PLoS Genetics最新文献

{"title":"The SynMuvA lin-15A licenses natural transdifferentiation by antagonizing identity safeguarding mechanisms.","authors":"Sarah Frieda Becker, Marie-Charlotte Morin, Julien Lambert, Shashi Kumar Suman, Francesco Nicola Carelli, Alex Appert, Stéphane Roth, Sarah Hoff-Yoessle, Jessica D Medina-Sanchez, Manuela Portoso, Julie Ahringer, Sophie Jarriault","doi":"10.1371/journal.pgen.1012290","DOIUrl":"10.1371/journal.pgen.1012290","url":null,"abstract":"<p><p>The mechanisms that restrict or enable latent cellular plasticity have attracted growing interest over the past decade, with important implications for cancer and regenerative therapies. However, the diversity of both pro- and anti-plasticity mechanisms remains incompletely understood. Here, we identify the THAP domain gene lin-15A as a novel factor involved in the natural rectal-to-neuronal Y-to-PDA transdifferentiation in Caenorhabditis elegans. Our genetic analyses show that lin-15A acts in parallel to previously described plasticity factors. Null mutant suggests that, rather than driving the process, LIN-15A licenses its initiation by antagonizing several chromatin-modifying complexes known to safeguard differentiated cell identities. In addition, our data show that even cells developmentally programmed to undergo transdifferentiation exhibit reprogramming barriers. Interestingly, lin-15A is not a core plasticity factor per se but acts as one specifically in the Y cell context. Together, our findings support a model in which diverse molecular activities coordinate controlled cell identity conversions: plasticity factors function as Drivers, while others like lin-15A, termed here transdifferentiation Licensers, attenuate identity safeguarding mechanisms, thereby facilitating transdifferentiation.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 9","pages":"e1012290"},"PeriodicalIF":3.9,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13641710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149065601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of the m6A methyltransferase Mettl16 in Drosophila development.","authors":"Penghui Song, Lijuan Ma, Dong Yan","doi":"10.1371/journal.pgen.1012317","DOIUrl":"10.1371/journal.pgen.1012317","url":null,"abstract":"<p><p>N6-methyladenosine (m6A), one of the most abundant chemical modifications on RNA, is installed by METTL3 and several other methyltransferases, including METTL16. Although METTL16 has been characterized in several model organisms, its function in Drosophila remains unknown. Here, we show that, unlike in mammals, Drosophila Mettl16 mutants are viable but exhibit multiple developmental and behavioral defects. Both male and female mutants are sterile, with severe gametogenesis defects. Mettl16 mutant germ cells can pass the mitotic and meiotic stages, but are defective in spermatid elongation and individualization. Mettl16-GFP localizes predominantly to the nucleus, and its absence does not impair global protein synthesis in wing disc epithelial cells. MeRIP-Seq analysis indicates that Mettl16 loss affects m6A on only a small subset of transcripts, in contrast to the broad effect of Mettl3. We further demonstrate that Mettl16 interacts with U6 snRNA and is required for its m6A modification. Accordingly, Mettl16 mutants display widespread alterations in alternative splicing. Together, the pleiotropic phenotypes of Mettl16 mutants likely stem from its role in m6A deposition and U6-dependent splicing regulation of specific target transcripts.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 9","pages":"e1012317"},"PeriodicalIF":3.9,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13608003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149041447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Univariate-guided sparse regression for Biobank-scale high-dimensional omics data.","authors":"Joshua Richland, Tuomo Kiiskinen, William Wang, Wenhui Sophia Lu, Balasubramanian Narasimhan, Trevor Hastie, Manuel Rivas, Robert Tibshirani","doi":"10.1371/journal.pgen.1012314","DOIUrl":"10.1371/journal.pgen.1012314","url":null,"abstract":"<p><p>We present a scalable framework for computing polygenic risk scores (PRS) in high-dimensional genomic settings using the recently introduced Univariate-Guided Sparse Regression (uniLasso). UniLasso is a two-stage penalized regression procedure that leverages univariate coefficients and magnitudes to stabilize feature selection and produce sparse predictive models. Building on its theoretical and empirical advantages, we adapt uniLasso for application to the UK Biobank, a population-based repository comprising over one million genetic variants measured on hundreds of thousands of individuals from the United Kingdom. We further extend the framework to incorporate external summary statistics via uniLasso ES (external scores). These signals guide the regression toward variants with prior evidence of association by informing penalty weights and sign constraints. Both uniLasso ES and uniLasso ultimately fit multivariate models using individual-level target data; the external statistics guide, rather than replace, this fitting. Our results demonstrate that uniLasso attains predictive performance comparable to standard Lasso while selecting substantially fewer variants, yielding sparser and potentially more interpretable models. Moreover, it remains competitive with other PRS estimation methods, such as PRS-CS and lassosum2.