{"title":"Implementing genomic newborn screening as an effective public health intervention: sidestepping the hype and criticism.","authors":"Jan M Friedman","doi":"10.1038/s41525-024-00451-7","DOIUrl":"10.1038/s41525-024-00451-7","url":null,"abstract":"","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"9 1","pages":"70"},"PeriodicalIF":4.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11659425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Seok-Ho Yu, Francyne Kubaski, Gavin Arno, Whitney Phinney, Tim C Wood, Heather Flanagan-Steet, Laura M Pollard, Richard Steet
{"title":"Functional assessment of IDUA variants of uncertain significance identified by newborn screening.","authors":"Seok-Ho Yu, Francyne Kubaski, Gavin Arno, Whitney Phinney, Tim C Wood, Heather Flanagan-Steet, Laura M Pollard, Richard Steet","doi":"10.1038/s41525-024-00457-1","DOIUrl":"10.1038/s41525-024-00457-1","url":null,"abstract":"<p><p>With the expansion of newborn screening efforts for MPS disorders, the number of identified variants of uncertain significance in IDUA continues to increase. To better define functional consequences of identified IDUA variants, we developed a HEK293-based expression platform that can be used to determine the relative specific activity of variant α-iduronidases by combining a fluorescence-based activity assay and semi-quantitative western blotting. We employed the current platform to characterize over thirty different IDUA variants, including known benign and pathogenic variants, as well as multiple variants of uncertain significance identified through newborn screening. This analysis allowed the stratification of variant enzymes based on their relative specific activity, and uncovered distinct effects of the different variants on enzyme folding, processing, and stability. While relative specific activity serves as a useful first-level test for enzyme function, our observations reinforce the need for secondary analyses of enzyme function to fully assess variant pathogenicity.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"9 1","pages":"68"},"PeriodicalIF":4.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11659309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Letizia Vestito, Julius O B Jacobsen, Susan Walker, Valentina Cipriani, Nomi L Harris, Melissa A Haendel, Christopher J Mungall, Peter Robinson, Damian Smedley
{"title":"Efficient reinterpretation of rare disease cases using Exomiser.","authors":"Letizia Vestito, Julius O B Jacobsen, Susan Walker, Valentina Cipriani, Nomi L Harris, Melissa A Haendel, Christopher J Mungall, Peter Robinson, Damian Smedley","doi":"10.1038/s41525-024-00456-2","DOIUrl":"10.1038/s41525-024-00456-2","url":null,"abstract":"<p><p>Whole genome sequencing has transformed rare disease research; however, 50-80% of rare disease patients remain undiagnosed after such testing. Regular reanalysis can identify new diagnoses, especially in newly discovered disease-gene associations, but efficient tools are required to support clinical interpretation. Exomiser, a phenotype-driven variant prioritisation tool, fulfils this role; within the 100,000 Genomes Project (100kGP), diagnoses were identified after reanalysis in 463 (2%) of 24,015 unsolved patients after previous analysis for variants in known disease genes. However, extensive manual interpretation was required. This led us to develop a reanalysis strategy to efficiently reveal candidates from recent disease gene discoveries or newly designated pathogenic/likely pathogenic variants. Optimal settings to highlight new candidates from Exomiser reanalysis were identified with high recall (82%) and precision (88%) when including Exomiser's automated ACMG/AMP classifier, which correctly converted 92% of variants from unknown significance to pathogenic/likely pathogenic. In conclusion, Exomiser efficiently reinterprets previously unsolved cases.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"9 1","pages":"65"},"PeriodicalIF":4.7,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11655964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Iftekhar A Showpnil, Maria E Hernandez Gonzalez, Swetha Ramadesikan, Mohammad Marhabaie, Allison Daley, Leeran Dublin-Ryan, Matthew T Pastore, Umamaheswaran Gurusamy, Jesse M Hunter, Brandon S Stone, Dennis W Bartholomew, Kandamurugu Manickam, Anthony R Miller, Richard K Wilson, Rolf W Stottmann, Daniel C Koboldt
