Article
Genetics & Heredity
Megan Null, Josee Dupuis, Pezhman Sheinidashtegol, Ryan M. Layer, Christopher R. Gignoux, Audrey E. Hendricks
Summary: Identification of rare-variant associations is crucial for understanding the genetic architecture of complex traits and diseases. Existing simulation methods have limitations in using real-variant annotation and accurately estimating the number of rare variants. This study presents a flexible and accurate rare-variant simulation algorithm, RAREsim, that can simulate the expected variant distribution and provide real-variant annotations.
AMERICAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Oncology
Yanhong Liu, Jun Xia, James McKay, Spiridon Tsavachidis, Xiangjun Xiao, Margaret R. Spitz, Chao Cheng, Jinyoung Byun, Wei Hong, Yafang Li, Dakai Zhu, Zhuoyi Song, Susan M. Rosenberg, Michael E. Scheurer, Farrah Kheradmand, Claudio W. Pikielny, Christine M. Lusk, Ann G. Schwartz, Ignacio I. Wistuba, Michael H. Cho, Edwin K. Silverman, Joan Bailey-Wilson, Susan M. Pinney, Marshall Anderson, Elena Kupert, Colette Gaba, Diptasri Mandal, Ming You, Mariza de Andrade, Ping Yang, Triantafillos Liloglou, Michael P. A. Davies, Jolanta Lissowska, Beata Swiatkowska, David Zaridze, Anush Mukeria, Vladimir Janout, Ivana Holcatova, Dana Mates, Jelena Stojsic, Ghislaine Scelo, Paul Brennan, Geoffrey Liu, John K. Field, Rayjean J. Hung, David C. Christiani, Christopher I. Amos
Summary: Recent studies indicate that rare variants could have a significant impact on the etiology of lung cancers. Through comprehensive sequencing, rare deleterious variants associated with lung cancer susceptibility were identified, including both known and novel susceptibility genes. Further mechanistic studies are needed to evaluate the pathogenic effects of these specific alleles.
NPJ PRECISION ONCOLOGY
(2021)
Article
Multidisciplinary Sciences
Sarah Grosche, Ingo Marenholz, Jorge Esparza-Gordillo, Aleix Arnau-Soler, Erola Pairo-Castineira, Franz Rueschendorf, Tarunveer S. Ahluwalia, Catarina Almqvist, Andreas Arnold, Hansjoerg Baurecht, Hans Bisgaard, Klaus Bonnelykke, Sara J. Brown, Mariona Bustamante, John A. Curtin, Adnan Custovic, Shyamali C. Dharmage, Ana Esplugues, Mario Falchi, Dietmar Fernandez-Orth, Manuel A. R. Ferreira, Andre Franke, Sascha Gerdes, Christian Gieger, Hakon Hakonarson, Patrick G. Holt, Georg Homuth, Norbert Hubner, Pirro G. Hysi, Marjo-Riitta Jarvelin, Robert Karlsson, Gerard H. Koppelman, Susanne Lau, Manuel Lutz, Patrik K. E. Magnusson, Guy B. Marks, Martina Mueller-Nurasyid, Markus M. Noethen, Lavinia Paternoster, Craig E. Pennell, Annette Peters, Konrad Rawlik, Colin F. Robertson, Elke Rodriguez, Sylvain Sebert, Angela Simpson, Patrick M. A. Sleiman, Marie Standl, Dora Stoelzl, Konstantin Strauch, Agnieszka Szwajda, Albert Tenesa, Philip J. Thompson, Vilhelmina Ullemar, Alessia Visconti, Judith M. Vonk, Carol A. Wang, Stephan Weidinger, Matthias Wielscher, Catherine L. Worth, Chen-Jian Xu, Young-Ae Lee
Summary: This study identified rare and common variants associated with eczema susceptibility through a meta-analysis, revealing promising therapeutic targets and genetic characteristics of the disease. Rare variants were linked to up-regulation of skin genes while common variants were related to immune cell function.
