Article
Biochemical Research Methods
Luca Denti, Parsoa Khorsand, Paola Bonizzoni, Fereydoun Hormozdiari, Rayan Chikhi
Summary: Structural variants (SVs) contribute to sequence variability in genomes and are significant in human genomics and precision medicine. However, due to the complexities of the human genome, SV discovery in individuals has been challenging. The introduction of low-error long-read sequencing technologies, such as PacBio HiFi, may provide a solution to these challenges.
Article
Cell Biology
Valentina Siino, Ashfaq Ali, Giulia Accardi, Anna Aiello, Mattia E. Ligotti, Sergio Mosquim Junior, Giuseppina Candore, Calogero Caruso, Fredrik Levander, Sonya Vasto
Summary: The study of healthy human aging is crucial for understanding the molecular mechanisms behind aging and preventing age-related disorders. In this study, an unbiased mass spectrometry-based approach was used to investigate age-related protein changes in a healthy Sicilian plasma cohort. The findings confirmed previously known proteins associated with age and discovered novel proteins that could be a unique signature for healthy aging.
Article
Cell Biology
Mariana Andrawus, Lital Sharvit, Noga Touitou, Batia Lerrer, Haim Y. Cohen, Gil Atzmon
Summary: Copy number variations (CNV) play a significant role in genome variability and have been associated with aging and pregnancy physiology. By studying CNVs in pregnant mice, researchers have found that most of the selected CNVs showed an opposite trend during pregnancy and post-partum. Additionally, significant differential expression was observed in the nearby genes of the candidate CNVs. This study highlights the importance of using pregnancy as a model for aging and reveals the mechanisms and similarities between pregnancy and aging.
Article
Biochemistry & Molecular Biology
Thomas F. Eleveld, Chaimaa Bakali, Paul P. Eijk, Phylicia Stathi, Lianne E. Vriend, Pino J. Poddighe, Bauke Ylstra
Summary: Large-scale chromosomal deletions are common in cancer and confer an oncogenic advantage, but the oncogenic drivers behind these deletions are difficult to identify. This study introduced a novel CRISPR-Cas9 technique to engineer large-scale deletions and create isogenic cell line models, successfully inducing deletions in neuroblastoma cell lines. The technique may provide valuable insights into the role of large-scale deletions in tumor development and growth.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biotechnology & Applied Microbiology
Shinji Sasaki, Youko Miki, Takayuki Ibi, Hiroyuki Wakaguri, Yuichi Yoshida, Yoshikazu Sugimoto, Yutaka Suzuki
Summary: A study identified a CNV associated with calf mortality, affecting susceptibility to infectious diseases. CNVR_221 homozygotes had lower complement activity and higher risk allele frequency in dead calves with infectious diseases.
Article
Clinical Neurology
Elif Irem Sarihan, Eduardo Perez-Palma, Lisa-Marie Niestroj, Douglas Loesch, Miguel Inca-Martinez, Andrea R. V. R. Horimoto, Mario Cornejo-Olivas, Luis Torres, Pilar Mazzetti, Carlos Cosentino, Elison Sarapura-Castro, Andrea Rivera-Valdivia, Elena Dieguez, Victor Raggio, Andres Lescano, Vitor Tumas, Vanderci Borges, Henrique B. Ferraz, Carlos R. Rieder, Artur F. Schumacher-Schuh, Bruno L. Santos-Lobato, Carlos Velez-Pardo, Marlene Jimenez-Del-Rio, Francisco Lopera, Sonia Moreno, Pedro Chana-Cuevas, William Fernandez, Gonzalo Arboleda, Humberto Arboleda, Carlos E. Arboleda-Bustos, Dora Yearout, Cyrus P. Zabetian, Timothy A. Thornton, Timothy D. O'Connor, Dennis Lal, Ignacio F. Mata
Summary: Parkinson's disease patients from Latino descent show enrichment of copy number variants affecting known Parkinson's disease genes, with PRKN showing the strongest association. Additionally, 5.6% of early-onset patients carried a copy number variant on PRKN. This study provides insights into the genetic complexity of Parkinson's disease in this understudied population.
