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1. Determinants of mosaic chromosomal alteration fitness.

Author

Pershad, Yash, Mack, Taralynn, Poisner, Hannah, Jakubek, Yasminka, Stilp, Adrienne, Mitchell, Braxton, Lewis, Joshua, Boerwinkle, Eric, Loos, Ruth, Chami, Nathalie, Wang, Zhe, Barnes, Kathleen, Pankratz, Nathan, Fornage, Myriam, Redline, Susan, Psaty, Bruce, Bis, Joshua, Shojaie, Ali, Silverman, Edwin, Cho, Michael, Yun, Jeong, DeMeo, Dawn, Levy, Daniel, Johnson, Andrew, Mathias, Rasika, Taub, Margaret, Arnett, Donna, North, Kari, Raffield, Laura, Carson, April, Doyle, Margaret, Rich, Stephen, Guo, Xiuqing, Cox, Nancy, Roden, Dan, Franceschini, Nora, Desai, Pinkal, Reiner, Alex, Auer, Paul, Scheet, Paul, Jaiswal, Siddhartha, Weinstock, Joshua, Bick, Alexander, and Rotter, Jerome

Subjects
Humans, Mosaicism, Chromosome Aberrations, Clonal Hematopoiesis, Male, Female, Genome-Wide Association Study, Janus Kinase 2, Telomerase, Loss of Heterozygosity, Cross-Sectional Studies, Mutation, Middle Aged, Hematopoietic Stem Cells, Polymorphism, Single Nucleotide, Aged
Abstract

Clonal hematopoiesis (CH) is characterized by the acquisition of a somatic mutation in a hematopoietic stem cell that results in a clonal expansion. These driver mutations can be single nucleotide variants in cancer driver genes or larger structural rearrangements called mosaic chromosomal alterations (mCAs). The factors that influence the variations in mCA fitness and ultimately result in different clonal expansion rates are not well understood. We used the Passenger-Approximated Clonal Expansion Rate (PACER) method to estimate clonal expansion rate as PACER scores for 6,381 individuals in the NHLBI TOPMed cohort with gain, loss, and copy-neutral loss of heterozygosity mCAs. Our mCA fitness estimates, derived by aggregating per-individual PACER scores, were correlated (R2 = 0.49) with an alternative approach that estimated fitness of mCAs in the UK Biobank using population-level distributions of clonal fraction. Among individuals with JAK2 V617F clonal hematopoiesis of indeterminate potential or mCAs affecting the JAK2 gene on chromosome 9, PACER score was strongly correlated with erythrocyte count. In a cross-sectional analysis, genome-wide association study of estimates of mCA expansion rate identified a TCL1A locus variant associated with mCA clonal expansion rate, with suggestive variants in NRIP1 and TERT.

Published
2024

2. Mosaic chromosomal alterations in blood across ancestries using whole-genome sequencing.

Author

Jakubek, Yasminka, Zhou, Ying, Stilp, Adrienne, Bacon, Jason, Wong, Justin, Ozcan, Zuhal, Arnett, Donna, Barnes, Kathleen, Bis, Joshua, Boerwinkle, Eric, Brody, Jennifer, Carson, April, Chasman, Daniel, Chen, Jiawen, Cho, Michael, Conomos, Matthew, Cox, Nancy, Doyle, Margaret, Fornage, Myriam, Guo, Xiuqing, Kardia, Sharon, Lewis, Joshua, Loos, Ruth, Ma, Xiaolong, Machiela, Mitchell, Mack, Taralynn, Mathias, Rasika, Mitchell, Braxton, Mychaleckyj, Josyf, North, Kari, Pankratz, Nathan, Peyser, Patricia, Preuss, Michael, Psaty, Bruce, Raffield, Laura, Vasan, Ramachandran, Redline, Susan, Rich, Stephen, Silverman, Edwin, Smith, Jennifer, Smith, Aaron, Taub, Margaret, Taylor, Kent, Yun, Jeong, Li, Yun, Desai, Pinkal, Bick, Alexander, Reiner, Alexander, Scheet, Paul, Auer, Paul, and Rotter, Jerome

Subjects
Humans, Black People, Genome-Wide Association Study, Hispanic or Latino, Precision Medicine, Mosaicism, Genome, Human
Abstract