{"title":"Long-read genome sequencing resolves complex genomic rearrangements in rare genetic syndromes.","authors":"Iftekhar A Showpnil, Maria E Hernandez Gonzalez, Swetha Ramadesikan, Mohammad Marhabaie, Allison Daley, Leeran Dublin-Ryan, Matthew T Pastore, Umamaheswaran Gurusamy, Jesse M Hunter, Brandon S Stone, Dennis W Bartholomew, Kandamurugu Manickam, Anthony R Miller, Richard K Wilson, Rolf W Stottmann, Daniel C Koboldt","doi":"10.1038/s41525-024-00454-4","DOIUrl":"10.1038/s41525-024-00454-4","url":null,"abstract":"<p><p>Long-read sequencing can often overcome the deficiencies in routine microarray or short-read technologies in detecting complex genomic rearrangements. Here we used Pacific Biosciences circular consensus sequencing to resolve complex rearrangements in two patients with rare genetic anomalies. Copy number variants (CNVs) identified by clinical microarray -chr8p deletion and chr8q duplication in patient 1, and interstitial deletions of chr18q in patient 2-were suggestive of underlying rearrangements. Long-read genome sequencing not only confirmed these CNVs but also revealed their genomic structures. In patient 1, we resolved a novel recombinant chromosome 8 (Rec8)-like rearrangement with a 3.43 Mb chr8q terminal duplication that was linked to a 7.25-8.21 Mb chr8p terminal deletion. In patient 2, we uncovered a novel complex rearrangement involving a 1.17 Mb rearranged segment and four interstitial deletions ranging from 9 bp to 12.39 Mb. Our results underscore the diversity of clinically relevant structural rearrangements and the power of long-read sequencing in unraveling their nuanced architectures.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"9 1","pages":"66"},"PeriodicalIF":4.7,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11655636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ashlesha Gogate, Kiran Kaur, Raida Khalil, Mahmoud Bashtawi, Mary Ann Morris, Kimberly Goodspeed, Patricia Evans, Maria H Chahrour
{"title":"The genetic landscape of autism spectrum disorder in an ancestrally diverse cohort.","authors":"Ashlesha Gogate, Kiran Kaur, Raida Khalil, Mahmoud Bashtawi, Mary Ann Morris, Kimberly Goodspeed, Patricia Evans, Maria H Chahrour","doi":"10.1038/s41525-024-00444-6","DOIUrl":"10.1038/s41525-024-00444-6","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) comprises neurodevelopmental disorders with wide variability in genetic causes and phenotypes, making it challenging to pinpoint causal genes. We performed whole exome sequencing on a modest, ancestrally diverse cohort of 195 families, including 754 individuals (222 with ASD), and identified 38,834 novel private variants. In 68 individuals with ASD (~30%), we identified 92 potentially pathogenic variants in 73 known genes, including BCORL1, CDKL5, CHAMP1, KAT6A, MECP2, and SETD1B. Additionally, we identified 158 potentially pathogenic variants in 120 candidate genes, including DLG3, GABRQ, KALRN, KCTD16, and SLC8A3. We also found 34 copy number variants in 31 individuals overlapping known ASD loci. Our work expands the catalog of ASD genetics by identifying hundreds of variants across diverse ancestral backgrounds, highlighting convergence on nervous system development and signal transduction. These findings provide insights into the genetic underpinnings of ASD and inform molecular diagnosis and potential therapeutic targets.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"9 1","pages":"62"},"PeriodicalIF":4.7,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11618689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hao Huang, Russel Keathley, Ujin Kim, Horacio Cardenas, Ping Xie, Jianjun Wei, Ernst Lengyel, Kenneth P Nephew, Guangyuan Zhao, Zhen Fu, Emma L Barber, Masha Kocherginsky, Victoria Bae-Jump, Bin Zhang, Daniela Matei
{"title":"Comparative transcriptomic, epigenomic and immunological analyses identify drivers of disparity in high-grade serous ovarian cancer.","authors":"Hao Huang, Russel Keathley, Ujin Kim, Horacio Cardenas, Ping Xie, Jianjun Wei, Ernst Lengyel, Kenneth P Nephew, Guangyuan Zhao, Zhen Fu, Emma L Barber, Masha Kocherginsky, Victoria Bae-Jump, Bin Zhang, Daniela Matei","doi":"10.1038/s41525-024-00448-2","DOIUrl":"10.1038/s41525-024-00448-2","url":null,"abstract":"<p><p>Black women face the highest mortality-to-incidence ratio from high grade serous ovarian cancer (HGSOC). This study investigated biological differences in HGSOC tumors from Black vs. White women. HGSOC from 35 Black and 31 White patients were analyzed by Infinium Methyation-EPIC array and RNA sequencing. 