Article
Multidisciplinary Sciences
Yuchang Wu, Xiaoyuan Zhong, Yunong Lin, Zijie Zhao, Jiawen Chen, Boyan Zheng, James J. Li, Jason M. Fletcher, Qiongshi Lu
Summary: The study introduces a statistical framework to estimate direct and indirect genetic effects using GWAS summary statistics, successfully applied to birth weight and educational attainment. Genetic effects of educational attainment show distinct patterns of genetic correlations with 45 complex traits.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Ziyi Xiong, Xingjian Gao, Yan Chen, Zhanying Feng, Siyu Pan, Haojie Lu, Andre G. G. Uitterlinden, Tamar Nijsten, Arfan Ikram, Fernando Rivadeneira, Mohsen Ghanbari, Yong Wang, Manfred Kayser, Fan Liu
Summary: Standard genome-wide association studies (GWASs) analyze single traits at a time, but many human phenotypes are composed of multiple correlated traits. The authors introduce a method called C-GWAS, which combines GWAS summary statistics of multiple potentially correlated traits and shows increased statistical power compared to other methods. Applying C-GWAS to facial GWAS data, they identify loci with multi-trait effects on facial morphology and replicate these findings in additional samples.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Valeriya Chekanova, Julien Vaucher, Pedro Marques-Vidal
Summary: This study aimed to assess the association between genetic markers and hypertension control. Two surveys conducted in Lausanne, Switzerland revealed poor control of hypertension, with older age consistently associated with worse control. However, no associations were found between genetic risk scores or individual SNPs and hypertension control.
SCIENTIFIC REPORTS
(2023)
Article
Computer Science, Information Systems
Harrison G. Zhang, Boris P. Hejblum, Griffin M. Weber, Nathan P. Palmer, Susanne E. Churchill, Peter Szolovits, Shawn N. Murphy, Katherine P. Liao, Isaac S. Kohane, Tianxi Cai
Summary: The ATLAS algorithm is a powerful tool for conducting association testing on probabilistically linked data, with the ability to handle missing variables and avoid false matches, resulting in high power compared to previous methods.
JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION
(2021)
Article
Microbiology
Rebecca T. Batstone, Hanna Lindgren, Cassandra M. Allsup, Laura A. Goralka, Alex B. Riley, Michael A. Grillo, Amy Marshall-Colon, Katy D. Heath
Summary: A goal of modern biology is to develop a predictive understanding of how genomic information generates trait variation in both natural and managed communities. This research investigates the genomic architecture of a symbiotic extended phenotype, partner quality, by studying genetic variation in a model microbial symbiont and host genotypes. It identifies three novel categories of loci that must be considered to build a reliable G -> P map of partner quality.
Article
Infectious Diseases
Kah Yee Tai, Jasbir Dhaliwal, Vinod Balasubramaniam
Summary: The study revealed significant genetic marker differences between populations, indicating varying resistance or susceptibility to malaria. The Mann-Whitney U test proved robust in analyzing genetic markers in large-scale data, offering an alternative method for exploring genetic markers in complex diseases. The findings hold promise for genetic marker analysis and can be replicated for analyzing new data.
Article
Biology
Ryan Sun, Liang Zhu, Yimei Li, Yutaka Yasui, Leslie Robison
Summary: The rapid rise of genetic compendiums in biomedical settings with rich longitudinal disease data has led to a need for tools to analyze genetic data with interval-censored outcomes. This study develops three tests for interval-censored settings, allowing for set-based inference in genetic analysis. Simulation studies demonstrate the advantages of these tests over ad hoc alternatives.
Article
Mathematics
Zheng Xu
Summary: This paper extends methods for testing the association between a continuous response variable and a group of common or rare genetic variants without the need for genotype calling. The proposed NGS data-based methods, derived from a linear model framework, show better statistical power compared to genotype-based methods, with improved performance as sequencing depth increases.
Review
Clinical Neurology
Giulia Di Lazzaro, Francesca Magrinelli, Carlos Estevez-Fraga, Enza M. Valente, Antonio Pisani, Kailash P. Bhatia
Summary: X-linked parkinsonism is a rare genetic disorder characterized by a spectrum of neurological signs, with a complex underlying genetic basis including a variety of causative genes and mutation types. The recognition of phenotypic and genetic heterogeneity in X-linked parkinsonism has important implications for diagnosis, management, and genetic counseling.
MOVEMENT DISORDERS
(2021)
Article
Mathematics
Zheng Xu, Song Yan, Cong Wu, Qing Duan, Sixia Chen, Yun Li
Summary: This study developed NGS data-based methods for association studies, filling the gap in the literature. Simulation studies showed that NGS data-based methods have better performance than genotype-based methods for handling binary and count responses, especially when sequencing depth is low.