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 9","pages":"e1012314"},"PeriodicalIF":3.9,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13623159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149031766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL1-mediated m7G modification regulates hair follicle cycle via the HOXC13/FOXN1/DSG4 axis.","authors":"Xinyan Gan, Qiwen Li, Qiuchan Xiong, Denghao Huang, Zizheng Liu, Qi Yin, Shuang Jiang, Takuma Matsubara, Shoichiro Kokabu, Wei Yan, Quan Yuan","doi":"10.1371/journal.pgen.1012307","DOIUrl":"10.1371/journal.pgen.1012307","url":null,"abstract":"<p><p>Rapid hair follicle cycling requires precise fate commitment and differentiation of hair follicle stem cells. While the essential role of transcription factors in establishing cell identity is well recognized, how cells control its protein synthesis to achieve tissue specificity remains unknown. RNA modifications constitute a pivotal layer of post-transcriptional regulation for protein synthesis. Among them, the N7-methylguanosine (m7G) modification has recently emerged as a critical regulator with diverse functional impacts. Here, we reveal a pivotal role of METTL1, the key enzyme for RNA m7G modification, in hair follicle cycle. Conditional knockout of Mettl1 in keratinocytes leads to severe hair follicle developmental dysplasia, impaired regeneration, and disrupted keratinocyte adhesion. Complementarily, keratinocyte-specific knock-in of Mettl1 accelerates hair regeneration. Mechanistically, beyond its effects on tRNAs, METTL1 deficiency destabilizes HOXC13 mRNA through internal m7G modification, which in turn downregulates the HOXC13/FOXN1/DSG4 signaling axis. Our findings establish METTL1-mediated internal mRNA m7G methylation as one of the essential regulatory layers of RNA modification in hair follicle morphogenesis and cycling, operating through the precise post-transcriptional control of a key transcriptional circuit to ensure structural integrity and timely regeneration.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 9","pages":"e1012307"},"PeriodicalIF":3.9,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13596829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149026392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prenatal consequences of GALT deficiency in a rat model of classic galactosemia.","authors":"Shauna A Rasmussen, Catherine M Lemons, Madelyn M Seemiller, Sabrina R Dallas, Milan Cambon Ledesma, Yuhan Wu, Lauren E Anshen, Ashlyn Farnham, Olivia S Garrett, Judith L Fridovich-Keil","doi":"10.1371/journal.pgen.1012276","DOIUrl":"10.1371/journal.pgen.1012276","url":null,"abstract":"<p><p>Classic galactosemia (CG) is a potentially lethal disease that results from profound deficiency of galactose-1-P uridylyltransferase (GALT). Prior reports document elevated galactose metabolites beginning in utero in CG, raising concern that long-term complications in CG might also trace their origins to the prenatal period. However, studies document that elevated galactose metabolites in the postnatal period do not predict later developmental complications, challenging the connection. Here, we explored the relationship between elevated galactose metabolites in utero and fetal outcome using a GALT-null rat model of CG. To modify galactose metabolites in utero, we arranged rat crosses to produce GALT-null pups developing within either a GALT-null or heterozygous dam, and with or without heterozygous siblings. We reasoned that GALT activity present outside the fetus, but within the maternal-fetal compartment, might limit metabolic abnormalities in a developing GALT-null fetus -- and it did. Specifically, while galactose metabolites in GALT-null fetal pups from all crosses remained elevated over controls, the levels varied. When the dam and some siblings were heterozygous, amniotic fluid galactitol from GALT-null fetal pups at GD21 was comparable to the levels reported from second trimester human CG amniotic fluid. When the dam was GALT-null, but some siblings were heterozygous, the median galactitol level in amniotic fluid was 2.45-fold higher. When the dam and all siblings were GALT-null, the median amniotic fluid galactitol level was 5.67-fold higher. GALT-null fetal pups also showed significant growth delay in utero, but only when the dam and all siblings were GALT-null. That growth of GALT-null fetal pups was fully rescued by gestation within a heterozygous dam despite the persistence of moderately elevated galactose metabolites raises the possibility that babies with CG developing within a carrier mother might also be at least partially protected in utero from the adverse consequences of their GALT-deficiency.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 9","pages":"e1012276"},"PeriodicalIF":3.9,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13623136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149018401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bacterial chromosomal gene positioning is likely shaped by selection on both mean and growth-dependent expression.","authors":"Ruiqi Yuan, Jianzhi Zhang","doi":"10.1371/journal.pgen.1012316","DOIUrl":"10.1371/journal.pgen.1012316","url":null,"abstract":"<p><p>In bacteria with circular chromosomes, genes near the replication origin (oriC) are replicated earlier and consequently attain higher copy numbers than genes near the terminus (ter), particularly during rapid growth. Hence, mutations altering a gene's chromosomal position can affect its expression level and be subject to selection. Two non-mutually exclusive hypotheses regarding the target of this selection have been proposed. The mean expression hypothesis (MEH) posits