,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.12527","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41103337","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":"Application of real-time PCR–based multicolor melting curve with automatic analysis system in pregestational and prenatal thalassemia diagnoses","authors":"Xue-Wei Tang,&nbsp;Fan Jiang,&nbsp;Jian Li,&nbsp;Xiao-Mei Lin,&nbsp;Jian-Ying Zhou,&nbsp;Jun-Hui Wan,&nbsp;Lian-Dong Zuo,&nbsp;Yan-Xia Qu,&nbsp;Fa-Tao Li,&nbsp;Gui-Lan Chen,&nbsp;Dong-Zhi Li","doi":"10.1111/ahg.12531","DOIUrl":"10.1111/ahg.12531","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>To evaluate the value of the real-time PCR–based multicolor melting curve analysis (MMCA) with an automatic analysis system used in a mass thalassemia screening and prenatal diagnosis program.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 18,912 peripheral blood samples from 9456 couples and 1150 prenatal samples were detected by MMCA assay. All prenatal samples were also tested by a conventional method. Samples with unknown melting peaks, unusual peak height ratios between a wild allele and a mutant allele, or a discordant phenotype-genotype match were further studied by using multiplex ligation–dependent probe amplification (MLPA) or Sanger sequencing. All MMCA results were automatically analyzed and manually checked. The consistency between MMCA assay and conventional methods among prenatal samples was investigated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Except for initiation codon (T &gt; G) (HBB:c.2T &gt; G), all genotypes of thalassemia inside the scope of conventional methods were detected by MMCA assay. Additionally, 27 carriers with 10 rare HBB variants, 13 with α fusion gene, 1 with a rare deletion in α globin gene, and 1 with rare HBA variant were detected by using MMCA assay.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>MMCA can be an alternative approach used in routine thalassemia carrier screening and prenatal diagnosis for its high throughput, sufficient stability, low cost, and easy operation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"87 6","pages":"316-325"},"PeriodicalIF":1.9,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41106717","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":"Histone modification: Biomarkers and potential therapies in colorectal cancer","authors":"Xin An,&nbsp;Xiaohua Lan,&nbsp;Zizhen Feng,&nbsp;Xiaohong Li,&nbsp;Qisheng Su","doi":"10.1111/ahg.12528","DOIUrl":"10.1111/ahg.12528","url":null,"abstract":"<p>The complex mechanism of colorectal cancer development is closely associated with epigenetic modifications and is caused by overexpression and/or inactivation of oncogenes. Histone modifying enzymes catalyze histone modifications to alter gene expression, which plays a crucial role in the development and progression of colorectal cancer. Currently, there is more frequent study on histone acetylation, methylation, and phosphorylation, and their mechanisms in colorectal cancer development are clearer. This article elaborates on the role of histone modification in epigenetics in colorectal cancer development and discusses recent advances in using it as biomarkers and therapeutic targets for the treatment of colorectal cancer. The review aims to demonstrate the significant role of histone modification as a new therapeutic target in colorectal cancer and provides insights into the novel diagnostic and therapeutic options it offers.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"87 6","pages":"274-284"},"PeriodicalIF":1.9,"publicationDate":"2023-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.12528","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10243763","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":"Genetic architecture of adiposity measures among Asians: Findings from GWAS","authors":"Tripti Agarwal,&nbsp;Tanica Lyngdoh,&nbsp;Rajesh Khadgawat,&nbsp;Dorairaj Prabhakaran,&nbsp;Giriraj Ratan Chandak,&nbsp;Gagandeep Kaur Walia","doi":"10.1111/ahg.12526","DOIUrl":"10.1111/ahg.12526","url":null,"abstract":"<p>Adiposity has gradually become a global public threat over the years with drastic increase in the attributable deaths and disability adjusted life years (DALYs). Given an increased metabolic risk among Asians as compared to Europeans for any given body mass index (BMI) and considering the differences in genetic architecture between them, the present review aims to summarize the findings from genome-wide scans for various adiposity indices and related anthropometric measures from Asian populations. The