NATURE COMMUNICATIONS
(2021)
Editorial Material
Multidisciplinary Sciences
Luke M. M. Evans, Pamela N. Romero N. Villela
Summary: An analysis of rare genetic variants shows their impact on human traits is mediated through similar biological pathways as common variants, enhancing our understanding of their influence on complex traits.
Article
Multidisciplinary Sciences
Andrew D. Paterson, Sang-Cheol Seok, Veronica J. Vieland
Summary: Next-generation sequencing has revolutionized genetic discoveries for rare diseases. However, most identified variants are rare and found in small pedigrees, posing challenges for estimating penetrance and providing genetic counseling.
Article
Multidisciplinary Sciences
Yunfeng Huang, Dora Bodnar, Chia-Yen Chen, Gabriela Sanchez-Andrade, Mark Sanderson, Jun E. Shi, Katherine S. Meilleur, Matthew A. Hurles, Sebastian Gerety, Ellen Tsai, Heiko Runz
Summary: The authors conducted an exome study on hand grip strength, which serves as a proxy for overall muscle strength. They discovered six significant genes, associated with diseases, and found that rare and common genetic variants both contribute to muscle strength. Muscle strength has a strong genetic basis and is a predictor of various negative health outcomes, including mortality.
NATURE COMMUNICATIONS
(2023)
Review
Genetics & Heredity
Haipeng Pang, Ying Xia, Shuoming Luo, Gan Huang, Xia Li, Zhiguo Xie, Zhiguang Zhou
Summary: Type 1 diabetes mellitus (T1DM) is an autoimmune disorder with a complex and heterogeneous nature, caused by a combination of genetic susceptibility and environmental factors. While known susceptibility loci can explain a significant portion of the heritability of T1DM, undetected rare and low-frequency variants may account for some of its missing genetic components. Rare and low-frequency variants are believed to have larger effect sizes and play more significant roles in susceptibility to common diseases like T1DM compared to common variants.
JOURNAL OF MEDICAL GENETICS
(2021)
Article
Gastroenterology & Hepatology
Satoshi Tamaoka, Akinari Fukuda, Kazuhiko Nakabayashi, Keiko Matsubara, Hiroko Ogata-Kawata, Yuki Muranishi, Kenichiro Hata, Yuko Kato-Fukui, Seisuke Sakamoto, Mureo Kasahara, Maki Fukami
Summary: In this study, genome-wide screening was performed on 15 Japanese patients with non-syndromic biliary atresia (BA) and 509 control individuals. The results show that rare damaging variants in MFHAS1 may be a risk factor for non-syndromic BA.
HEPATOLOGY RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Tianyi Wang, Wenchuang He, Xiaoxia Li, Chao Zhang, Huiying He, Qiaoling Yuan, Bin Zhang, Hong Zhang, Yue Leng, Hua Wei, Qiang Xu, Chuanlin Shi, Xiangpei Liu, Mingliang Guo, Xianmeng Wang, Wu Chen, Zhipeng Zhang, Longbo Yang, Yang Lv, Hongge Qian, Bintao Zhang, Xiaoman Yu, Congcong Liu, Xinglan Cao, Yan Cui, Qianqian Zhang, Xiaofan Dai, Longbiao Guo, Yuexing Wang, Yongfeng Zhou, Jue Ruan, Qian Qian, Lianguang Shang
Summary: Detailed analysis of a large rice population revealed the genetic variations and their frequency in different subsets of the population. The results indicated that most of the obtained variants were rare and difficult to detect in small populations. The study provides a rich genetic basis for understanding natural rice variations and a powerful tool for future rice research.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Jaeyong Choi, Sungjae Kim, Juhyun Kim, Ho-Young Son, Seong-Keun Yoo, Chang-Uk Kim, Young Jun Park, Sungji Moon, Bukyoung Cha, Min Chul Jeon, Kyunghyuk Park, Jae Moon Yun, Belong Cho, Namcheol Kim, Changhoon Kim, Nak-Jung Kwon, Young Joo Park, Fumihiko Matsuda, Yukihide Momozawa, Michiaki Kubo, Hyun-Jin Kim, Jin-Ho Park, Jeong-Sun Seo, Jong-Il Kim, Sun-Wha Im
Summary: In order to advance global precision medicine, we created a reference panel consisting of over 11,000 Asian individuals. Using this panel, we discovered 39 previously unidentified associations, with over half of the variants being specific to East Asian populations. We also found genes related to traits such as height and body mass index, as well as putative regulatory mechanisms for rare noncoding variants with cell type-specific effects.