Megabase-scale mosaic chromosomal alterations (mCAs) in blood are prognostic markers for a host of human diseases. Here, to gain a better understanding of mCA rates in genetically diverse populations, we analyzed whole-genome sequencing data from 67,390 individuals from the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine program. We observed higher sensitivity with whole-genome sequencing data, compared with array-based data, in uncovering mCAs at low mutant cell fractions and found that individuals of European ancestry have the highest rates of autosomal mCAs and the lowest rates of chromosome X mCAs, compared with individuals of African or Hispanic ancestry. Although further studies in diverse populations will be needed to replicate our findings, we report three loci associated with loss of chromosome X, associations between autosomal mCAs and rare variants in DCPS, ADM17, PPP1R16B and TET2 and ancestry-specific variants in ATM and MPL with mCAs in cis.

Published
2023

3. An atlas of epithelial cell states and plasticity in lung adenocarcinoma

Author

Han, Guangchun, Sinjab, Ansam, Rahal, Zahraa, Lynch, Anne M., Treekitkarnmongkol, Warapen, Liu, Yuejiang, Serrano, Alejandra G., Feng, Jiping, Liang, Ke, Khan, Khaja, Lu, Wei, Hernandez, Sharia D., Liu, Yunhe, Cao, Xuanye, Dai, Enyu, Pei, Guangsheng, Hu, Jian, Abaya, Camille, Gomez-Bolanos, Lorena I., Peng, Fuduan, Chen, Minyue, Parra, Edwin R., Cascone, Tina, Sepesi, Boris, Moghaddam, Seyed Javad, Scheet, Paul, Negrao, Marcelo V., Heymach, John V., Li, Mingyao, Dubinett, Steven M., Stevenson, Christopher S., Spira, Avrum E., Fujimoto, Junya, Solis, Luisa M., Wistuba, Ignacio I., Chen, Jichao, Wang, Linghua, and Kadara, Humam

Published
2024
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5. Transcriptome- and proteome-wide association studies identify genes associated with renal cell carcinoma

Author

Purdue, Mark P., Dutta, Diptavo, Machiela, Mitchell J., Gorman, Bryan R., Winter, Timothy, Okuhara, Dayne, Cleland, Sara, Ferreiro-Iglesias, Aida, Scheet, Paul, Liu, Aoxing, Wu, Chao, Antwi, Samuel O., Larkin, James, Zequi, Stênio C., Sun, Maxine, Hikino, Keiko, Hajiran, Ali, Lawson, Keith A., Cárcano, Flavio, Blanchet, Odile, Shuch, Brian, Nepple, Kenneth G., Margue, Gaëlle, Sundi, Debasish, Diver, W. Ryan, Folgueira, Maria A.A.K., van Bokhoven, Adrie, Neffa, Florencia, Brown, Kevin M., Hofmann, Jonathan N., Rhee, Jongeun, Yeager, Meredith, Cole, Nathan R., Hicks, Belynda D., Manning, Michelle R., Hutchinson, Amy A., Rothman, Nathaniel, Huang, Wen-Yi, Linehan, W. Marston, Lori, Adriana, Ferragu, Matthieu, Zidane-Marinnes, Merzouka, Serrano, Sérgio, Magnabosco, Wesley J., BioBank Japan Project Consortium, Vilas, Ana, Decia, Ricardo, Carusso, Florencia, Graham, Laura S., Anderson, Kyra, Bilen, Mehmet A., Arciero, Cletus, Pellegrin, Isabelle, Ricard, Solène, FinnGen, Scelo, Ghislaine, Banks, Rosamonde E., Vasudev, Naveen S., Soomro, Naeem, Stewart, Grant D., Adeyoju, Adebanji, Bromage, Stephen, Hrouda, David, Gibbons, Norma, Patel, Poulam, Sullivan, Mark, Protheroe, Andrew, Nugent, Francesca I., Fournier, Michelle J., Zhang, Xiaoyu, Martin, Lisa J., Komisarenko, Maria, Eisen, Timothy, Cunningham, Sonia A., Connolly, Denise C., Uzzo, Robert G., Zaridze, David, Mukeria, Anush, Holcatova, Ivana, Hornakova, Anna, Foretova, Lenka, Janout, Vladimir, Mates, Dana, Jinga, Viorel, Rascu, Stefan, Mijuskovic, Mirjana, Savic, Slavisa, Milosavljevic, Sasa, Gaborieau, Valérie, Abedi-Ardekani, Behnoush, McKay, James, Johansson, Mattias, Phouthavongsy, Larry, Hayman, Lindsay, Li, Jason, Lungu, Ilinca, Bezerra, Stephania M., de Souza, Aline G., Sares, Claudia T.G., Reis, Rodolfo B., Gallucci, Fabio P., Cordeiro, Mauricio D., Pomerantz, Mark, Lee, Gwo-Shu M., Freedman, Matthew L., Jeong, Anhyo, Greenberg, Samantha E., Sanchez, Alejandro, Thompson, R. Houston, Sharma, Vidit, Thiel, David D., Ball, Colleen T., Abreu, Diego, Lam, Elaine T., Nahas, William C., Master, Viraj A., Patel, Alpa V., Bernhard, Jean-Christophe, Freedman, Neal D., Bigot, Pierre, Reis, Rui M., Colli, Leandro M., Finelli, Antonio, Manley, Brandon J., Terao, Chikashi, Choueiri, Toni K., Carraro, Dirce M., Houlston, Richard, Eckel-Passow, Jeanette E., Abbosh, Philip H., Ganna, Andrea, Brennan, Paul, Gu, Jian, Chanock, Stephen J., Guo, Xinyu, Winter, Timothy D., Jahagirdar, Om, Ha, Eunji, and Susztak, Katalin