MOVEMENT DISORDERS
(2021)
Article
Psychiatry
Xavier Caseras, George Kirov, Kimberley M. Kendall, Elliott Rees, Sophie E. Legge, Matthew Bracher-Smith, Valentina Escott-Price, Kevin Murphy
Summary: The study revealed that carriers of rare copy number variants associated with schizophrenia showed reduced surface area, increased cortical thickness, and heightened thickness covariance across gyri in the brain. These changes were predominantly found in frontal and parietal areas and were driven by a limited number of rare risk alleles. The heterogeneity in the effects of rare risk alleles suggests potential different neurobiological pathways into the phenotype of schizophrenia.
BRITISH JOURNAL OF PSYCHIATRY
(2021)
Article
Genetics & Heredity
Thomas Eggermann, Florian Kraft, Eva Lausberg, Katrin Ergezinger, Erdmute Kunstmann
Summary: This study identified a family with a 132 bp deletion within the KCNQ1OT1 gene, which is associated with growth retardation when paternally transmitted but results in a normal phenotype when maternally inherited. Comparisons with cases from the literature helped to determine the functional relevance of this microdeletion within the paternal imprinting center 2 affecting the KCNQ1OT1 gene.
JOURNAL OF MEDICAL GENETICS
(2021)
Article
Genetics & Heredity
Man Jin Kim, Sungyoung Lee, Hongseok Yun, Sung Im Cho, Boram Kim, Jee-Soo Lee, Jong Hee Chae, Choonghyun Sun, Sung Sup Park, Moon-Woo Seong
Summary: This study developed a novel diagnostic tool, CCR-CNV, for the identification of exonic copy number variations (CNVs) with high confidence. Compared to other well-known CNV tools, CCR-CNV showed higher sensitivity and specificity. However, its low covered region, positive predictive value, and high false discovery rate limit its use in clinical settings. The combined use of CCR-CNV with existing CNV tools improves its performance.
GENETICS IN MEDICINE
(2022)
Article
Biochemical Research Methods
Junping Li, Lin Gao, Yusen Ye
Summary: The researchers developed a control-free method called HiSV for identifying large-scale structural variations from Hi-C samples. HiSV achieved superior accuracy and sensitivity through evaluations on simulated data sets and cancer cell lines, and effectively captured complex SVs. HiSV can also supplement the results of WGS methods.
PLOS COMPUTATIONAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Gregg W. C. Thomas, Richard J. Wang, Jelena Nguyen, R. Alan Harris, Muthuswamy Raveendran, Jeffrey Rogers, Matthew W. Hahn
Summary: The study analyzed patterns of CNV mutations in rhesus macaque individuals, finding a low rate of CNV mutations per generation and no correlation between parental age and the number of CNVs passed on to offspring. Rhesus macaques and humans differ in the proportion of segregating deletions, with both species having more segregating deletions than duplications.
MOLECULAR BIOLOGY AND EVOLUTION
(2021)
Article
Biochemical Research Methods
Chirag Jain, Arang Rhie, Nancy F. Hansen, Sergey Koren, Adam M. Phillippy
Summary: Approximately 5-10% of the human genome is inaccessible due to the presence of repetitive sequences. Existing long-read mappers often yield incorrect alignments and variant calls within repetitive sequences. To address this issue, a new long-read mapping method called Winnowmap2 was developed, which is more tolerant of structural variation and more sensitive to paralog-specific variants within repeats.
Article
Biology
Milovan Suvakov, Arijit Panda, Colin Diesh, Ian Holmes, Alexej Abyzov
Summary: CNVpytor is an extension of CNVnator that improves performance and functionality, allowing for filtering, annotation, and merging of CNV calls across multiple samples. Its modular architecture enables use in shared and cloud environments, and data can be exported to JBrowse for visualization and analysis.
