Article
Genetics & Heredity
Nathan LaPierre, Kodi Taraszka, Helen Huang, Rosemary He, Farhad Hormozdiari, Eleazar Eskin
Summary: As GWAS continue to grow in size, the need for fine mapping methods becomes increasingly important. MsCAVIAR is a novel approach that can identify causal variants in associated regions across multiple studies, accurately describing the potential for different SNP effect sizes in various populations.
Article
Genetics & Heredity
Zeyun Lu, Shyamalika Gopalan, Dong Yuan, David Conti, Bogdan Pasaniuc, Alexander Gusev, Nicholas Mancuso
Summary: Transcriptome-wide association studies (TWASs) are a powerful approach to identify genes associated with complex diseases. This study introduces a multi-ancestry framework called MA-FOCUS for improved gene identification. Results show that MA-FOCUS outperforms single-ancestry methods in gene identification.
AMERICAN JOURNAL OF HUMAN GENETICS
(2022)
Review
Agronomy
Dinesh K. Saini, Yuvraj Chopra, Jagmohan Singh, Karansher S. Sandhu, Anand Kumar, Sumandeep Bazzer, Puja Srivastava
Summary: This review provides a comprehensive overview of the importance of GWAS in wheat, including population design, high-throughput genotyping and phenotyping platforms, statistical models, and the utilization of MTAs in breeding programs. Future breakthroughs in genomic selection, multi-omics-based approaches, and machine and deep learning models in wheat breeding are also discussed.
MOLECULAR BREEDING
(2022)
Article
Statistics & Probability
Haoran Xue, Xiaotong Shen, Wei Pan
Summary: Transcriptome-Wide Association Studies (TWAS) have become popular to discover (putative) causal genes by integrating outcome GWAS and eQTL datasets. In the specific application of identifying causal genes for LDL cholesterol, a robust and efficient inferential method is proposed to account for hidden confounding and invalid instrumental variables.
JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION
(2023)
Article
Multidisciplinary Sciences
Ruidong Xiang, Iona M. MacLeod, Hans D. Daetwyler, Gerben de Jong, Erin O'Connor, Chris Schrooten, Amanda J. Chamberlain, Michael E. Goddard
Summary: This study presents a method for fine-mapping potentially causal mutations by integrating functional, evolutionary, and pleiotropic information and developing a custom genotyping array. The custom array, containing variants with biological functions, outperformed the standard array in predicting genetic values for multiple traits in dairy cattle populations across different countries. This highlights the potential improvement in genomic prediction by utilizing mutations with functional, evolutionary, and pleiotropic consequences.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Zihuai He, Linxi Liu, Michael E. Belloy, Yann Le Guen, Aaron Sossin, Xiaoxia Liu, Xinran Qi, Shiyang Ma, Prashnna K. Gyawali, Tony Wyss-Coray, Hua Tang, Chiara Sabatti, Emmanuel Candes, Michael D. Greicius, Iuliana Ionita-Laza
Summary: The authors present GhostKnockoff, a method for genome-wide association studies which can be applied to enhance existing and future studies to identify functional variants with weaker statistical effects that might be missed by conventional association tests.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Brian M. Schilder, Towfique Raj
Summary: This study identified likely causal variants associated with Parkinson's disease susceptibility through fine-mapping methods and integrated epigenomic profiles to reveal the potential mechanism of action of these variants. The comprehensive list provided by this study may serve as targets in the development of more effective Parkinson's therapeutics.
HUMAN MOLECULAR GENETICS
(2022)
Article
Genetics & Heredity
Jeremy Schwartzentruber, Sarah Cooper, Jimmy Z. Liu, Inigo Barrio-Hernandez, Erica Bello, Natsuhiko Kumasaka, Adam M. H. Young, Robin J. M. Franklin, Toby Johnson, Karol Estrada, Daniel J. Gaffney, Pedro Beltrao, Andrew Bassett
Summary: A genome-wide AD meta-analysis identified 37 risk loci, including new associations near CCDC6, TSPAN14, NCK2, and SPRED2. By fine-mapping SNPs and using functional annotation, 21 SNPs with >50% probability of being causally involved in AD risk were identified. Protein interaction networks and tissue-specific expression helped prioritize genes, leading to the discovery of likely causal genes.