Published
2024
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6. Association of clonal hematopoiesis mutations with clinical outcomes: A systematic review and meta‐analysis

Author

Nowakowska, Malgorzata K, Kim, Taebeom, Thompson, Mikayla T, Bolton, Kelly L, Deswal, Anita, Lin, Steven H, Scheet, Paul, Wehner, Mackenzie R, and Nead, Kevin T

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Hematology, Cancer, Clinical Research, Cardiovascular, Good Health and Well Being, Alleles, Clonal Hematopoiesis, Hematologic Neoplasms, Hematopoiesis, Humans, Mutation, Neoplasms, Second Primary, Cardiorespiratory Medicine and Haematology, Immunology, Cardiovascular medicine and haematology
Abstract

Clonal hematopoiesis (CH) mutations are common among individuals without known hematologic disease. CH mutations have been associated with numerous adverse clinical outcomes across many different studies. We systematically reviewed the available literature for clinical outcomes associated with CH mutations in patients without hematologic disease. We searched PubMed, EMBASE, and Scopus for eligible studies. Three investigators independently extracted the data, and each study was verified by a second author. Risk of bias was assessed using the Newcastle-Ottawa Scale. We identified 32 studies with 56 cohorts that examine the association between CH mutations and clinical outcomes. We conducted meta-analyses comparing outcomes among individuals with and without detectable CH mutations. We conducted meta-analyses for cardiovascular diseases (nine studies; HR = 1.61, 95% CI = 1.26-2.07, p = .0002), hematologic malignancies (seven studies; HR = 5.59, 95% CI = 3.31-9.45, p

Published
2022

7. Author Correction: An atlas of epithelial cell states and plasticity in lung adenocarcinoma

Author

Han, Guangchun, Sinjab, Ansam, Rahal, Zahraa, Lynch, Anne M., Treekitkarnmongkol, Warapen, Liu, Yuejiang, Serrano, Alejandra G., Feng, Jiping, Liang, Ke, Khan, Khaja, Lu, Wei, Hernandez, Sharia D., Liu, Yunhe, Cao, Xuanye, Dai, Enyu, Pei, Guangsheng, Hu, Jian, Abaya, Camille, Gomez-Bolanos, Lorena I., Peng, Fuduan, Chen, Minyue, Parra, Edwin R., Cascone, Tina, Sepesi, Boris, Moghaddam, Seyed Javad, Scheet, Paul, Negrao, Marcelo V., Heymach, John V., Li, Mingyao, Dubinett, Steven M., Stevenson, Christopher S., Spira, Avrum E., Fujimoto, Junya, Solis, Luisa M., Wistuba, Ignacio I., Chen, Jichao, Wang, Linghua, and Kadara, Humam

