Article
Multidisciplinary Sciences
Matteo Sesia, Stephen Bates, Emmanuel Candes, Jonathan Marchini, Chiara Sabatti
Summary: The study introduces a comprehensive statistical framework for analyzing data from genome-wide association studies of polygenic traits, demonstrating validity and effectiveness through simulations and applications to the UK Biobank data. The method outperforms state-of-the-art alternatives and is supported by comparisons with other studies, offering researchers fast software for analyzing Biobank-scale datasets.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Obstetrics & Gynecology
Che Xu, Xiangyan Ruan, Alfred O. Mueck
Summary: Menopause not only marks the end of reproductive life, but also has associations with diseases like hyperlipidemia, atherosclerotic cardiovascular disease, osteoporosis, and breast cancer. Traditional epidemiological studies have shown that heredity plays a significant role in determining the age of natural menopause (ANM). Advances in genomic technology have enabled researchers to conduct genome-wide association studies, revealing that defects in DNA damage repair pathways are the primary genetic mechanism. Further genetic and epidemiological studies, including research on polygenic scores and genetic mechanisms, are needed to investigate the pathogenesis and mechanisms related to menopause and its associated diseases.
REPRODUCTIVE BIOMEDICINE ONLINE
(2023)
Article
Multidisciplinary Sciences
Han-Ming Liu, Jin-Ping Zheng, Dan Yang, Zhao-Fa Liu, Zi Li, Zhen-Zhen Hu, Ze-Nan Li
Summary: The study indicates that a recessive/dominant model may be more effective than the additive model in case-control-based genome-wide association studies. Through experiments, it was shown that the recessive model has better accuracy and area under the curve compared to the additive model, suggesting a new direction for research.
Article
Computer Science, Interdisciplinary Applications
Xinyue Wang, Xiaoqian Jiang, Jaideep Vaidya
Summary: The paper proposes two algorithms for generating synthetic SNPs that are indistinguishable from real SNPs. Through game theoretic analysis, it demonstrates the possibility of incentivizing honest behavior by the server. Extensive experiments show that the proposed method can ensure efficient and trustworthy outsourcing of logistic regression for GWAS.
JOURNAL OF BIOMEDICAL INFORMATICS
(2021)
Article
Biochemical Research Methods
Yongwen Zhuang, Brooke N. Wolford, Kisung Nam, Wenjian Bi, Wei Zhou, Cristen J. Willer, Bhramar Mukherjee, Seunggeun Lee
Summary: A new method for genetic association test with family disease history is proposed, which can control the problems caused by increased phenotype correlation and case-control imbalance, and has better performance in detecting variant-phenotype associations.
Article
Multidisciplinary Sciences
Xiaoyu Liang, Xuewei Cao, Qiuying Sha, Shuanglin Zhang
Summary: The article introduces a novel multivariate method for phenome-wide association studies (PheWAS) and demonstrates its superiority through extensive simulation studies and real-life application. The proposed method involves hierarchical clustering, clustering linear combination, and false discovery rate control steps.
Review
Plant Sciences
Laura Tibbs Cortes, Zhiwu Zhang, Jianming Yu
Summary: Genome-wide association studies (GWAS) have become a powerful tool for investigating complex traits, with the development of the mixed model framework reducing false positives. Advances in technology have led to the development of methods to increase computational speed or improve statistical power in GWAS.
Article
Multidisciplinary Sciences
Ludivine Obry, Cyril Dalmasso
Summary: In this study, we evaluated recent weighted multiple testing procedures for genome wide association studies (GWAS) through a simulation study. We also introduced a new efficient procedure called wBHa, which prioritizes the detection of genetic variants with low minor allel frequencies while maximizing overall detection power. Our results demonstrated that wBHa outperformed other procedures in detecting rare variants while maintaining good overall power.
Review
Biochemistry & Molecular Biology
Imane Lalami, Carole Abo, Bruno Borghese, Charles Chapron, Daniel Vaiman
Summary: This review discusses the genetics of endometriosis, a common feminine disease with a genetic heritability estimated at around 50%. Large GWAS studies have identified some genes and loci associated with the disease, but a significant portion of the heritability remains unexplained. Additional efforts such as exome sequencing may be needed to fully elucidate the genetic factors of endometriosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Editorial Material
Medicine, General & Internal
Lisa Bastarache, Joshua C. Denny, Dan M. Roden
Summary: This article discusses the concept and methodology of phenome-wide association studies, which aim to identify associations between genetic variations and phenotypic traits using a dataset.