Article
Oncology
Bart Vrugt, Michaela B. Kirschner, Mayura Meerang, Kathrin Oehl, Ulrich Wagner, Alex Soltermann, Holger Moch, Isabelle Opitz, Peter J. Wild
Summary: In this study, the suitability of using p16 and MTAP IHC for detecting CDKN2A deletion in pleural mesothelioma was investigated. The results showed that MTAP and p16 IHC had high sensitivity and specificity for detecting any gene loss, and had high concordance with OncoScan CNV arrays.
Article
Biochemical Research Methods
Melivoia Rapti, Yassine Zouaghi, Jenny Meylan, Emmanuelle Ranza, Stylianos E. Antonarakis, Federico A. Santoni
Summary: CoverageMaster (CoM) is a CNV calling algorithm based on depth-of-coverage maps, capable of accurately detecting and visualizing CNVs of any size, supporting the possibility of replacing probe-based methods with coverage-based approaches.
BRIEFINGS IN BIOINFORMATICS
(2022)
Article
Nutrition & Dietetics
Fabian Hellbach, Lucy Sinke, Ricardo Costeira, Sebastian-Edgar Baumeister, Marian Beekman, Panayiotis Louca, Emily R. Leeming, Olatz Mompeo, Sarah Berry, Rory Wilson, Nina Wawro, Dennis Freuer, Hans Hauner, Annette Peters, Juliane Winkelmann, Wolfgang Koenig, Christa Meisinger, Melanie Waldenberger, Bastiaan T. Heijmans, P. Eline Slagboom, Jordana T. Bell, Jakob Linseisen
Summary: This study examined the association between food consumption and DNA methylation and found significant correlations between the methylation level of CpG sites and the consumption of onions and garlic, nuts and seeds, milk, cream, plant oils, butter, and alcoholic beverages. These findings targeted genes relevant to metabolic health.
EUROPEAN JOURNAL OF NUTRITION
(2023)
Article
Geriatrics & Gerontology
Zeyuan Song, Anastasia Gurinovich, Marianne Nygaard, Jonas Mengel-From, Stacy Andersen, Stephanie Cosentino, Nicole Schupf, Joseph Lee, Joseph Zmuda, Svetlana Ukraintseva, Konstantin Arbeev, Kaare Christensen, Thomas Perls, Paola Sebastiani
Summary: We conducted a genome-wide association study of Digit Symbol Substitution Test scores in 4207 family members of the Long Life Family Study (LLFS). The study discovered 18 rare genetic variants associated with processing speed, located near THRB and RARB genes on chromosome 3, which may affect metabolism and cognitive aging.
NEUROBIOLOGY OF AGING
(2023)
Article
Geriatrics & Gerontology
Chaoqun Wang, Xiaolei Han, Yi Dong, Cuicui Liu, Xiaojie Wang, Tingting Hou, Qihua Tan, Yongxiang Wang, Yifeng Du, Chengxuan Qiu
Summary: We investigated the relationship between common WWC1 variants and Alzheimer's disease (AD) and vascular dementia (VaD) in rural older adults in China. Our population-based study utilized data from the baseline assessments of MIND-China. Logistic regression analysis revealed that the C allele of WWC1 rs17070145 was associated with an increased risk of AD, while the CC genotype was associated with an increased risk of VaD, but this association became non-significant when adjusting for stroke history. Additionally, two exonic SNPs, rs3822660 and rs3822659, were found to be in strong linkage disequilibrium (LD) with rs17070145.
NEUROBIOLOGY OF AGING
(2023)
Article
Multidisciplinary Sciences
Laura Lokkegaard Johansen, Mikael Thinggaard, Jesper Hallas, Merete Osler, Kaare Christensen
Summary: A study found that the preference for hormone therapy (HT) changed after the publication of the Women's Health Initiative in 2002. It was discovered that women using HT had a lower mortality rate before 2002, but after 2002 their mortality rate became similar to that of the general population. This indicates that the healthiest users decided to either discontinue HT or switch to local HT based on the changing recommendations.