Published
2024
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8. Resolving the spatial and cellular architecture of lung adenocarcinoma by multiregion single-cell sequencing

Author

Sinjab, Ansam, Han, Guangchun, Treekitkarnmongkol, Warapen, Hara, Kieko, Brennan, Patrick M, Dang, Minghao, Hao, Dapeng, Wang, Ruiping, Dai, Enyu, Dejima, Hitoshi, Zhang, Jiexin, Bogatenkova, Elena, Sanchez-Espiridion, Beatriz, Chang, Kyle, Little, Danielle R, Bazzi, Samer, Tran, Linh M, Krysan, Kostyantyn, Behrens, Carmen, Duose, Dzifa Y, Parra, Edwin R, Raso, Maria Gabriela, Solis, Luisa M, Fukuoka, Junya, Zhang, Jianjun, Sepesi, Boris, Cascone, Tina, Byers, Lauren Averett, Gibbons, Don L, Chen, Jichao, Moghaddam, Seyed Javad, Ostrin, Edwin J, Rosen, Daniel, Heymach, John V, Scheet, Paul, Dubinett, Steven M, Fujimoto, Junya, Wistuba, Ignacio I, Stevenson, Christopher S, Spira, Avrum, Wang, Linghua, and Kadara, Humam

Subjects
Biomedical and Clinical Sciences, Immunology, Rare Diseases, Lung Cancer, Lung, Genetics, Cancer, 1.1 Normal biological development and functioning, Underpinning research, Good Health and Well Being, Adenocarcinoma of Lung, CD8-Positive T-Lymphocytes, Humans, Lung Neoplasms, Single-Cell Analysis, Tumor Microenvironment, Oncology and Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Little is known of the geospatial architecture of individual cell populations in lung adenocarcinoma (LUAD) evolution. Here, we perform single-cell RNA sequencing of 186,916 cells from five early-stage LUADs and 14 multiregion normal lung tissues of defined spatial proximities from the tumors. We show that cellular lineages, states, and transcriptomic features geospatially evolve across normal regions to LUADs. LUADs also exhibit pronounced intratumor cell heterogeneity within single sites and transcriptional lineage-plasticity programs. T regulatory cell phenotypes are increased in normal tissues with proximity to LUAD, in contrast to diminished signatures and fractions of cytotoxic CD8+ T cells, antigen-presenting macrophages, and inflammatory dendritic cells. We further find that the LUAD ligand-receptor interactome harbors increased expression of epithelial CD24, which mediates protumor phenotypes. These data provide a spatial atlas of LUAD evolution, and a resource for identification of targets for its treatment. SIGNIFICANCE: The geospatial ecosystem of the peripheral lung and early-stage LUAD is not known. Our multiregion single-cell sequencing analyses unravel cell populations, states, and phenotypes in the spatial and ecologic evolution of LUAD from the lung that comprise high-potential targets for early interception.This article is highlighted in the In This Issue feature, p. 2355.

Published
2021

9. Modulating a prebiotic food source influences inflammation and immune-regulating gut microbes and metabolites: insights from the BE GONE trial

Author

Zhang, Xiaotao, Irajizad, Ehsan, Hoffman, Kristi L., Fahrmann, Johannes F., Li, Fangyu, Seo, Yongwoo David, Browman, Gladys J., Dennison, Jennifer B., Vykoukal, Jody, Luna, Pamela N., Siu, Wesley, Wu, Ranran, Murage, Eunice, Ajami, Nadim J., McQuade, Jennifer L., Wargo, Jennifer A., Long, James P., Do, Kim-Anh, Lampe, Johanna W., Basen-Engquist, Karen M., Okhuysen, Pablo C., Kopetz, Scott, Hanash, Samir M., Petrosino, Joseph F., Scheet, Paul, and Daniel, Carrie R.