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
(2022)
Article
Genetics & Heredity
Ekaterina Orlova, Tom Dudding, Jonathan M. Chernus, Rasha N. Alotaibi, Simon Haworth, Richard J. Crout, Myoung Keun Lee, Nandita Mukhopadhyay, Eleanor Feingold, Steven M. Levy, Daniel W. McNeil, Betsy Foxman, Robert J. Weyant, Nicholas J. Timpson, Mary L. Marazita, John R. Shaffer
Summary: Although genetics plays a role in early childhood caries (ECC) risk, little is known about the specific genetic determinants. This study conducted genome-wide association studies (GWAS) and transcriptome-wide association studies (TWAS) to identify genes associated with ECC. The results indicated suggestive evidence for the involvement of certain genetic regions and revealed four risk genes, including TAS2R14 which is associated with innate immunity and antimicrobial defense against cariogenic bacteria. These findings provide insights into the genetic architecture of ECC and highlight the importance of host-microbial interaction in caries risk.
Article
Multidisciplinary Sciences
Abbas Saad Alatrany, Wasiq Khan, Abir Hussain, Dhiya Al-Jumeily
Summary: The increasing incidence of Alzheimer's disease (AD) poses socioeconomic challenges. In this study, a hybrid feature selection approach and neural network models are used to predict AD. The approach outperformed existing methods with 99% accuracy and f1-score, providing impactful outcomes for other chronic diseases.
Review
Genetics & Heredity
Lijuan Wang, Xiaomeng Zhang, Xiangrui Meng, Fotios Koskeridis, Andrea Georgiou, Lili Yu, Harry Campbell, Evropi Theodoratou, Xue Li
Summary: Phenome-wide association study (PheWAS) has been increasingly used to identify novel genetic associations across a wide spectrum of phenotypes. This systematic review provides a comprehensive overview of PheWAS methodology, discussing its advantages and challenges, and offering potential implications for future studies. The majority of PheWAS studies included over 10,000 participants, defined phenotypes based on electronic medical records data, used genetic variants as predictors, and conducted replication analysis to validate findings.
JOURNAL OF MEDICAL GENETICS
(2021)
Article
Multidisciplinary Sciences
Jack W. O'Sullivan, John P. A. Ioannidis
Summary: This study compared SNVs from earlier and later GWAS and found a replication rate of 85.0% in subsequent studies, with a lower replication rate for binary phenotypes compared to quantitative phenotypes. The study also identified a decrease in SNV effect size for binary phenotypes, but an increase for quantitative phenotypes, and developed a model that could predict SNV replication effectively.
SCIENTIFIC REPORTS
(2021)
Article
Psychiatry
Nora Strom, Dirk J. A. Smit, Talisa Silzer, Conrad Iyegbe, Christie L. Burton, Rene Pool, Mathieu Lemire, James J. Crowley, Jouke-Jan Hottenga, Volen Z. Ivanov, Henrik Larsson, Paul Lichtenstein, Patrik Magnusson, Christian Ruck, Russell J. Schachar, Hei Man Wu, Sandra M. Meier, Jennifer Crosbie, Paul D. Arnold, Manuel Mattheisen, Dorret Boomsma, David Mataix-Cols, Danielle Cath
Summary: This study reveals the heritability of hoarding symptoms and identifies genetic associations with schizophrenia, autism spectrum disorder, and educational attainment. However, no significant loci were detected in the genome-wide analysis.
TRANSLATIONAL PSYCHIATRY
(2022)
Editorial Material
Medicine, General & Internal
Logan G. Spector, Christopher L. Moertel, H. Irene Su
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
(2022)
Article
Oncology
Thomas P. Ahern, Logan G. Spector, Per Damkier, Buket Ozturk Esen, Sinna P. Ulrichsen, Katrine Eriksen, Timothy L. Lash, Henrik Toft Sorensen, Deirdre P. Cronin-Fenton
Summary: The exposure to phthalates during childhood is associated with osteosarcoma and lymphoma before the age of 19. This association is particularly strong for low-molecular phthalates.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2022)
Article
Biochemistry & Molecular Biology
Nathan Pankratz, Peng Wei, Jennifer A. Brody, Ming-Huei Chen, Paul S. Vries, Jennifer E. Huffman, Mary Rachel Stimson, Paul L. Auer, Eric Boerwinkle, Mary Cushman, Moniek P. M. Maat, Aaron R. Folsom, Oscar H. Franco, Richard A. Gibbs, Kelly K. Haagenson, Albert Hofman, Jill M. Johnsen, Christie L. Kovar, Robert Kraaij, Barbara McKnight, Ginger A. Metcalf, Donna Muzny, Bruce M. Psaty, Weihong Tang, Andre G. Uitterlinden, Jeroen G. J. Rooij, Abbas Dehghan, Christopher J. O'Donnell, Alex P. Reiner, Alanna C. Morrison, Nicholas L. Smith
Summary: Through whole-exome sequencing in a large cohort of individuals of European and African American ancestry, rare variants associated with fibrinogen, coagulation factors VII and VIII, and von Willebrand factor were identified. These new variants were independent of known common variants and tended to have larger effect sizes, with some variants also being associated with increased risk of venous thromboembolism.