Article
Biochemistry & Molecular Biology
Dmitri S. Pavlichin, HoJoon Lee, Stephanie U. Greer, Susan M. Grimes, Tsachy Weissman, Hanlee P. Ji
Summary: K-mers are short DNA sequences used for genome sequence analysis. The computational requirements for analyzing K-mer information on a large scale can be enormous. KmerKeys addresses this challenge by developing a new indexing data structure and providing fast query speeds and cloud computation capabilities.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Genetics & Heredity
David Curtis
Summary: Rare variants in genes, particularly on the X chromosome, have been found to have major effects on lipid levels. The study demonstrated the importance of including principal components and sex as covariates in genetic analysis, and identified significant associations with genes like LDLR and PCSK9. Variants classified as deleterious by SIFT were found to have a twofold effect and are present in approximately 1.5% of the population, highlighting their impact on hyperlipidaemia risk.
JOURNAL OF MEDICAL GENETICS
(2022)
Article
Genetics & Heredity
Riccardo Sangermano, Iris Deitch, Virginie G. Peter, Rola Ba-Abbad, Emily M. Place, Erin Zampaglione, Naomi E. Wagner, Anne B. Fulton, Luisa Coutinho-Santos, Boris Rosin, Vincent Dunet, Ala'a AlTalbishi, Eyal Banin, Ana Berta Sousa, Mariana Neves, Anna Larson, Mathieu Quinodoz, Michel Michaelides, Tamar Ben-Yosef, Eric A. Pierce, Carlo Rivolta, Andrew R. Webster, Gavin Arno, Dror Sharon, Rachel M. Huckfeldt, Kinga M. Bujakowska
Summary: The study validates the association between INPP5E gene mutations and non-syndromic IRD, as well as the wide phenotypic spectrum, demonstrating the involvement of genetic modifiers. Additionally, the research identifies 12 rare INPP5E variants not previously reported.
NPJ GENOMIC MEDICINE
(2021)
Article
Oncology
Rong Bu, Abdul K. Siraj, Saud Azam, Kaleem Iqbal, Zeeshan Qadri, Maha Al-Rasheed, Saif S. Al-Sobhi, Fouad Al-Dayel, Khawla S. Al-Kuraya
Summary: This study identified a strong association between GALNT9 gene and rare inactivating variants in Middle Eastern population with Papillary thyroid carcinoma (PTC), and also found several other genes associated with PTC risk. The study highlights the potential role of GALNT9 and other genes in PTC predisposition and emphasizes the need for large collaborations and innovative approaches to understand the genetic heterogeneity of PTC predisposition.