Published
2023
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10. Clinical Characteristics and Cause of Death Among Hospitalized Decedents With Cancer and COVID-19

Author

Aaroe, Ashley, Aloia, Thomas A., Andrews, Lee, II, Badami, Kiran K., Baganz, Janna A., Bajwa, Pratibha, Baker, Lori R., Barbosa, Gregory R., Beird, Hannah C., Bourgeois, Matt, Brock, Kristy, Burton, Elizabeth M., Cata, Juan, Chung, Caroline, Cutherell, Michael, Cuenca, John A., Cyr, Pierre B., Dabaja, Bouthaina, Dagher, Hiba, Daniels, Kevin M., Domask, Mary, Draetta, Giulio, Fisher, Sarah, French, Katy Elizabeth, Futreal, Andrew, Gaeta, Maria, Gibbons, Christopher, Godoy, Myrna, Goldstein, Drew, Gunther, Jillian, Hernandez, Cristhiam, Hutcheson, Kate, Jaffray, David, Jin, Jeff, John, Teny Matthew, Kell, Trey, Knafl, Mark, Kothari, Anai, Kwan, Rayson C., Lee, J. Jack, Liao, Yue, Litton, Jennifer, Liu, Alex, McEnery, Kevin W., McGuire, Mary, Musunuru, Tego, Muthu, Mayoora, Nates, Joseph L., Owen, Craig S., Padmakumar, Priyadharshini, Page, Melody, Palaskas, Nicholas, Patel, Jay J., Prabhakaran, Sabitha, Ravi, Vinod, Russell, Ludivine, Sajith, Bilja, Scheet, Paul A., Schmidt, Stephanie, Shaw, Kenna R., Shete, Sanjay, Shoenthal, Daniel P., Stoltenberg, Lessley J., Subbiah, Ishwaria, Suitor, Chuck, Tawbi, Hussein, Thompson, Phillip, Turin, Anastasia, Unni, Samir, Vicknamparampil, Benju, Weber, Max C., Weinstein, John, Williams, Zoe, Woodman, Scott E., Wozny, Mark C., Wu, Carol, Wu, Jia, Yao, James C., Young, Chingyi, Yu, Emily, Zatorski, Steven, Reddy, Dereddi Raja, Botdorf, Joshua, Hanmandlu, Ankit, Wegner, Robert, Crommett, John, Gutierrez, Cristina, Rathi, Nisha, and Abbas, Hussein A.

Published
2023
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11. RAD21 promotes oncogenesis and lethal progression of prostate cancer.

Author

Xiaofeng A. Su, Stopsack, Konrad H., Schmidt, Daniel R., Duanduan Ma, Zhe Li, Scheet, Paul A., Penney, Kathryn L., Lotan, Tamara L., Abida, Wassim, DeArment, Elise G., Lu, Kate, Janas, Thomas, Hu, Sofia, Vander Heiden, Matthew G., Loda, Massimo, Boselli, Monica, Amon, Angelika, and Mucci, Lorelei A.

Subjects
PROSTATE cancer prognosis, GENE expression, PROSTATE tumors, PROSTATE cancer, GLEASON grading system, PROSTATE cancer patients
Abstract

Higher levels of aneuploidy, characterized by imbalanced chromosome numbers, are associated with lethal progression in prostate cancer. However, how aneuploidy contributes to prostate cancer aggressiveness remains poorly understood. In this study, we assessed in patients which genes on chromosome 8q, one of the most frequently gained chromosome arms in prostate tumors, were most strongly associated with long-term risk of cancer progression to metastases and death from prostate cancer (lethal disease) in 403 patients and found the strongest candidate was cohesin subunit gene, RAD21, with an odds ratio of 3.7 (95% CI 1.8, 7.6) comparing the highest vs. lowest tertiles of mRNA expression and adjusting for overall aneuploidy burden and Gleason score, both strong prognostic factors in primary prostate cancer. Studying prostate cancer driven by the TMPRSS2-ERG oncogenic fusion, found in about half of all prostate tumors, we found that increased RAD21 alleviated toxic oncogenic stress and DNA damage caused by oncogene expression. Data from both organoids and patients indicate that increased RAD21 thereby enables aggressive tumors to sustain tumor proliferation, and more broadly suggests one path through which tumors benefit from aneuploidy. [ABSTRACT FROM AUTHOR]

Published
2024
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12. Evolution of DNA methylome from precancerous lesions to invasive lung adenocarcinomas