that the target is a gene's average expression across environments, whereas the growth-dependent expression hypothesis (GEH) proposes that the target is the growth dependence of gene expression, quantified by the expression slope-the change in expression level per unit change in growth rate. To test these hypotheses and assess their relative support, we analyze eight multi-environment protein expression datasets from three bacterial species, as well as Escherichia coli promoter strengths measured in two environments. Consistent with both MEH and GEH, we observe a significant decrease in both mean expression and expression slope from oriC to ter in six and four of the eight datasets, respectively. In regression models predicting gene position, the relative contributions of the two hypotheses differ across species. However, even when combined, the two hypotheses explain only a small fraction of chromosomal gene positioning, in part because the replication-dose effect is incompletely offset by compensatory evolution of individual promoter strengths. The positional gradients in mean and growth-dependent expression are disproportionately contributed by genes involved in translation and transcription. We conclude that patterns of bacterial chromosomal gene positioning are consistent with moderate effects of selection on both mean and growth-dependent expression.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 9","pages":"e1012316"},"PeriodicalIF":3.9,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13607872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 analysis of epistasis between nucleotide excision repair and homologous recombination in the recovery of persisters after fluoroquinolone treatment.","authors":"Nashaly Soto-Echevarria, Annabel S Lemma, Mark P Brynildsen","doi":"10.1371/journal.pgen.1012305","DOIUrl":"10.1371/journal.pgen.1012305","url":null,"abstract":"<p><p>Stationary-phase cultures contain high abundances of persisters, which are bacterial cells that are hyper-tolerant to antibiotics due to phenotypic reasons. Fluoroquinolones (FQs) are one of the most effective antibiotic classes for the treatment of non-growing bacteria, such as those found in stationary-phase cultures, and persisters in those populations have been found to survive FQ treatment by repairing the DNA damage caused by the antibiotic rather than by avoiding damage through inactivity. Interestingly, previous work demonstrated that transient growth inhibition after the conclusion of FQ treatment significantly increased persister levels from stationary-phase Escherichia coli populations if recA, a mediator of homologous recombination (HR), or uvrD, a component of nucleotide excision repair (NER), were present. Here, we sought to identify additional epistatic interaction partners in that persister recovery network by deleting DNA repair enzymes known to interact with RecA or UvrD. We found that uvrA, uvrB, and mfd also epistatically interact with recA in FQ persister recovery, whereas recB and recC are additional epistatic interaction partners of uvrD. While these results indicated that HR and NER can contribute to persister recovery, different combinations of genetic mutants suggested that the phenomenon is more nuanced than compensation for loss of one repair pathway by another. Specifically, loss of recA had farther reaching epistatic consequences than loss of other HR genes, and loss of uvrD had a greater impact on the network than any other NER gene. Delving deeper into the roles of RecA and UvrD, we found that the recombination function of RecA, via RecA(N304D), and helicase function of UvrD, via UvrD(R284A), were required for their participation in FQ persister recovery. Collectively, the data presented here deepen understanding of the roles of HR and NER machinery in the recovery FQ persisters and further emphasize the important roles of RecA and UvrD in this phenomenon.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 9","pages":"e1012305"},"PeriodicalIF":3.9,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13592689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual contributions of Xrp1 to genome integrity through the DNA damage response and cell competition.","authors":"Chaitali Khan, Nasser M Rusan, Nicholas E Baker","doi":"10.1371/journal.pgen.1012309","DOIUrl":"10.1371/journal.pgen.1012309","url":null,"abstract":"<p><p>Model organisms may help understand how p53 suppresses tumorigenesis in mammals. In Drosophila, the primary transcriptional target of p53 is the gene encoding the bZip AT-hook protein Xrp1, which is another transcription factor. We report that Xrp1 mediates multiple functions of p53 in the DNA damage response (DDR), contributing to p53-dependent gene transcription and DNA damage-induced apoptosis. In addition to this role as a p53 effector, a p53-independent role for Xrp1 in cell competition has been described. Cell competition can remove cells whose genome has been altered by DNA damage and repair. During cell competition, Xrp1 is induced by RpS12, which acts as a sensor of defective ribosome biogenesis. In irradiated discs, p53-independent RpS12-dependent Xrp1 function began as the DDR came to an end, and was even more prominent if p53 function was reduced. Such p53 inhibition resulted in persistence of DNA damage after irradiation, revealed by γH2Av accumulation. Thus, Xrp1 limited the accumulation of abnormal cells resulting from genotoxicity through both the acute, p53-dependent DDR, and also a later mechanism consistent with cell competition removing cells where DNA repair did not restore the normal genome. Both these processes might contribute to the tumor suppressor function of p53 in mammals.