Article
Plant Sciences
Mita Khatun, Md Mamun Monir, Xiangyang Lou, Jun Zhu, Haiming Xu
Summary: This study analyzed four ear traits associated with corn production and identified significant genetic factors and environmental effects that contribute to the phenotypic variations of these traits. The results also suggested that different genotype combinations in different geographical regions may be more effective and hybrid-line variety breeding could have a greater potential to improve ear traits.
Article
Ophthalmology
Michalis Georgiou, Lucia Finocchio, Kaoru Fujinami, Yu Fujinami-Yokokawa, Gianni Virgili, Omar A. Mahroo, Andrew R. Webster, Michel Michaelides
Summary: This study examines the genetic and clinical features of X-linked retinoschisis (XLRS). The findings reveal a high phenotypic variability in XLRS, with relative preservation of the fovea and best-corrected visual acuity until late adulthood. However, the disease course is slow-progressing, posing challenges for early intervention and therapeutic trials.
Editorial Material
Ecology
Ivan Paz-Vinas, Evelyn L. Jensen, Laura D. Bertola, Martin F. Breed, Brian K. Hand, Margaret E. Hunter, Francine Kershaw, Deborah M. Leigh, Gordon Luikart, Joachim Mergeay, Joshua M. Miller, Charles B. Van Rees, Gernot Segelbacher, Sean Hoban
Summary: The study by Millette et al. did not find consistent anthropogenic effects on animal genetic diversity worldwide. However, reexamination of the data revealed limitations related to genetic markers and scale which may lead to misinterpretations with conservation implications. Suggestions were provided for improving future macrogenetic studies.
Article
Biology
Olivier David, Arnaud Le Rouzic, Christine Dillmann
Summary: This study investigates optimization of sampling designs for pedigrees and association studies, highlighting the importance of considering mutation effects in sampling pedigrees with many generations. Optimized designs can improve joint estimation of breeding values and locus effects, especially in scenarios with low sample sizes and simple genetic architectures for traits.
Article
Biotechnology & Applied Microbiology
Shuai Wang, James B. Meigs, Josee Dupuis
Summary: Advancements in statistical methods and sequencing technology have led to numerous novel discoveries in human genetics in the past two decades. We propose an efficient score test to analyze a multinomial trait in family samples, in the context of genome-wide association/sequencing studies. Both proposed tests have correct type-I error rate and similar power.
Article
Biochemistry & Molecular Biology
Haloom Rafehi, Cherie Green, Kiymet Bozaoglu, Greta Gillies, Martin B. Delatycki, Paul J. Lockhart, Ingrid E. Scheffer, Melanie Bahlo
Summary: This study identified a family with myotonic dystrophy type 2 caused by an expansion of a specific STR, which could be detected through screening of WGS datasets. The findings have implications for diagnosis and genetic counseling.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Antony Kaspi, Michael S. Hildebrand, Victoria E. Jackson, Ruth Braden, Olivia van Reyk, Tegan Howell, Simone Debono, Mariana Lauretta, Lottie Morison, Matthew J. Coleman, Richard Webster, David Coman, Himanshu Goel, Mathew Wallis, Gabriel Dabscheck, Lilian Downie, Emma K. Baker, Bronwyn Parry-Fielder, Kirrie Ballard, Eva Harrold, Shaun Ziegenfusz, Mark F. Bennett, Erandee Robertson, Longfei Wang, Amber Boys, Simon E. Fisher, David J. Amor, Ingrid E. Scheffer, Melanie Bahlo, Angela T. Morgan
Summary: This study identified new candidate genes associated with childhood apraxia of speech (CAS) through genome sequencing and bioinformatic analysis. The findings highlight the roles of chromatin organization and gene regulation in CAS, and confirm co-expression of CAS-related genes during brain development.
MOLECULAR PSYCHIATRY
(2023)
Article
Genetics & Heredity
Haloom Rafehi, Justin Read, David J. Szmulewicz, Kayli C. Davies, Penny Snell, Liam G. Fearnley, Liam Scott, Mirja Thomsen, Greta Gillies, Kate Pope, Mark F. Bennett, Jacob E. Munro, Kathie J. Ngo, Luke Chen, Mathew J. Wallis, Ernest G. Butler, Kishore R. Kumar, Kathy H. C. Wu, Susan E. Tomlinson, Stephen Tisch, Abhishek Malhotra, Matthew Lee-Archer, Egor Dolzhenko, Michael A. Eberle, Leslie J. Roberts, Brent L. Fogel, Norbert Bruggemann, Katja Lohmann, Martin B. Delatycki, Melanie Bahlo, Paul J. Lockhart
Summary: This study identified an intronic (GAA) repeat expansion in FGF14 and demonstrated that (GAA)>335 is a disease-causing variant while (GAA)>250 is likely pathogenic. Affected individuals presented with adult-onset cerebellar ataxia with variable features.