Article
Multidisciplinary Sciences
Yuyan Qian, Jianhu Wang, Wenbin wANG, Peng li, Zhenhao Zhao, Yuan Jiang, Dandan Huang, He Ren, Yang Yang, Zhongfan Zhao, Lei Zhang, Jiandan Shi, Mulin Jun, Wangee Li
Summary: Using fine-mapping analysis and functional annotation, we identified likely causal variants and their target genes in prostate cancer. We found 3,395 potential disease-causing variants and linked them to 487 target genes through functional annotation. The top-ranked SNP, rs10486567, was predicted to regulate the HOTTIP gene. Deletion of the enhancer associated with rs10486567 reduced invasive migration in prostate cancer cells, which was rescued by HOTTIP overexpression in enhancer-deficient cells. Furthermore, rs10486567 was found to regulate HOTTIP through allele-specific long-range chromatin interaction.
Article
Genetics & Heredity
Alison R. Barton, Maxwell A. Sherman, Ronen E. Mukamel, Po-Ru Loh
Summary: This study leveraged haplotype sharing in the UK Biobank to impute exome-wide variants and identified significant associations involving rare protein-altering variants. The research revealed significant associations in multiple genes and proposed allelic series containing multiple "likely-causal" variants.
Article
Genetics & Heredity
Xing Wu, Wei Jiang, Christopher Fragoso, Jing Huang, Geyu Zhou, Hongyu Zhao, Stephen Dellaporta
Summary: Genome-wide association studies (GWAS) are crucial for understanding the genetic basis of complex traits in plants and animals. However, mapping complex traits in plant GWAS can be challenging due to small population size and high genetic diversity. In this study, a novel haplotype-based trait fine-mapping framework, HapFM, was introduced to overcome these challenges and improve mapping power and resolution. HapFM consistently outperformed other GWAS methods in both simulated and real plant GWAS datasets, resulting in smaller mapping intervals and identifying novel loci. HapFM is tailored for plant GWAS and can facilitate crop improvement.
Article
Multidisciplinary Sciences
Qingbo S. Wang, David R. Kelley, Jacob Ulirsch, Masahiro Kanai, Shuvom Sadhuka, Ran Cui, Carlos Albors, Nathan Cheng, Yukinori Okada, Francois Aguet, Kristin G. Ardlie, Daniel G. MacArthur, Hilary K. Finucane
Summary: The authors trained a model to predict if a variant affects nearby gene expression, and applied the method to identify new possible causal eQTLs and mechanisms of GWAS loci.
NATURE COMMUNICATIONS
(2021)
Article
Genetics & Heredity
Haniel C. Oliveira, Martijn F. L. Derks, Marcos S. Lopes, Ole Madsen, Barbara Harlizius, Maren van Son, Eli H. Grindflek, Marta Godia, Arne B. Gjuvsland, Pamela Itajara Otto, Martien A. M. Groenen, Simone E. F. Guimaraes
Summary: Backfat is an important trait in pork production, and excessive fat can result in economic losses. Through genome-wide association analysis, we identified a QTL for backfat thickness located within the third intron of the CCND2 gene, and further discovered core haplotypes associated with low backfat.
FRONTIERS IN GENETICS
(2022)
Article
Genetics & Heredity
Guhan Ram Venkataraman, Christopher DeBoever, Yosuke Tanigawa, Matthew Aguirre, Alexander G. Ioannidis, Hakhamanesh Mostafavi, Chris C. A. Spencer, Timothy Poterba, Carlos D. Bustamante, Mark J. Daly, Matti Pirinen, Manuel A. Rivas
Summary: The study introduces a Bayesian model comparison approach called MRP for rare-variant association studies, which can effectively detect associations between genes and multiple phenotypes, providing new opportunities for discovery. When applied to large-scale population sequencing data, the MRP method shows improved signal recovery capabilities and significant effectiveness in meta-analyses of exome data.
AMERICAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Multidisciplinary Sciences
Matthieu Bouaziz, Jimmy Mullaert, Benedetta Bigio, Yoann Seeleuthner, Jean-Laurent Casanova, Alexandre Alcai, Laurent Abel, Aurelie Cobat
Summary: Population stratification is a confounder of genetic association studies, especially in analyses of rare variants. Correction methods based on principal components and linear mixed models may yield conflicting conclusions. A simulation study involving various population structures and sample sizes found that a novel local permutation method maintained correct type-I-errors across all scenarios. Properly controlling type-I-errors is crucial in genetic association studies involving population stratification.
SCIENTIFIC REPORTS
(2021)
Review
Oncology
Susan M. Gapstur, Elisa Bandera, David H. Jernigan, Noelle K. LoConte, Brian G. Southwell, Vasilis Vasiliou, Abenaa M. Brewster, Timothy S. Naimi, Courtney L. Scherr, Kevin D. Shield
Summary: Alcoholic beverages are carcinogenic to humans, but the full cancer burden due to alcohol is uncertain. The associations of alcohol consumption with treatment response, disease progression, and long-term prognosis are unclear, and public awareness of the alcohol-cancer link is lacking. The impact of alcohol control policies on cancer risk is also unclear. Interdisciplinary research and interventions are needed to increase knowledge, raise awareness, and reduce harmful consumption to decrease the alcohol-related cancer burden.