HUMAN MOLECULAR GENETICS
(2022)
Article
Oncology
Freddy A. Barragan, Lauren J. Mills, Andrew R. Raduski, Erin L. Marcotte, Kelsey E. Grinde, Logan G. Spector, Lindsay A. Williams
Summary: Black children have lower incidence yet worse survival in B-cell acute lymphoblastic leukemia (B-ALL). Genetic ancestry and differentially expressed genes associated with ancestry play a role in death risk. The impact of reported race/ethnicity on death risk varies after adjusting for genetic ancestry genes. Other factors also contribute to B-ALL survival.
Article
Economics
Martha J. Bailey, Susan H. Leonard, Joseph Price, Evan Roberts, Logan Spector, Mengying Zhang
Summary: This paper describes the digitization of almost 185,000 causes of death for Ohio by combining handwriting recognition, data cleaning algorithms, and semi-automated classification of causes. The methods used in this research can be applied to other collections of handwritten data.
EXPLORATIONS IN ECONOMIC HISTORY
(2023)
Article
Hematology
Brian T. Steffen, James S. Pankow, Faye L. Norby, Pamela L. Lutsey, Ryan T. Demmer, Weihua Guan, Nathan Pankratz, Aixin Li, Guning Liu, Kunihiro Matsushita, Adrienne Tin, Weihong Tang
Summary: This study identified proteomic signatures and pathways related to 23 gene loci associated with abdominal aortic aneurysm (AAA). The results suggest that low levels of neogenin and kit ligand may be novel risk factors for AAA development.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2023)
Article
Medicine, General & Internal
Jennifer M. Geris, Mark R. Schleiss, Anthony J. Hooten, Erica Langer, Nelmary Hernandez-Alvarado, Michelle A. Roesler, Jeannette Sample, Lindsay A. Williams, David S. Dickens, Rajen J. Mody, Yaddanapudi Ravindranath, Kate L. Gowans, Matthew G. Pridgeon, Logan G. Spector, Heather H. Nelson
Summary: Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer and a leading cause of death in children. Congenital cytomegalovirus (cCMV) has been identified as a potential risk factor for ALL. This study compared the prevalence of cCMV infection between ALL cases and matched controls, and found that cCMV was associated with increased risk of hyperdiploid ALL.
Article
Cardiac & Cardiovascular Systems
Rachel Zmora, Logan Spector, John Bass, Amanda Thomas, Jessica Knight, Kamakshi Lakshminarayan, James St Louis, Lazaros Kochilas
Summary: The study found that procedure-specific center volume is inversely associated with early postoperative mortality for infantile congenital heart surgery (CHS) but has no measurable effect on later mortality.
ANNALS OF THORACIC SURGERY
(2023)
Article
Oncology
Shuo Wang, Guillaume C. Onyeaghala, Nathan Pankratz, Heather H. Nelson, Bharat Thyagarajan, Weihong Tang, Faye L. Norby, Chinenye Ugoji, Corinne E. Joshu, Christian R. Gomez, David J. Couper, Josef Coresh, Elizabeth A. Platz, Anna E. Prizment
Summary: The study found that MICA and MICB are associated with colorectal cancer development, and low sMICA levels are related to lower risk of colorectal cancer. These findings highlight the importance of immune surveillance in colorectal cancer.
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2023)
Article
Endocrinology & Metabolism
Matthew H. Nguyen, Wei Zhang, Nathan Pankratz, John Lane, Prashant Chitiboina, Fabio R. Faucz, James L. Mills, Constantine A. Stratakis, Christina Tatsi
Summary: In this exploratory study, we did not identify any significant genetic variants associated with the recovery time of hypothalamic-pituitary-adrenal (HPA) axis in patients with endogenous Cushing disease (CD) after remission. Although the BAG1 gene showed correlation with shorter duration of postsurgical adrenal insufficiency (AI), patients with BAG1 variants later experienced recurrence.