AMERICAN JOURNAL OF HUMAN GENETICS
(2023)
Correction
Biochemistry & Molecular Biology
Antony Kaspi, Michael S. Hildebrand, Victoria E. Jackson, Ruth Braden, Olivia van Reyk, Tegan Howell, Simone Debono, Mariana Lauretta, Lottie Morison, Matthew J. Coleman, Richard Webster, David Coman, Himanshu Goel, Mathew Wallis, Gabriel Dabscheck, Lilian Downie, Emma K. Baker, Bronwyn Parry-Fielder, Kirrie Ballard, Eva Harrold, Shaun Ziegenfusz, Mark F. Bennett, Erandee Robertson, Longfei Wang, Amber Boys, Simon E. Fisher, David J. Amor, Ingrid E. Scheffer, Melanie Bahlo, Angela T. Morgan
MOLECULAR PSYCHIATRY
(2023)
Article
Genetics & Heredity
Dongmao Wang, Paul Trevillian, Stephen May, Peter Diakumis, Yanyan Wang, Deb Colville, Melanie Bahlo, Una Greferath, Erica Fletcher, Barbara Young, Heather G. Mack, Judy Savige
Summary: Scalp-Ear-Nipple syndrome, caused by pathogenic KCTD1 variants, is characterized by scalp defect, prominent ears, and rudimentary breasts. This study found further clinical associations in the eye and kidney.
OPHTHALMIC GENETICS
(2023)
Article
Clinical Neurology
Karen L. Oliver, Marina Trivisano, Simone A. Mandelstam, Angela De Dominicis, David I. Francis, Timothy E. Green, Alison M. Muir, Apoorva Chowdhary, Christoph Hertzberg, Klaus Goldhahn, Julia Metreau, Christine Prager, Jason Pinner, Michael Cardamone, Kenneth A. Myers, Richard J. Leventer, Gaetan Lesca, Melanie Bahlo, Michael S. Hildebrand, Heather C. Mefford, Angela M. Kaindl, Nicola Specchio, Ingrid E. Scheffer
Summary: This study analyzed the epileptology and imaging features of WWOX-DEE, and investigated genotype-phenotype correlations, particularly with regard to survival. The results showed that biallelic WWOX pathogenic variants cause an early infantile developmental and epileptic encephalopathy syndrome, with focal seizures and epileptic spasms being the most common seizure types. Patients with two null WWOX pathogenic variants have higher mortality risk.
Letter
Medicine, General & Internal
Melanie Bahlo
MEDICAL JOURNAL OF AUSTRALIA
(2023)
Correction
Multidisciplinary Sciences
Katie L. Ayers, Stefanie Eggers, Ben N. Rollo, Katherine R. Smith, Nadia M. Davidson, Nicole A. Siddall, Liang Zhao, Josephine Bowles, Karin Weiss, Ginevra Zanni, Lydie Burglen, Shay Ben-Shachar, Jenny Rosensaft, Annick Raas-Rothschild, Anne Jorgensen, Ralf B. Schittenhelm, Cheng Huang, Gorjana Robevska, Jocelyn van den Bergen, Franca Casagranda, Justyna Cyza, Svenja Pachernegg, David K. Wright, Melanie Bahlo, Alicia Oshlack, Terrence J. O'Brien, Patrick Kwan, Peter Koopman, Gary R. Hime, Nadine Girard, Chen Hoffmann, Yuval Shilon, Amnon Zung, Enrico Bertini, Mathieu Milh, Bochra Ben Rhouma, Neila Belguith, Anu Bashamboo, Kenneth McElreavey, Ehud Banne, Naomi Weintrob, Bruria BenZeev, Andrew H. Sinclair
NATURE COMMUNICATIONS
(2023)
Article
Endocrinology & Metabolism
Courtney R. Green, Roberto Bonelli, Brendan R. E. Ansell, Simone Tzaridis, Michal K. Handzlik, Grace H. McGregor, Barbara Hart, Jennifer Trombley, Mary M. Reilly, Paul S. Bernstein, Catherine Egan, Marcus Fruttiger, Martina Wallace, Melanie Bahlo, Martin Friedlander, Christian M. Metallo, Marin L. Gantner
Summary: Metabolomic analysis of MacTel, HSAN1, and dual diagnosed patients revealed metabolic distinctions in amino acid and sphingolipid metabolism. MacTel patients exhibited alterations in amino acids resembling diabetes, as well as changes in sphingolipid levels. HSAN1 patients showed abnormal sphingolipid metabolism compared to controls. These findings have implications for further research and therapeutic approaches for these neurodegenerative diseases.