search for related studies, published till February 2022, were made on PubMed and GWAS Catalog using search strategy built with relevant keywords joined by Boolean operators. It was recorded that out of a total of 47 identified studies, maximum studies are from Korean population (<i>n</i> = 14), followed by Chinese (<i>n</i> = 7), and Japanese (<i>n</i> = 6). Nearly 200 loci have been identified for BMI, 660 for height, 16 for weight, 28 for circumferences (waist and hip), 32 for ratios (waist hip ratio [WHR] and thoracic hip ratio [THR]), 5 for body fat, 16 for obesity, and 28 for adiposity-related blood markers among Asians. It was observed that though, most of the loci were unique for each trait, there were 3 loci in common to BMI and WHR. Apart from validation of variants identified in European setting, there were many novel loci discovered in Asian populations. Notably, 125 novel loci form Asian studies have been reported for BMI, 47 for height, 5 for waist circumference, and 2 for adiponectin level to the existing knowledge of the genetic framework of adiposity and related measures. It is necessary to examine more advanced adiposity measures, specifically of relevance to abdominal adiposity, a major risk factor for cardiometabolic disorders among Asians. Moreover, in spite of being one continent, there is diversity among different ethnicities across Asia in terms of lifestyle, climate, geography, genetic structure and consequently the phenotypic manifestations. Hence, it is also important to consider ethnic specific studies for identifying and validating reliable genetic variants of adiposity measures among Asians.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"87 6","pages":"255-273"},"PeriodicalIF":1.9,"publicationDate":"2023-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.12526","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10164904","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 heterozygous truncating variant in the AGO1 gene in an Iranian family with schizophrenia as an unreported symptom","authors":"Atefeh Mir,&nbsp;Erfan Khorram,&nbsp;Yongjun Song,&nbsp;Hane Lee,&nbsp;Mohammad Amin Tabatabaiefar","doi":"10.1111/ahg.12524","DOIUrl":"10.1111/ahg.12524","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <p>Intellectual disability (ID) and autism spectrum disorders (ASDs) are the most common developmental disorders in humans. Combined, they affect between 3% and 5% of the population. Although high-throughput genomic methods are rapidly increasing the pool of ASD genes, many cases remain idiopathic. <i>AGO1</i> is one of the less-known genes related to ID/ASD. This gene encodes a core member protein of the RNA-induced silencing complex, which suppresses mRNA expression through cleavage, degradation, and/or translational repression. Generally, patients with defects in the <i>AGO1</i> gene manifest varying degrees of ID, speech delay, and autistic behaviors. Herein, we used whole-exome sequencing (WES) to investigate an Iranian family with two affected members one of whom manifested ID and autism and the other showed borderline ID and schizophrenia. WES analysis identified a novel heterozygous truncating variant (NM_012199.5:c.1298G &gt; A, p.Trp433Ter) in the <i>AGO1</i> gene that co-segregated with the phenotypes using Sanger sequencing. Moreover, the structural analysis showed that due to this variant, two critical domains (Mid and PIWI) of the AGO1 protein have been lost, which has a detrimental effect on the protein's function and structure. To the best of our knowledge, schizophrenia has not been reported in patients with <i>AGO1</i> deficiency, which is a novel phenotypic finding that expands the <i>AGO1</i>-related behavioral disorders. Moreover, this study's findings determined that patients with the same variant in the <i>AGO1</i> gene may show heterogeneity in manifested phenotypes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"87 6","pages":"295-301"},"PeriodicalIF":1.9,"publicationDate":"2023-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10011777","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":"Novel GALT variations and genetic spectrum in Turkish population with the correlation of genotype and phenotype","authors":"Irem Kalay,&nbsp;Cagri Gulec,&nbsp;Mehmet Cihan Balcı,&nbsp;Guven Toksoy,&nbsp;Gulden Gokcay,&nbsp;Seher Basaran,&nbsp;Mubeccel Demirkol,&nbsp;Zehra Oya Uyguner","doi":"10.1111/ahg.12523","DOIUrl":"10.1111/ahg.12523","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Classic galactosemia (OMIM#230400) is an autosomal recessive inborn error of carbohydrate metabolism