Author

Hu, Xin, Estecio, Marcos R., Chen, Runzhe, Reuben, Alexandre, Wang, Linghua, Fujimoto, Junya, Carrot-Zhang, Jian, McGranahan, Nicholas, Ying, Lisha, Fukuoka, Junya, Chow, Chi-Wan, Pham, Hoa H. N., Godoy, Myrna C. B., Carter, Brett W., Behrens, Carmen, Zhang, Jianhua, Antonoff, Mara B., Sepesi, Boris, Lu, Yue, Pass, Harvey I., Kadara, Humam, Scheet, Paul, Vaporciyan, Ara A., Heymach, John V., Wistuba, Ignacio I., Lee, J. Jack, Futreal, P. Andrew, Su, Dan, Issa, Jean-Pierre J., and Zhang, Jianjun

Published
2021
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13. Author Correction: Multi-region exome sequencing reveals genomic evolution from preneoplasia to lung adenocarcinoma

Author

Hu, Xin, Fujimoto, Junya, Ying, Lisha, Fukuoka, Junya, Ashizawa, Kazuto, Sun, Wenyong, Reuben, Alexandre, Chow, Chi-Wan, McGranahan, Nicholas, Chen, Runzhe, Hu, Jinlin, Godoy, Myrna C., Tabata, Kazuhiro, Kuroda, Kishio, Shi, Lei, Li, Jun, Behrens, Carmen, Parra, Edwin Roger, Little, Latasha D., Gumbs, Curtis, Mao, Xizeng, Song, Xingzhi, Tippen, Samantha, Thornton, Rebecca L., Kadara, Humam, Scheet, Paul, Roarty, Emily, Ostrin, Edwin Justin, Wang, Xu, Carter, Brett W., Antonoff, Mara B., Zhang, Jianhua, Vaporciyan, Ara A., Pass, Harvey, Swisher, Stephen G., Heymach, John V., Lee, J. Jack, Wistuba, Ignacio I., Hong, Waun Ki, Futreal, P. Andrew, Su, Dan, and Zhang, Jianjun

Published
2021
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14. Immune evolution from preneoplasia to invasive lung adenocarcinomas and underlying molecular features

Author

Dejima, Hitoshi, Hu, Xin, Chen, Runzhe, Zhang, Jiexin, Fujimoto, Junya, Parra, Edwin R., Haymaker, Cara, Hubert, Shawna M., Duose, Dzifa, Solis, Luisa M., Su, Dan, Fukuoka, Junya, Tabata, Kazuhiro, Pham, Hoa H. N., Mcgranahan, Nicholas, Zhang, Baili, Ye, Jie, Ying, Lisha, Little, Latasha, Gumbs, Curtis, Chow, Chi-Wan, Estecio, Marcos Roberto, Godoy, Myrna C. B., Antonoff, Mara B., Sepesi, Boris, Pass, Harvey I., Behrens, Carmen, Zhang, Jianhua, Vaporciyan, Ara A., Heymach, John V., Scheet, Paul, Lee, J. Jack, Wu, Jia, Futreal, P. Andrew, Reuben, Alexandre, Kadara, Humam, Wistuba, Ignacio I., and Zhang, Jianjun

Published
2021
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15. MICA, a gene contributing strong susceptibility to ankylosing spondylitis

Author

Zhou, Xiaodong, Wang, Jiucun, Zou, Hejian, Ward, Michael M, Weisman, Michael H, Espitia, Maribel G, Xiao, Xiangjun, Petersdorf, Effie, Mignot, Emmanuel, Martin, Javier, Gensler, Lianne S, Scheet, Paul, and Reveille, John D

Subjects
Biomedical and Clinical Sciences, Immunology, Prevention, Autoimmune Disease, Human Genome, Arthritis, Genetics, Aetiology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Adult, Asian, Cohort Studies, Female, Genetic Markers, Genetic Predisposition to Disease, HLA-B Antigens, Histocompatibility Antigens Class I, Humans, Linkage Disequilibrium, Male, Middle Aged, Risk Factors, Spondylitis, Ankylosing, United States, White People, Ankylosing Spondylitis, Gene Polymorphism, Inflammation, Clinical Sciences, Public Health and Health Services, Arthritis & Rheumatology, Clinical sciences
Abstract