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2022)
Article
Oncology
Lauren C. Peres, Christelle Colin-Leitzinger, Sweta Sinha, Jeffrey R. Marks, Jose R. Conejo-Garcia, Anthony J. Alberg, Elisa Bandera, Andrew Berchuck, Melissa L. Bondy, Brock C. Christensen, Michele L. Cote, Jennifer Anne Doherty, Patricia G. Moorman, Edward S. Peters, Carlos Moran Segura, Jonathan Nguyen, Ann G. Schwartz, Paul D. Terry, Christopher M. Wilson, Brooke L. Fridley, Joellen M. Schildkraut
Summary: This study found that tumor-infiltrating lymphocytes confer a survival benefit among patients with ovarian cancer, but little work has been conducted in racially diverse cohorts. Non-Hispanic Black women may not experience the same survival benefit as Non-Hispanic White women with high-grade serous ovarian carcinoma (HGSOC).
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2022)
Article
Oncology
Holly R. Harris, Kristin A. Guertin, Tareq F. Camacho, Courtney E. Johnson, Anna H. Wu, Patricia G. Moorman, Evan Myers, Traci N. Bethea, Elisa Bandera, Charlotte E. Joslin, Heather M. Ochs-Balcom, Lauren C. Peres, Will T. Rosenow, Veronica W. Setiawan, Alicia Beeghly-Fadiel, Lauren F. Dempsey, Lynn Rosenberg, Joellen M. Schildkraut
Summary: Black women diagnosed with epithelial ovarian cancer have lower survival rates compared to white women. Factors such as education, lifestyle, diabetes, hormone therapy, and tumor characteristics contribute to this disparity.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Article
Oncology
Rebecca Nash, Courtney E. Johnson, Holly R. Harris, Lauren C. Peres, Charlotte E. Joslin, Traci N. Bethea, Elisa Bandera, Heather M. Ochs-Balcom, Evan R. Myers, Kristin A. Guertin, Fabian Camacho, Alicia Beeghly-Fadiel, Patricia G. Moorman, V. Wendy Setiawan, Lynn Rosenberg, Joellen M. Schildkraut, Anna H. Wu
Summary: Earlier age at menarche and irregular menstrual cycles are associated with increased ovarian cancer risk among White women, but not among Black women.
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2022)
Article
Oncology
Saber A. Amin, Lindsay J. Collin, Soko Setoguchi, Jaya M. Satagopan, Alexandre Buckley de Meritens, Elisa V. Bandera
Summary: This study examined racial and ethnic disparities in treatment sequence and mortality among ovarian cancer patients. The results showed that non-Hispanic Black and Asian women were more likely to receive neoadjuvant chemotherapy plus interval debulking surgery, while non-Hispanic White women more often had primary debulking surgery plus adjuvant chemotherapy. Non-Hispanic Black women had a higher risk of all-cause mortality, while Asian and Hispanic women had a lower risk, and these disparities were not explained by treatment sequence.
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2023)
Article
Psychiatry
Jinghan Huang, Qiushan Tao, Ting Fang Alvin Ang, John Farrell, Congcong Zhu, Yixuan Wang, Thor D. Stein, Kathryn L. Lunetta, Joseph Massaro, Jesse Mez, Rhoda Au, Lindsay A. Farrer, Wei Qiao Qiu, Xiaoling Zhang
Summary: APOE E4 is the most significant genetic risk factor for late-onset Alzheimer's disease (AD), and elevated blood C-reactive protein (CRP) levels further increase this risk. This study found that CRP can modulate the impact of other inflammatory genes, especially SPI1 and CD33, on AD risk.
TRANSLATIONAL PSYCHIATRY
(2022)
Article
Oncology
Hari S. Iyer, Kevin H. Kensler, Jane B. Vaselkiv, Konrad H. Stopsack, Charlotte Roscoe, Elisa V. Bandera, Bo Qin, Thomas L. Jang, Tamara L. Lotan, Peter James, Jaime E. Hart, Lorelei A. Mucci, Francine Laden, Timothy R. Rebbeck
Summary: There is growing evidence that unfavorable neighborhood contexts may influence prostate cancer progression. However, it is unclear whether these associations can be partially explained by differences in tumor-level somatic alterations.