JOURNAL OF THE ENDOCRINE SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Shannon M. Sullivan, Ben Cole, John Lane, John J. Meredith, Erica Langer, Anthony J. Hooten, Michelle Roesler, Kathy L. McGraw, Nathan Pankratz, Jenny N. Poynter
Summary: Maintenance of telomere length is believed to be crucially involved in cancer biology, especially in myeloid malignancies. Using polygenic risk score and Mendelian randomization analyses, this study demonstrates a significant association between genetically predicted leukocyte telomere length (LTL) and acute myeloid leukemia (AML) risk, but not myelodysplastic syndrome (MDS) risk. The findings suggest that genetic variation in telomere-related genes may be important in the development of AML, highlighting the potential significance of telomere function and maintenance in AML etiology.
HUMAN MOLECULAR GENETICS
(2023)
Article
Oncology
Philip J. Lupo, Tiffany M. Chambers, Beth A. Mueller, Jacqueline Clavel, John D. Dockerty, David R. Doody, Friederike Erdmann, Sameera Ezzat, Tommaso Filippini, Johnni Hansen, Julia E. Heck, Claire Infante-Rivard, Alice Y. Kang, Corrado Magnani, Carlotta Malagoli, Catherine Metayer, Helen D. Bailey, Ana M. Mora, Evangelia Ntzani, Eleni Th Petridou, Maria S. Pombo-de-Oliveira, Wafaa M. Rashed, Eve Roman, Joachim Schuz, Catharina Wesseling, Logan G. Spector, Michael E. Scheurer
Summary: The study explores the associations between nonchromosomal birth defects and childhood leukemia using data from the Childhood Cancer and Leukemia International Consortium. The results suggest possible novel genetic and environmental factors associated with birth defects that may also increase leukemia susceptibility.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Oncology
Cindy Im, Noha Sharafeldin, Yan Yuan, Zhaoming Wang, Yadav Sapkota, Zhanni Lu, Logan G. Spector, Rebecca M. Howell, Michael A. Arnold, Melissa M. Hudson, Kirsten K. Ness, Leslie L. Robison, Smita Bhatia, Gregory T. Armstrong, Joseph P. Neglia, Yutaka Yasui, Lucie M. Turcotte
Summary: This study evaluated SMNs among long-term childhood cancer survivors of European and African genetic ancestry, finding that a polygenic risk score (PRS) could significantly impact SMN risk in survivors who did not receive radiation therapy and were treated with specific chemotherapies.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Yun Soo Hong, Stephanie L. Battle, Wen Shi, Daniela Puiu, Vamsee Pillalamarri, Jiaqi Xie, Nathan Pankratz, Nicole J. Lake, Monkol Lek, Jerome I. Rotter, Stephen S. Rich, Charles Kooperberg, Alex P. Reiner, Paul L. Auer, Nancy Heard-Costa, Chunyu Liu, Meng Lai, Joanne M. Murabito, Daniel Levy, Megan L. Grove, Alvaro Alonso, Richard Gibbs, Shannon Dugan-Perez, Lukasz P. Gondek, Eliseo Guallar, Dan E. Arking
Summary: Based on the study of participants in the UK Biobank, it was found that mitochondrial heteroplasmy is associated with increased risk of all-cause mortality and the prevalence and incidence of cancer, especially leukemia.
NATURE COMMUNICATIONS
(2023)
Article
Genetics & Heredity
Vamsee Pillalamarri, Wen Shi, Conrad Say, Stephanie Yang, John Lane, Eliseo Guallar, Nathan Pankratz, Dan E. Arking
Summary: Inter-individual variation in mtDNA copy number, which reflects mitochondrial function and is associated with aging-related diseases, was examined in the exomes of White ancestry individuals. Rare variants in several genes, including known mtDNA depletion syndrome genes and a tyrosine kinase mutation, were found to be associated with mtDNA-CN. Novel genes involved in mitochondrial proteome quality and hematopoiesis were also identified. These findings suggest that strong-effect mutations in the nuclear genome contribute to the genetic architecture of mtDNA-CN.
HUMAN GENETICS AND GENOMICS ADVANCES
(2023)