Article
Medicine, General & Internal
Jan-Bernd Funcke, Barbara Moepps, Julian Roos, Julia von Schnurbein, Kenneth Verstraete, Elke Froehlich-Reiterer, Katja Kohlsdorf, Adriana Nunziata, Stephanie Brandt, Alexandra Tsirigotaki, Ann Dansercoer, Elisabeth Suppan, Basma Haris, Klaus-Michael Debatin, Savvas N. Savvides, I. Sadaf Farooqi, Khalid Hussain, Peter Gierschik, Pamela Fischer-Posovszky, Martin Wabitsch
Summary: This article describes two novel homozygous leptin variants that caused intense hyperphagia, severe obesity, and high leptin levels in two unrelated children. These variants bind to the leptin receptor but have marginal signaling. In the presence of nonvariant leptin, they act as competitive antagonists. High-dose recombinant leptin treatment was initiated and gradually reduced, resulting in near-normal weight for both patients. Antidrug antibodies developed in the patients, but did not appear to affect efficacy. No severe adverse events were observed.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Infectious Diseases
Yuling Li, Yubing Hu, Yan Zhao, Qinghui Wang, Huguette Gaelle Ngassa Mbenda, Veerayuth Kittichai, Saranath Lawpoolsri, Jetsumon Sattabongkot, Lynette Menezes, Xiaoming Liu, Liwang Cui, Yaming Cao
Article
Biochemistry & Molecular Biology
Xiaoming Liu
MOLECULAR BIOLOGY AND EVOLUTION
(2020)
Article
Biochemical Research Methods
Yongsheng Bai, Steve Baker, Kevin Exoo, Xingqin Dai, Lizhong Ding, Naureen Aslam Khattak, Hongtao Li, Hannah Liu, Xiaoming Liu
BMC BIOINFORMATICS
(2020)
Article
Multidisciplinary Sciences
Cheng Xue, Navin Rustagi, Xiaoming Liu, Muthuswamy Raveendran, R. Alan Harris, Manjunath Gorentla Venkata, Jeffrey Rogers, Fuli Yu
Article
Health Care Sciences & Services
Xiaoming Liu, Deborah Cragun, Jinyong Pang, Swamy R. Adapa, Renee Fonseca, Rays H. Y. Jiang
JOURNAL OF PERSONALIZED MEDICINE
(2020)
Article
Genetics & Heredity
Xiaoming Liu, Chang Li, Chengcheng Mou, Yibo Dong, Yicheng Tu
Article
Medicine, General & Internal
Bridget M. Lin, Kelsey E. Grinde, Jennifer A. Brody, Charles E. Breeze, Laura M. Raffield, Josyf C. Mychaleckyj, Timothy A. Thornton, James A. Perry, Leslie J. Baier, Lisa de las Fuentes, Xiuqing Guo, Benjamin D. Heavner, Robert L. Hanson, Yi-Jen Hung, Huijun Qian, Chao A. Hsiung, Shih-Jen Hwang, Margaret R. Irvin, Deepti Jain, Tanika N. Kelly, Sayuko Kobes, Leslie Lange, James P. Lash, Yun Li, Xiaoming Liu, Xuenan Mi, Solomon K. Musani, George J. Papanicolaou, Afshin Parsa, Alex P. Reiner, Shabnam Salimi, Wayne H-H Sheu, Alan R. Shuldiner, Kent D. Taylor, Albert Smith, Jennifer A. Smith, Adrienne Tin, Dhananjay Vaidya, Robert B. Wallace, Kenichi Yamamoto, Saori Sakaue, Koichi Matsuda, Yoichiro Kamatani, Yukihide Momozawa, Lisa R. Yanek, Betsi A. Young, Wei Zhao, Yukinori Okada, Gonzalo Abecasis, Bruce M. Psaty, Donna K. Arnett, Eric Boerwinkle, Jianwen Cai, Ida Yii-Der Chen, Adolfo Correa, L. Adrienne Cupples, Jiang He, Sharon Lr Kardia, Charles Kooperberg, Rasika A. Mathias, Braxton D. Mitchell, Deborah A. Nickerson, Steve T. Turner, Ramachandran S. Vasan, Jerome Rotter, Daniel Levy, Holly J. Kramer, Anna Kottgen, Stephen S. Rich, Dan-Yu Lin, Sharon R. Browning, Nora Franceschini
Summary: This study utilized WGS data from multi-ethnic studies to identify novel loci influencing kidney traits, with some driven by low frequency variants more commonly observed in non-European ancestries. Additionally, the study replicated two known loci, and applied statistical approaches to detect aggregated variants and ancestry-specific variants.