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2023)
Article
Oncology
Kate Gersekowski, Torukiri I. Ibiebele, Jennifer A. Doherty, Holly R. Harris, Marc T. Goodman, Kathryn L. Terry, Anna H. Wu, Elisa V. Bandera, Bo Qin, Jue-Sheng Ong, Jonathan P. Tyrer, Suzanne C. Dixon-Suen, Francesmary Modugno, Harvey A. Risch, Penelope M. Webb
Summary: A pooled analysis of case-control studies suggests that high dietary folate intake may increase the risk of ovarian cancer in women with endometriosis. Further research is needed to explore the potential cancer-promoting effects of folate in this population.
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2023)
Article
Genetics & Heredity
Sean J. J. Jurgens, James P. P. Pirruccello, Seung Hoan Choi, Valerie N. N. Morrill, Mark Chaffin, Steven A. A. Lubitz, Kathryn L. L. Lunetta, Patrick T. T. Ellinor
Summary: With the emergence of large-scale sequencing data, methods for improving power in rare variant association tests are needed. We show that adjusting for common variant polygenic scores improves yield in gene-based rare variant association tests for quantitative traits, particularly when using sparse mixed models or simple linear models as an alternative to dense mixed-model approaches.
Article
Oncology
Jessica L. Petrick, Charlotte E. Joslin, Courtney E. Johnson, T. Fabian Camacho, Lauren C. Peres, Elisa V. Bandera, Mollie E. Barnard, Alicia Beeghly, Traci N. Bethea, Lauren F. Dempsey, Kristin Guertin, Holly R. Harris, Patricia G. Moorman, Evan R. Myers, Heather M. Ochs-Balcom, Will Rosenow, V. Wendy Setiawan, Anna H. Wu, Joellen M. Schildkraut, Lynn Rosenberg
Summary: The association between long-term MHT use and ovarian cancer risk was consistent for Black and White women. The increased risk was mainly observed in high-grade serous and endometroid tumors in White women, while it was specifically associated with other epithelial histotypes in Black women.
BRITISH JOURNAL OF CANCER
(2023)
Article
Clinical Neurology
Lu-Chen Weng, Shaan Khurshid, Sophia Gunn, Ludovic L. Trinquart, Kathryn Lunetta, Huichun J. Xu, Patrick T. NINDS Stroke Genetics Network, Emelia D. Benjamin, Patrick A. Ellinor, Christopher Anderson, Steven Lubitz
Summary: The polygenic risk score for atrial fibrillation can help distinguish between cardioembolic and noncardioembolic strokes. It improves the discrimination and reclassification of stroke subtypes when combined with clinical risk factors.
Article
Oncology
Ting-Yuan David Cheng, Runzhi Zhang, Zhihong Gong, Bo Qin, Rikki A. Cannioto, Susmita Datta, Weizhou Zhang, Angela R. Omilian, Song Yao, Thaer Khoury, Chi-Chen Hong, Elisa V. Bandera, Christine B. Ambrosone
Summary: Physical activity has been shown to be associated with decreased mTOR pathway signaling in animal models of mammary cancer. This study examined the association between physical activity and protein expression in the mTOR signaling pathway in breast tumor tissue. The results suggest that guideline-concordant physical activity levels are associated with increased mTOR signaling pathway activity in breast tumors.
CANCER RESEARCH COMMUNICATIONS
(2023)
Meeting Abstract
Oncology
Holly Harris, Lauren Peres, Courtney Johnson, Kristin Guertin, Alicia Beeghly-Fadiel, Elisa Bandera, Traci Bethea, Charlotte Joslin, Anna Wu, Patricia Moorman, Heather Ochs-Balcom, Jessica Petrick, Veronica Setiawan, Lynn Rosenberg, Joellen Schildkraut, Evan Myers
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2023)
Meeting Abstract
Oncology
Michelle Doose, Janeth I. Sanchez, Dana Verhoeven, Veronica Chollette, Joel C. Cantor, Jesse J. Plascak, Michael Steinberg, Chi-Chen Hong, Kitaw Demissie, Elisa Bandera, Jennifer Tsui, Sallie J. Weaver
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2022)
Article
Nutrition & Dietetics
Susan E. McCann, Elisa M. Rodriguez, Deborah Erwin, Song Yao, David Tritchler, Meredith A. J. Hullar, Tracey O'Connor, Johanna W. Lampe
Summary: This study examines the barriers and successes of recruitment and retention strategies for dietary studies, particularly in recruiting minority participants. The study found that direct community-based strategies were effective in recruiting a diverse population, with African American women responding more to these methods. However, retention of African American women was lower compared to European American women.
CURRENT DEVELOPMENTS IN NUTRITION
(2022)