SCIENTIFIC REPORTS
(2023)
Article
Biotechnology & Applied Microbiology
Afsaneh Mohammadnejad, Mette Soerensen, Jonas Mengel-From, Marianne Nygaard, Maria Timofeeva, Liang He, Signe Bedsted Clemmensen, Ulrich Halekoh, Rikke Hedegaard Dahlrot, Qihua Tan, Jacob V. B. Hjelmborg
Summary: By performing a genome-wide association study on gene expression data from Danish twin pairs, 243 single nucleotide polymorphisms (SNPs) significantly associated with expression of the MGMT gene were identified, including 7 novel cis-eQTLs and 11 suggestive trans-eQTLs. These variations may regulate the function of the MGMT gene and the patient's sensitivity to therapeutic alkylating agents.
Article
Neurosciences
Qingyan Xiang, Stacy L. Andersen, Benjamin Sweigart, Sophia Gunn, Marianne Nygaard, Thomas T. Perls, Paola Sebastiani
Summary: By analyzing the neuropsychological test results in the Long Life Family Study (LLFS), we identified 12 different patterns of cognitive domains and their associations with other risk factors and biomarkers. These findings are crucial for improving our understanding of cognitive aging.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Endocrinology & Metabolism
Rikke Hjortebjerg, Dorthe Almind Pedersen, Jonas Mengel-From, Louise Helskov Jorgensen, Kaare Christensen, Jan Frystyk
Summary: This study measured the concentration of pregnancy-associated plasma protein-A (PAPP-A) in elderly same-sex twins and found that PAPP-A levels increase with age. Additionally, the study revealed a significant genetic component in determining the levels of PAPP-A and stanniocalcin-2 (STC2).
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Medical Informatics
Lijie Wang, Jinling Zhang, Jingtao Wang, Hao Xue, Lin Deng, Fengyuan Che, Xueyuan Heng, Xuejun Zheng, Zilong Lu, Liuqing Yang, Qihua Tan, Yeping Xu, Yanchun Zhang, Xiaokang Ji, Gang Li, Fan Yang, Fuzhong Xue
Summary: This study aimed to develop and validate a nomogram for predicting the overall survival of patients with newly diagnosed grade II/III astrocytoma after surgery. The results showed that the nomogram had good predictive ability and consistency, based on data from different hospitals.
HEALTH INFORMATION SCIENCE AND SYSTEMS
(2023)
Article
Multidisciplinary Sciences
Niels van den Berg, Mar Rodriguez-Girondo, Ingrid K. van Dijk, P. Eline Slagboom, Marian Beekman
Summary: Globally, the lifespan of populations is increasing, but the healthspan is not keeping up. Research shows that longevity runs in families, with each additional long-lived family member increasing the lifespan of study participants. This study investigated whether the healthspan in such families follows a similar pattern and found that an increasing number of long-lived ancestors is associated with up to a decade of healthspan extension. The study also found that members of long-lived families have delayed onset of medication use, multimorbidity, and healthier metabolomic profiles than their partners.