191 CpG sites were differentially methylated (FDR < 0.05, β value change> 10%) and 277 genes were differentially expressed (FDR < 0.05). Gene Ontology identified enriched pathways related to DNA damage response, p53/apoptosis signaling, and cholesterol/lipid metabolism directly connected with genes like INSR, FOXA1 and FOXB1. INSR and FOXA1 knockdown enhanced cisplatin sensitivity and inhibited cell proliferation and colony formation. Tumors from Black patients were infiltrated by fewer CD4+ naïve and regulatory T-cells. Overall, differences in DNA methylation, transcriptomic profiles and immune cell infiltration were detected in tumors from Black vs. White patients. Further investigation is warranted into how these differences may affect treatment response and outcomes in Black women.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"9 1","pages":"64"},"PeriodicalIF":4.7,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11612190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Courtney E French, Nancy C Andrews, Alan H Beggs, Philip M Boone, Catherine A Brownstein, Maya Chopra, Janet Chou, Wendy K Chung, Alissa M D'Gama, Ryan N Doan, Darius Ebrahimi-Fakhari, Richard D Goldstein, Mira Irons, Christina Jacobsen, Margaret Kenna, Ted Lee, Jill A Madden, Amar J Majmundar, Nina Mann, Sarah U Morton, Annapurna Poduri, Adrienne G Randolph, Amy E Roberts, Stephanie Roberts, Matthew G Sampson, Diane D Shao, Wanqing Shao, Aditi Sharma, Eliot Shearer, Akiko Shimamura, Scott B Snapper, Siddharth Srivastava, Jay R Thiagarajah, Mary C Whitman, Monica H Wojcik, Shira Rockowitz, Piotr Sliz
{"title":"Hospital-wide access to genomic data advanced pediatric rare disease research and clinical outcomes.","authors":"Courtney E French, Nancy C Andrews, Alan H Beggs, Philip M Boone, Catherine A Brownstein, Maya Chopra, Janet Chou, Wendy K Chung, Alissa M D'Gama, Ryan N Doan, Darius Ebrahimi-Fakhari, Richard D Goldstein, Mira Irons, Christina Jacobsen, Margaret Kenna, Ted Lee, Jill A Madden, Amar J Majmundar, Nina Mann, Sarah U Morton, Annapurna Poduri, Adrienne G Randolph, Amy E Roberts, Stephanie Roberts, Matthew G Sampson, Diane D Shao, Wanqing Shao, Aditi Sharma, Eliot Shearer, Akiko Shimamura, Scott B Snapper, Siddharth Srivastava, Jay R Thiagarajah, Mary C Whitman, Monica H Wojcik, Shira Rockowitz, Piotr Sliz","doi":"10.1038/s41525-024-00441-9","DOIUrl":"10.1038/s41525-024-00441-9","url":null,"abstract":"<p><p>Boston Children's Hospital has established a genomic sequencing and analysis research initiative to improve clinical care for pediatric rare disease patients. Through the Children's Rare Disease Collaborative (CRDC), the hospital offers CLIA-grade exome and genome sequencing, along with other sequencing types, to patients enrolled in specialized rare disease research studies. The data, consented for broad research use, are harmonized and analyzed with CRDC-supported variant interpretation tools. Since its launch, 66 investigators representing 26 divisions and 45 phenotype-based cohorts have joined the CRDC. These studies enrolled 4653 families, with 35% of analyzed cases having a finding either confirmed or under further investigation. This accessible and harmonized genomics platform also supports additional institutional data collections, research and clinical, and now encompasses 13,800+ patients and their families. This has fostered new research projects and collaborations, increased genetic diagnoses and accelerated innovative research via integration of genomics research with clinical care.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"9 1","pages":"60"},"PeriodicalIF":4.7,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11612168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jong Hyeon Ahn, Jihoon G Yoon, Jaeso Cho, Seungbok Lee, Sheehyun Kim, Man Jin Kim, Soo Yeon Kim, Soon-Tae Lee, Kon Chu, Sang Kun Lee, Han-Joon Kim, Jinyoung Youn, Ja-Hyun Jang, Jong-Hee Chae, Jangsup Moon, Jin Whan Cho
{"title":"Implementing genomic medicine in clinical practice for adults with undiagnosed rare diseases.","authors":"Jong Hyeon Ahn, Jihoon G Yoon, Jaeso Cho, Seungbok Lee, Sheehyun Kim, Man Jin Kim, Soo Yeon Kim, Soon-Tae Lee, Kon Chu, Sang Kun Lee, Han-Joon Kim, Jinyoung Youn, Ja-Hyun Jang, Jong-Hee Chae, Jangsup Moon, Jin Whan Cho","doi":"10.1038/s41525-024-00449-1","DOIUrl":"10.1038/s41525-024-00449-1","url":null,"abstract":"<p><p>The global burden of undiagnosed diseases, particularly in adults, is rising due to their significant socioeconomic impact. To address this, we enrolled 232 adult probands with undiagnosed conditions, utilizing bioinformatics tools for genetic analysis. Alongside exome and genome sequencing, repeat-primed PCR and Cas9-mediated nanopore sequencing were applied to suspected short tandem repeat disorders. Probands were classified into probable genetic (n = 128) or uncertain (n = 104) origins. The study found genetic causes in 66 individuals (28.4%) and non-genetic causes in 12 (5.2%), with a longer diagnostic journey for those in the probable genetic group or with pediatric symptom onset, emphasizing the need for increased efforts in these populations. Genetic diagnoses facilitated effective surveillance, cascade screening, drug repurposing, and pregnancy planning. This study demonstrates that integrating sequencing technologies improves diagnostic accuracy, may shorten the time to diagnosis, and enhances personalized management for adults with undiagnosed diseases.