caused by a deficiency of the galactose-1-phosphate-uridyl-transferase enzyme encoded by the <i>GALT</i> gene. Even though a galactose-restricted diet efficiently resolves the acute complications, it is insufficient to prevent long-term complications regarding speech defects, intellectual functioning, premature ovarian failure, cataract, hepatomegaly, dysarthria, ataxia, and tremor. Seventy-seven patients who were genetically diagnosed with classic galactosemia were included in this cohort. Identified novel variants were classified based on their predicted effect on the GALT function. Further, potential genotype–phenotype correlations were investigated via statistical analysis. In total, 18 different sequence variants were identified, including four novels (c.200delG/p.(Arg67Profs^*19), c.533T&gt;G/ p.(Met178Arg), c.708_709delGT/p.(Ser236Argfs^*30), c.467C&gt;A/p.(Ser156^*)). Jaundice was the most common short-term finding with 80% (61/77). Even with early diagnosis, intellectual disability is encountered with 36% (27/74) of the long-term complications. Patients with biallelic missense variants have a significantly higher prevalence of cataracts (OR: 17.9). Longitudinal observations showed attenuation of cataracts and hepatomegaly. This study has shown the <i>GALT</i> variation spectrum of the Turkish population with a 30-year retrospective cohort, submitting a significant contribution to the genotype/phenotype correlation in galactosemia. This study also highlights the cost-effective importance of Sanger sequencing in the diagnosis of single-gene metabolic diseases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"87 6","pages":"285-294"},"PeriodicalIF":1.9,"publicationDate":"2023-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9977277","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":"Reassessing the association of MUC5B with survival in idiopathic pulmonary fibrosis","authors":"Siyang Cai,&nbsp;Richard J. Allen,&nbsp;Louise V. Wain,&nbsp;Frank Dudbridge","doi":"10.1111/ahg.12522","DOIUrl":"10.1111/ahg.12522","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <p>A variant in the mucin 5B gene (<i>MUC5B</i>) is strongly associated with the risk of idiopathic pulmonary fibrosis. However, the same variant is associated with increased survival time. Previous work suggested that this may be explained by index event bias, with the true effect being to decrease survival. Here, we reassessed this claim using more recent methods and datasets. We found that the statistical assumptions of the previous analysis did not hold, and instead, we applied recent methods of corrected weighted least squares, MR-RAPS and Slope-hunter to both the previous data and an updated consortium meta-analysis. However, these analyses did not yield robust evidence for increased or decreased survival. In simulations of a true effect of decreased survival, we did not observe any realistic scenario in which index event bias led to an observed effect of increased survival. We therefore regard as unsafe the claim that <i>MUC5B</i> has a true effect of decreased survival. Alternative explanations should be sought to explain the observed association with increased survival.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"87 5","pages":"248-253"},"PeriodicalIF":1.9,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.12522","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10053687","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":"Functional characterization of a rare pathogenic variant c.875G > A, p.(Cys292Tyr) in COMP","authors":"Lan Yin,&nbsp;Yingchuan Zhu,&nbsp;Wenhao Jiang,&nbsp;Yue Song,&nbsp;Yilu Lu,&nbsp;Dachang Tao,&nbsp;Yunqiang Liu,&nbsp;Yongxin Ma","doi":"10.1111/ahg.12521","DOIUrl":"10.1111/ahg.12521","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The protein encoded by the cartilage oligomeric matrix protein (<i>COMP</i>) gene is a noncollagenous extracellular matrix (ECM) protein that is important for chondrocyte formation and growth. Variations in the <i>COMP</i> gene cause pseudoachondroplasia (PSACH), which is mainly characterized by short-limbed dwarfing in the clinic.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To characterize the function of a rare pathogenic variant in the <i>COMP</i> gene (c.875G &gt; A, p.Cys292Tyr).