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 9","pages":"e1012309"},"PeriodicalIF":3.9,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13588501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149002776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying shared polygenic risk across cancers.","authors":"Jiaqi Hu, Maiyier Muheyati, Leqi Xu, Andrew DeWan, Hongyu Zhao","doi":"10.1371/journal.pgen.1012308","DOIUrl":"10.1371/journal.pgen.1012308","url":null,"abstract":"<p><strong>Background: </strong>Shared genetic susceptibility across cancers has been reported but is generally modest at the genome-wide level. Whether such shared polygenic risk exhibits structured convergence at regional or functional levels remains unclear. We investigated shared genetic risk across cancers by integrating local genetic correlation analyses with cross-cancer polygenic risk score (PRS) associations.</p><p><strong>Methods: </strong>We estimated pairwise local genetic correlations across 16 specific cancers and one pan-cancer phenotype using SUPERGNOVA. Genome regions harboring multiple cancers with mutually correlated local genetic effects were annotated using genetic correlations with non-cancer phenotypes and associations from the GWAS Catalog. In parallel, cross-cancer PRS associations were evaluated, and significant cancer pairs were identified. Genome-wide PRSs for selected pairs were further decomposed into pleiotropy-informed and pathway-specific components to assess functional enrichment of shared polygenic risk.</p><p><strong>Results: </strong>Genome-wide genetic correlation analyses identified 20 significantly correlated cancer pairs, whereas local analyses revealed 82 regions with shared genetic signals across 66 cancer pairs. Five regions exhibited mutually correlated cancer clusters, with enrichment in functional domains such as inflammatory functions. Cross-cancer PRS analyses identified five cancer pairs with shared polygenic risk. Decomposition of PRSs indicated that these cross-cancer associations were enriched in specific pleiotropy groups and immune-related pathways rather than reflecting diffuse genome-wide overlap.</p><p><strong>Conclusion: </strong>Our findings demonstrate that although shared genetic susceptibility across cancers is limited at the genome-wide level, it becomes evident when examined at regional and polygenic scales. Integrating local genetic correlation and PRS decomposition analyses reveals structured patterns of shared genetic risk, providing a framework for investigating cross-cancer polygenic susceptibility.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 9","pages":"e1012308"},"PeriodicalIF":3.9,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149002761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond years of schooling: Genetic associations across educational milestones in two Norwegian cohorts.","authors":"Eirik Haugland Kvalvik, Yunpeng Wang, Kristine Beate Walhovd, Torkild Hovde Lyngstad, Ole Røgeberg","doi":"10.1371/journal.pgen.1012310","DOIUrl":"10.1371/journal.pgen.1012310","url":null,"abstract":"<p><p>Although educational attainment is heritable, years-of-education (EduYears) measures are not designed to show how genetic associations vary across discrete educational milestones. In the Norwegian Mother, Father and Child Cohort Study (MoBa; N = 120,527) and the Norwegian Twin Registry (N = 8,910), we combined genome-wide association studies (GWAS), polygenic indices (PGIs), and twin models to characterize genetic associations with high-school completion and bachelor's, master's, and doctoral attainment. In transition-specific analyses conditional on prior attainment, observed-scale common-variant heritability (h2SNP) and PGI discrimination followed an inverse-U pattern, peaking for progression from high-school completion to attainment of at least a bachelor's degree (HS → BSc + ; h2SNP ≈ 0.14; R2Tjur ≈ 0.05) and declining at postgraduate transitions. Genetic correlations (rg) with large-scale GWAS of EduYears (EA4) and intelligence were high at earlier transitions but lower at later ones (for EA4, rg ≈ 0.92 at HS → BSc+ and ≈ 0.38 at MSc → PhD). In cumulative analyses of attained status in the full cohort, the point-estimate gap between twin- and SNP-based heritability narrowed from ≈ 0.38 at high-school completion to ≈ 0.11 at PhD, while genetic overlap was lower for distant than adjacent milestones (rg ≈ 0.71 for high-school completion versus PhD and ≈ 0.92 for adjacent milestones). Sensitivity analyses using an alternative intelligence GWAS and additional PGIs showed similar transition-specific trajectories. At the doctoral transition, estimates were obtained among individuals who had attained at least a master's degree, so attenuation there must be interpreted in light of selection and range restriction. Because EduYears converts distinct credentials and progression steps into a single numerical scale, estimates expressed per additional year should not be interpreted as though one year has the same meaning across the educational sequence. Milestone-preserving analyses make that hidden structure visible and sharpen the interpretation of education GWAS and PGIs.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 9","pages":"e1012310"},"PeriodicalIF":3.9,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13596786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148992074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}