NATURE COMMUNICATIONS
(2023)
Article
Genetics & Heredity
Lisa de las Fuentes, Karen L. M. Schwander, Michael R. Brown, Amy R. Bentley, Thomas W. Winkler, Yun Ju Sung, Patricia B. Munroe, Clint L. Miller, Hugo Aschard, Stella Aslibekyan, Traci M. Bartz, Lawrence F. Bielak, Jin Fang Chai, Ching-Yu Cheng, Rajkumar Dorajoo, Mary F. Feitosa, Xiuqing Guo, Fernando P. Hartwig, Andrea Horimoto, Ivana Kolcic, Elise Lim, Yongmei Liu, Alisa K. Manning, Jonathan Marten, Solomon K. Musani, Raymond Noordam, Sandosh Padmanabhan, Tuomo Rankinen, Melissa A. Richard, Paul M. Ridker, Albert V. Smith, Dina Vojinovic, Alan B. Zonderman, Maris Alver, Mathilde Boissel, Kaare Christensen, Barry I. Freedman, Chuan Gao, Franco Giulianini, Sarah E. Harris, Meian He, Fang-Chi Hsu, Brigitte Kuehnel, Federica Laguzzi, Xiaoyin Li, Leo-Pekka Lyytikainen, Ilja M. Nolte, Alaitz Poveda, Rainer Rauramaa, Muhammad Riaz, Antonietta Robino, Tamar Sofer, Fumihiko Takeuchi, Bamidele O. Tayo, Peter J. van der Most, Niek Verweij, Erin B. Ware, Stefan Weiss, Wanqing Wen, Lisa R. Yanek, Yiqiang Zhan, Najaf Amin, Dan E. Arking, Christie Ballantyne, Eric Boerwinkle, Jennifer A. Brody, Ulrich Broeckel, Archie Campbell, Mickael Canouil, Xiaoran Chai, Yii-Der Ida Chen, Xu Chen, Kumaraswamy Naidu Chitrala, Maria Pina Concas, Ulf de Faire, Renee de Mutsert, H. Janaka de Silva, Paul S. de Vries, Ahn Do, Jessica D. Faul, Virginia Fisher, James S. Floyd, Terrence Forrester, Yechiel Friedlander, Giorgia Girotto, C. Charles Gu, Goeran Hallmans, Sami Heikkinen, Chew-Kiat Heng, Georg Homuth, Steven Hunt, M. Arfan Ikram, David R. Jacobs, Maryam Kavousi, Chiea Chuen Khor, Tuomas O. Kilpelainen, Woon-Puay Koh, Pirjo Komulainen, Carl D. Langefeld, Jingjing Liang, Kiang Liu, Jianjun Liu, Kurt Lohman, Reedik Magi, Ani W. Manichaikul, Colin A. McKenzie, Thomas Meitinger, Yuri Milaneschi, Matthias Nauck, Christopher P. Nelson, Jeffrey R. O'Connell, Nicholette D. Palmer, Alexandre C. Pereira, Thomas Perls, Annette Peters, Ozren Polasek, Olli T. Raitakari, Kenneth Rice, Treva K. Rice, Stephen S. Rich, Charumathi Sabanayagam, Pamela J. Schreiner, Xiao-Ou Shu, Stephen Sidney, Mario Sims, Jennifer A. Smith, John M. Starr, Konstantin Strauch, E. Shyong Tai, Kent D. Taylor, Michael Y. Tsai, Andre G. Uitterlinden, Diana van Heemst, Melanie Waldenberger, Ya-Xing Wang, Wen-Bin Wei, Gregory Wilson, Deng Xuan, Jie Yao, Caizheng Yu, Jian-Min Yuan, Wei Zhao, Diane M. Becker, Amelie Bonnefond, Donald W. Bowden, Richard S. Cooper, Ian J. Deary, Jasmin Divers, Tonu Esko, Paul W. Franks, Philippe Froguel, Christian Gieger, Jost B. Jonas, Norihiro Kato, Timo A. Lakka, Karin Leander, Terho Lehtimaki, Patrik K. E. Magnusson, Kari E. North, Ioanna Ntalla, Brenda Penninx, Nilesh J. Samani, Harold Snieder, Beatrice Spedicati, Pim van der Harst, Henry Voelzke, Lynne E. Wagenknecht, David R. Weir, Mary K. Wojczynski, Tangchun Wu, Wei Zheng, Xiaofeng Zhu, Claude Bouchard, Daniel Chasman, Michele Evans, Ervin R. Fox, Vilmundur Gudnason, Caroline Hayward, Bernardo L. Horta, Sharon L. R. Kardia, Jose Eduardo Krieger, Dennis O. Mook-Kanamori, Patricia A. Peyser, Michael M. Province, Bruce M. Psaty, Igor Rudan, Xueling Sim, Blair H. Smith, Rob M. van Dam, Cornelia M. van Duijn, Tien Yin Wong, Donna K. Arnett, Dabeeru C. Rao, James Gauderman, Ching-Ti Liu, Alanna C. Morrison, Jerome I. Rotter, Myriam Fornage
Summary: This study conducted a genome-wide meta-analysis to investigate the interaction between educational attainment and lipid levels. They identified novel lipid loci that were not previously detected by analyses limited to main genetic effects. The study also highlighted the potential importance of brain-adipose-liver communication in lipid metabolism and identified gene targets that interact with drugs approved by the FDA.