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"9 1","pages":"63"},"PeriodicalIF":4.7,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11604660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Achille Vc Manirakiza, Shakuntala Baichoo, Annette Uwineza, Damas Dukundane, Francois Uwinkindi, Edouard Ngendahayo, Fidel Rubagumya, Emmanuel Muhawenimana, Nicaise Nsabimana, Innocent Nzeyimana, Theoneste Maniragaba, Faustin Ntirenganya, Ephrem Rurangwa, Pacifique Mugenzi, Janviere Mutamuliza, Daniel Runanira, Brandon A Niyibizi, Eulade Rugengamanzi, Jeffrey Besada, Sarah M Nielsen, Brianna Bucknor, Robert L Nussbaum, Diane Koeller, Caroline Andrews, Leon Mutesa, Temidayo Fadelu, Timothy R Rebbeck
{"title":"Germline sequence variation in cancer genes in Rwandan breast and prostate cancer cases.","authors":"Achille Vc Manirakiza, Shakuntala Baichoo, Annette Uwineza, Damas Dukundane, Francois Uwinkindi, Edouard Ngendahayo, Fidel Rubagumya, Emmanuel Muhawenimana, Nicaise Nsabimana, Innocent Nzeyimana, Theoneste Maniragaba, Faustin Ntirenganya, Ephrem Rurangwa, Pacifique Mugenzi, Janviere Mutamuliza, Daniel Runanira, Brandon A Niyibizi, Eulade Rugengamanzi, Jeffrey Besada, Sarah M Nielsen, Brianna Bucknor, Robert L Nussbaum, Diane Koeller, Caroline Andrews, Leon Mutesa, Temidayo Fadelu, Timothy R Rebbeck","doi":"10.1038/s41525-024-00446-4","DOIUrl":"10.1038/s41525-024-00446-4","url":null,"abstract":"<p><p>Cancer genetic data from Sub-Saharan African (SSA) are limited. Patients with female breast (fBC), male breast (mBC), and prostate cancer (PC) in Rwanda underwent germline genetic testing and counseling. Demographic and disease-specific information was collected. A multi-cancer gene panel was used to identify germline Pathogenic Variants (PV) and Variants of Uncertain Significance (VUS). 400 patients (201 with BC and 199 with PC) were consented and recruited to the study. Data was available for 342 patients: 180 with BC (175 women and 5 men) and 162 men with PC. PV were observed in 18.3% fBC, 4.3% PC, and 20% mBC. BRCA2 was the most common PV. Among non-PV carriers, 65% had ≥1 VUS: 31.8% in PC and 33.6% in BC (female and male). Our findings highlight the need for germline genetic testing and counseling in cancer management in SSA.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"9 1","pages":"61"},"PeriodicalIF":4.7,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11586404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Common protein-altering variant in GFAP is associated with white matter lesions in the older Japanese population.","authors":"Yoshihiko Furuta, Masato Akiyama, Naoki Hirabayashi, Takanori Honda, Mao Shibata, Tomoyuki Ohara, Jun Hata, Chikashi Terao, Yukihide Momozawa, Yasuko Tatewaki, Yasuyuki Taki, Shigeyuki Nakaji, Tetsuya Maeda, Kenjiro Ono, Masaru Mimura, Kenji Nakashima, Jun-Ichi Iga, Minoru Takebayashi, Toshiharu Ninomiya","doi":"10.1038/s41525-024-00431-x","DOIUrl":"10.1038/s41525-024-00431-x","url":null,"abstract":"<p><p>The genetic architecture of white matter lesions (WMLs) in Asian populations has not been well-characterized. Here, we performed a genome-wide association study (GWAS) to identify loci associated with the WML volume. Brain MRI and DNA samples were collected from 9479 participants in the Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD). The GWAS confirmed three known WML-associated loci (SH3PXD2A, GFAP, and TRIM47). The lead variant of GFAP was a common missense variant (p.D295N) in East Asians. Meta-GWAS using the publicly available summary statistics of UK Biobank identified one previously unreported locus 6q23.2 (SLC2A12). Integration with expression quantitative trait locus data implied the newly identified locus affects SLC2A12 expression. The effect sizes of 20 lead variants at the WML-associated loci were moderately correlated between JPSC-AD and UK Biobank. These results indicate that the alteration in GFAP protein caused by the common missense variant in East Asians influences the WML volume.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"9 1","pages":"59"},"PeriodicalIF":4.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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