Article
Biology
Ardalan Naseri, Kecong Tang, Xin Geng, Junjie Shi, Jing Zhang, Pramesh Shakya, Xiaoming Liu, Shaojie Zhang, Degui Zhi
Summary: This study conducted an individual-centric analysis of IBD segments among the UK Biobank participants, revealing genetic makeup, personal genealogical history, and social behavior characteristics of individuals with important genetic connections at the population scale, opening possibilities for further studies of individual's genetic connections in biobank data.
Review
Biochemical Research Methods
Yibo Dong, Chang Li, Kami Kim, Liwang Cui, Xiaoming Liu
Summary: Humans have coexisted with pathogenic microorganisms and genome annotation of these microorganisms has become a challenging task. This paper summarizes the methods and tools for genome annotation of pathogenic microorganisms, conducts real-world comparisons, and discusses current challenges and issues.
BRIEFINGS IN BIOINFORMATICS
(2021)
Article
Multidisciplinary Sciences
Daniel Taliun, Daniel N. Harris, Michael D. Kessler, Jedidiah Carlson, Zachary A. Szpiech, Raul Torres, Sarah A. Gagliano Taliun, Andre Corvelo, Stephanie M. Gogarten, Hyun Min Kang, Achilleas N. Pitsillides, Jonathon LeFaive, Seung-been Lee, Xiaowen Tian, Brian L. Browning, Sayantan Das, Anne-Katrin Emde, Wayne E. Clarke, Douglas P. Loesch, Amol C. Shetty, Thomas W. Blackwell, Albert Smith, Quenna Wong, Xiaoming Liu, Matthew P. Conomos, Dean M. Bobo, Francois Aguet, Christine Albert, Alvaro Alonso, Kristin G. Ardlie, Dan E. Arking, Stella Aslibekyan, Paul L. Auer, John Barnard, R. Graham Barr, Lucas Barwick, Lewis C. Becker, Rebecca L. Beer, Emelia J. Benjamin, Lawrence F. Bielak, John Blangero, Michael Boehnke, Donald W. Bowden, Jennifer A. Brody, Esteban G. Burchard, Brian E. Cade, James F. Casella, Brandon Chalazan, Daniel Chasman, Yii-Der Ida Chen, Michael H. Cho, Seung Hoan Choi, Mina K. Chung, Clary B. Clish, Adolfo Correa, Joanne E. Curran, Brian Custer, Dawood Darbar, Michelle Daya, Mariza de Andrade, Dawn L. DeMeo, Susan K. Dutcher, Patrick T. Ellinor, Leslie S. Emery, Celeste Eng, Diane Fatkin, Tasha Fingerlin, Lukas Forer, Myriam Fornage, Nora Franceschini, Christian Fuchsberger, Stephanie M. Fullerton, Soren Germer, Mark T. Gladwin, Daniel J. Gottlieb, Xiuqing Guo, Michael E. Hall, Jiang He, Nancy L. Heard-Costa, Susan R. Heckbert, Marguerite R. Irvin, Jill M. Johnsen, Andrew D. Johnson, Robert Kaplan, Sharon L. R. Kardia, Tanika Kelly, Shannon Kelly, Eimear E. Kenny, Douglas P. Kiel, Robert Klemmer, Barbara A. Konkle, Charles Kooperberg, Anna Kottgen, Leslie A. Lange, Jessica Lasky-Su, Daniel Levy, Xihong Lin, Keng-Han Lin, Chunyu Liu, Ruth J. F. Loos, Lori Garman, Robert Gerszten, Steven A. Lubitz, Kathryn L. Lunetta, Angel C. Y. Mak, Ani Manichaikul, Alisa K. Manning, Rasika A. Mathias, David D. McManus, Stephen T. McGarvey, James B. Meigs, Deborah A. Meyers, Julie L. Mikulla, Mollie A. Minear, Braxton D. Mitchell, Sanghamitra Mohanty, May E. Montasser, Courtney Montgomery, Alanna C. Morrison, Joanne M. Murabito, Andrea Natale, Pradeep Natarajan, Sarah C. Nelson, Kari E. North, Jeffrey R. O'Connell, Nicholette D. Palmer, Nathan Pankratz, Gina M. Peloso, Patricia A. Peyser, Jacob Pleiness, Wendy S. Post, Bruce M. Psaty, D. C. Rao, Susan Redline, Alexander P. Reiner, Dan Roden, Jerome Rotter, Ingo Ruczinski, Chloe Sarnowski, Sebastian Schoenherr, David A. Schwartz, Jeong-Sun Seo, Sudha