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials &amp; Methods</h3>\u0000 \u0000 <p>We performed 3D structural analysis, in vitro expression analysis, and immunofluorescence to characterize the effects of the variant on protein structure, expression, and cellular localization respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Variation modeling showed that the interactions between amino acids were changed after the variation, and there were 31 changes in the secondary structure of mutant COMP (MT-COMP). Western blot showed that the intracellular quantity of MT-COMP was higher than the wild-type COMP (WT-COMP). Cellular immunofluorescence results showed that WT-COMP was less abundant and homogenously distributed in cells, while the MT-COMP accumulated in the cytoplasm.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Herein, we report a variant of <i>COMP</i> in a Chinese family with PSACH. We have shown that the rare missense variant, <i>COMP</i> c.875G &gt; A, previously reported in ClinVar and identified in our patient, results in excessive accumulation of mutant protein in the cytoplasm, and is therefore pathogenic.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Through in silico and experimental analyses, we provide evidence that <i>COMP</i> c.875G &gt; A is the likely cause of PSACH in a Chinese family.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"87 5","pages":"241-247"},"PeriodicalIF":1.9,"publicationDate":"2023-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10046593","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":"Uncovering cilia function in glial development","authors":"Rachel M. Bear,&nbsp;Tamara Caspary","doi":"10.1111/ahg.12519","DOIUrl":"10.1111/ahg.12519","url":null,"abstract":"<p>Primary cilia play critical roles in regulating signaling pathways that underlie several developmental processes. In the nervous system, cilia are known to regulate signals that guide neuron development. Cilia dysregulation is implicated in neurological diseases, and the underlying mechanisms remain poorly understood. Cilia research has predominantly focused on neurons and has overlooked the diverse population of glial cells in the brain. Glial cells play essential roles during neurodevelopment, and their dysfunction contributes to neurological disease; however, the relationship between cilia function and glial development is understudied. Here we review the state of the field and highlight the glial cell types where cilia are found and the ciliary functions that are linked to glial development. This work uncovers the importance of cilia in glial development and raises outstanding questions for the field. We are poised to make progress in understanding the function of glial cilia in human development and their contribution to neurological diseases.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"88 1","pages":"27-44"},"PeriodicalIF":1.9,"publicationDate":"2023-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.12519","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9754660","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":"Pitfalls of predicting age-related traits by polygenic risk scores","authors":"Valentina Escott-Price,&nbsp;Karl Michael Schmidt","doi":"10.1111/ahg.12520","DOIUrl":"10.1111/ahg.12520","url":null,"abstract":"<p>Polygenic risk scores (PRS) are a method increasingly used to capture the combined effect of genome-wide significant variants and those which individually do not show genome-wide significant association but are likely to contribute to the risk of developing diseases. However, their practical use incurs complications and inconsistencies that so far limit their clinical applicability. The aims of the present review are to discuss the PRS for age-related diseases and to highlight pitfalls and limitations of PRS prediction accuracy due to ageing and mortality effects. We argue that the PRS is widely used but the individual's PRS values differ substantially depending on the number of genetic variants included, the discovery GWAS and the method employed to generate them. Moreover, for neurodegenerative disorders, although an individual's genetics do not change with age, the actual score depends on the age of the sample used in the discovery GWAS and is likely to reflect the individual's disease risk at this particular age. Improvement of PRS prediction accuracy for neurodegenerative disorders will come from two sides, both the precision of clinical diagnoses, and a careful attention to the age distribution in the underlying samples and validation of the prediction in longitudinal studies.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"87 5","pages":"203-209"},"PeriodicalIF":1.9,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.12520","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10053150","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}