MOLECULAR METABOLISM
(2023)
Article
Multidisciplinary Sciences
Lyndal Henden, Liam G. Fearnley, Natalie Grima, Emily P. McCann, Carol Dobson-Stone, Lauren Fitzpatrick, Kathryn Friend, Lynne Hobson, Sandrine Chan Moi Fat, Dominic B. Rowe, Susan D'Silva, John B. Kwok, Glenda M. Halliday, Matthew C. Kiernan, Srestha Mazumder, Hannah C. Timmins, Margaret Zoing, Roger Pamphlett, Lorel Adams, Melanie Bahlo, Ian P. Blair, Kelly L. Williams
Summary: In this study, we analyzed whole-genome sequencing data from 608 patients with sporadic ALS, 68 patients with sporadic FTD, and 4703 matched controls using three tools. We found that 17.6% of clinically diagnosed ALS and FTD cases had expanded STR alleles reported to be pathogenic or intermediate for other neurodegenerative diseases, providing evidence for their contribution to the development of these diseases. We also identified multiple disease-relevant STR expansions associated with neurodegenerative diseases, highlighting the clinical and pathological pleiotropy of neurodegenerative disease genes and their importance in ALS and FTD.
Article
Immunology
Louis Perriman, Naeimeh Tavakolinia, Sedigheh Jalali, Shuo Li, Peter F. Hickey, Daniela Amann-Zalcenstein, William Wing Ho Ho, Tracey M. Baldwin, Adam T. Piers, Igor E. Konstantinov, Jeremy Anderson, Edouard G. Stanley, Paul V. Licciardi, George Kannourakis, Shalin H. Naik, Hui-Fern Koay, Laura K. Mackay, Stuart P. Berzins, Daniel G. Pellicci
Summary: V?9Vd2 T cells, the largest subset of γδ T cells in adults, play critical roles in immune responses against cancer and infection. Previous studies suggested that these cells mainly develop in the fetal liver and thymus, with little contribution from the postnatal thymus. However, more recent evidence indicates that postnatal thymus may also contribute to the development of these cells. In this study, the researchers used multiple techniques to characterize the development of V?9Vd2 T cells in the postnatal thymus and found three distinct stages of development.
SCIENCE IMMUNOLOGY
(2023)
Article
Hematology
Huimin Cao, Shalin H. Naik, Daniela Amann-Zalcenstein, Peter Hickey, Agus Salim, Benjamin Cao, Susan K. Nilsson, M. Cristina Keightley, Graham J. Lieschke
Summary: This study identifies the crucial role of the ZBTB11 transcription factor in definitive hematopoiesis. Deletion of ZBTB11 in mice leads to embryonic death and hematopoietic failure. Loss of ZBTB11 results in overspecification of hematopoietic stem cells, loss of stemness, impaired differentiation, and cell cycle regulation. This study highlights the cell-intrinsic requirement of ZBTB11 in maintaining a pool of maturation-capable HSCs and progenitor cells.
Review
Biochemistry & Molecular Biology
Haloom Rafehi, Mark F. Bennett, Melanie Bahlo
Summary: Hereditary cerebellar ataxias are a group of progressive neurological disorders caused by repeat expansions. Significant advances have been made in detecting short tandem repeats (STRs) and repeat expansions using whole-genome sequencing data. Established repeat expansion detection pipelines have become a feasible and practical alternative to molecular testing methods, leading to the discovery of many new pathogenic repeat expansions.
EMERGING TOPICS IN LIFE SCIENCES
(2023)
Article
Endocrinology & Metabolism
Roberto Bonelli, Sasha M. Woods, Sarah Lockwood, Paul N. Bishop, Kamron N. Khan, Melanie Bahlo, Brendan R. E. Ansell, Marcus Fruttiger
Summary: The primate retina has specialized regional functions, with the macula being specialized for high acuity vision. Different regions in the retina have different susceptibility to diseases, with the macula being primarily affected.
Article
Medicine, Research & Experimental
Kevin T. Eade, Brendan Robert E. Ansell, Sarah Giles, Regis Fallon, Sarah Harkins-Perry, Takayuki Nagasaki, Simone Tzaridis, Martina Wallace, Elizabeth A. Mills, Samaneh Farashi, Alec Johnson, Lydia Sauer, Barbara Hart, M. Elena Diaz-Rubio, Melanie Bahlo, Christian Metallo, Rando Allikmets, Marin L. Gantner, Paul S. Bernstein, Martin Friedlander
Summary: Patient-derived iPSCs are a powerful tool for studying disease mechanisms, with MacTel iRPE cells showing reduced serine levels and dysregulation of central carbon metabolism. Mitochondrial dysfunction in these cells may represent an alternative disease mechanism beyond the known serine/sphingolipid pathway.
JOURNAL OF CLINICAL INVESTIGATION
(2023)