FRONTIERS IN GENETICS
(2023)
Article
Genetics & Heredity
Konstantin G. Arbeev, Svetlana Ukraintseva, Olivia Bagley, Hongzhe Duan, Deqing Wu, Igor Akushevich, Eric Stallard, Alexander Kulminski, Kaare Christensen, Mary F. Feitosa, Jeffrey R. O'Connell, Daniel Parker, Heather Whitson, Anatoliy I. Yashin
Summary: Dysregulation of physiological processes may contribute to the development of Alzheimer's disease, and genes associated with an increase in physiological dysregulation may play a major role in AD onset.
FRONTIERS IN GENETICS
(2023)
Article
Psychology, Multidisciplinary
Susan E. Luczak, Christopher R. Beam, Shandell Pahlen, Morgan Lynch, Matthew Pilgrim, Chandra A. Reynolds, Matthew S. Panizzon, Vibeke S. Catts, Kaare Christensen, Deborah Finkel, Carol E. Franz, William S. Kremen, Teresa Lee, Matt McGue, Marianne Nygaard, Brenda L. Plassman, Keith E. Whitfield, Nancy L. Pedersen, Margaret Gatz
Summary: Research shows that memory can be inherited, and older adults generally have worse memory performance than younger adults. It is still unknown whether the contributions of genetic and environmental factors to verbal episodic memory ability differ at later ages. Analysis of twin data from 12 studies in the IGEMS consortium revealed an increase in inter-individual variance with age, but the specific contributions of genetic and environmental factors could not be determined. Overall, environmental factors, particularly word list learning, have a comparatively significant impact on verbal episodic memory compared to other cognitive domains.
Article
Geriatrics & Gerontology
Giulia Ogliari, Jesper Ryg, Karen Andersen-Ranberg, Lasse Lybecker Scheel-Hincke, Jemima T. Collins, Alison Cowley, Claudio Di Lorito, Vicky Booth, Roelof A. J. Smit, Ralph K. Akyea, Nadeem Qureshi, David A. Walsh, Rowan H. Harwood, Tahir Masud
Summary: This study investigates the longitudinal associations between pain and depressive symptoms in adults. The findings suggest that higher baseline pain intensity is associated with a greater risk of developing significant depressive symptoms in community-dwelling adults, at 2-year follow-up.
EUROPEAN GERIATRIC MEDICINE
(2023)
Article
Geriatrics & Gerontology
Anders Fournaise, Jorgen T. Lauridsen, Soren K. Nissen, Claire Gudex, Mickael Bech, Anna Mejldal, Uffe K. Wiil, Jesper B. Rasmussen, Kristian Kidholm, Lars Matzen, Kurt Espersen, Karen Andersen-Ranberg
Summary: This study aimed to test whether the use of the PATINA tool was associated with changes in health-care use. The results showed that despite having no effect on the primary outcome, the PATINA tool showed other benefits for older adults receiving home-based care.
LANCET HEALTHY LONGEVITY
(2023)