Seshadri, Vivien A. Sheehan, Wayne H. Sheu, M. Benjamin Shoemaker, Nicholas L. Smith, Jennifer A. Smith, Nona Sotoodehnia, Adrienne M. Stilp, Weihong Tang, Kent D. Taylor, Marilyn Telen, Timothy A. Thornton, Russell P. Tracy, David J. Van den Berg, Ramachandran S. Vasan, Karine A. Viaud-Martinez, Scott Vrieze, Daniel E. Weeks, Bruce S. Weir, Scott T. Weiss, Lu-Chen Weng, Cristen J. Willer, Yingze Zhang, Xutong Zhao, Donna K. Arnett, Allison E. Ashley-Koch, Kathleen C. Barnes, Eric Boerwinkle, Stacey Gabriel, Richard Gibbs, Kenneth M. Rice, Stephen S. Rich, Edwin K. Silverman, Pankaj Qasba, Weiniu Gan, George J. Papanicolaou, Deborah A. Nickerson, Sharon R. Browning, Michael C. Zody, Sebastian Zollner, James G. Wilson, L. Adrienne Cupples, Cathy C. Laurie, Cashell E. Jaquish, Ryan D. Hernandez, Timothy D. O'Connor, Goncalo R. Abecasis
Summary: The TOPMed program aims to study the genetic architecture and biology of heart, lung, blood, and sleep disorders to improve diagnosis, treatment, and prevention of these diseases. Resources include a variant browser, genotype imputation server, and genomic and phenotypic data available through dbGaP. The study detected a large number of rare genetic variants, providing insights into mutation processes and recent human evolutionary history.
Article
Cell Biology
Chang Li, Aurora Wu, Kevin Song, Jeslyn Gao, Eric Huang, Yongsheng Bai, Xiaoming Liu
Summary: This study explores the causal effects of miRNAs on the severity of COVID-19, identifying two high-confidence miRNAs that may have causal effects on developing severe cases of COVID-19. By utilizing miRNA eQTL data, potential miRNA biomarkers are identified to assist in better and earlier diagnoses and risk assessments of severe COVID-19 cases.
Article
Genetics & Heredity
Chang Li, Degui Zhi, Kai Wang, Xiaoming Liu
Summary: This study developed pathogenicity prediction models, MetaRNN and MetaRNN-indel, using context annotations and deep learning methods to improve the identification and prioritization of rare harmful genetic variants. These models outperform state-of-the-art competitors and achieve a more interpretable score distribution, making them suitable for integrated genotype-phenotype association analysis methods.
Article
Anthropology
Jinyong Pang, Xiaoming Liu
Summary: Biological anthropologists often analyze incomplete bioarcheological or forensic skeleton specimens. This study evaluated the performance of popular statistical methods for imputing missing metric measurements using two datasets. Multiple imputation methods outperformed single imputation methods, and Bayesian linear regression, EM with Bootstrapping, PMM, and derivative linear regression models in mice performed well in terms of accuracy, robustness, and speed. Based on these findings, a practical procedure for choosing appropriate imputation methods is suggested.
AMERICAN JOURNAL OF BIOLOGICAL ANTHROPOLOGY
(2023)
Article
Anthropology
Jinyong Pang, Yibo Dong, Christopher Turner, Chang Li, Xiaoming Liu
Summary: Howells' craniometric data set, the largest publicly available data set on the internet, has been widely used for craniometric methods development. The study reveals data inconsistency between the main and test data sets, with missing decimal points likely causing the abnormality.
AMERICAN JOURNAL OF BIOLOGICAL ANTHROPOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Xiaoming Liu, Yun-Xin Fu