ObjectiveThe human major histocompatibility complex class I chain-related gene A (MICA) controls the immune process by balancing activities of  natural killer cells, γδ T cells and αβ CD8 T cells, and immunosuppressive CD4 T cells. MICA is located near HLA-B on chromosome 6. Recent genomewide association studies indicate that genes most strongly linked to ankylosing spondylitis (AS) susceptibility come from the region containing HLA-B and MICA. While HLA-B27 is a well-known risk genetic marker for AS, the potential effect of linkage disequilibrium (LD) shields any associations of genes around HLA-B with AS. The aim of this study was to investigate a novel independent genetic association of MICA to AS.MethodsWe examined 1543 AS patients and 1539 controls from two ethnic populations by sequencing MICA and genotyping HLA-B alleles. Initially, 1070 AS patients and 1003 controls of European ancestry were used as a discovery cohort, followed by a confirmation cohort of 473 Han Chinese AS patients and 536 controls. We performed a stratified analysis based on HLA-B27 carrier status. We also conducted logistic regression with a formal interaction term.ResultsSequencing of MICA identified that MICA*007:01 is a significant risk allele for AS in both Caucasian and Han Chinese populations, and that MICA*019 is a major risk allele in Chinese AS patients. Conditional analysis of MICA alleles on HLA-B27 that unshielded LD effect confirmed associations of the MICA alleles with AS.ConclusionsParallel with HLA-B27, MICA confers strong susceptibility to AS in US white and Han Chinese populations.

Published
2014

16. A unified test of linkage analysis and rare-variant association for analysis of pedigree sequence data

Author

Hu, Hao, Roach, Jared C, Coon, Hilary, Guthery, Stephen L, Voelkerding, Karl V, Margraf, Rebecca L, Durtschi, Jacob D, Tavtigian, Sean V, Shankaracharya, Wu, Wilfred, Scheet, Paul, Wang, Shuoguo, Xing, Jinchuan, Glusman, Gustavo, Hubley, Robert, Li, Hong, Garg, Vidu, Moore, Barry, Hood, Leroy, Galas, David J, Srivastava, Deepak, Reese, Martin G, Jorde, Lynn B, Yandell, Mark, and Huff, Chad D

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Generic health relevance, Base Sequence, Chromosome Mapping, DNA, DNA Mutational Analysis, Genetic Linkage, Genetic Markers, Genetic Variation, High-Throughput Nucleotide Sequencing, Molecular Sequence Data, Pedigree
Abstract

High-throughput sequencing of related individuals has become an important tool for studying human disease. However, owing to technical complexity and lack of available tools, most pedigree-based sequencing studies rely on an ad hoc combination of suboptimal analyses. Here we present pedigree-VAAST (pVAAST), a disease-gene identification tool designed for high-throughput sequence data in pedigrees. pVAAST uses a sequence-based model to perform variant and gene-based linkage analysis. Linkage information is then combined with functional prediction and rare variant case-control association information in a unified statistical framework. pVAAST outperformed linkage and rare-variant association tests in simulations and identified disease-causing genes from whole-genome sequence data in three human pedigrees with dominant, recessive and de novo inheritance patterns. The approach is robust to incomplete penetrance and locus heterogeneity and is applicable to a wide variety of genetic traits. pVAAST maintains high power across studies of monogenic, high-penetrance phenotypes in a single pedigree to highly polygenic, common phenotypes involving hundreds of pedigrees.

Published
2014

17. Somatic mutation load of estrogen receptor-positive breast tumors predicts overall survival: an analysis of genome sequence data

Author

Haricharan, Svasti, Bainbridge, Matthew N, Scheet, Paul, and Brown, Powel H

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Human Genome, Genetic Testing, Cancer, Biotechnology, Breast Cancer, Genetics, 2.1 Biological and endogenous factors, Aetiology, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, Good Health and Well Being, Adult, Aged, Biomarkers, Tumor, Breast Neoplasms, Computational Biology, DNA Damage, DNA Repair, Databases, Nucleic Acid, Female, Genetic Association Studies, Genomics, Humans, Middle Aged, Mutation, Neoplasm Metastasis, Neoplasm Staging, Prognosis, Proportional Hazards Models, Receptors, Estrogen, Tumor Burden, Clinical Sciences, Oncology & Carcinogenesis, Clinical sciences, Oncology and carcinogenesis
Abstract

Breast cancer is one of the most commonly diagnosed cancers in women. While there are several effective therapies for breast cancer and important single gene prognostic/predictive markers, more than 40,000 women die from this disease every year. The increasing availability of large-scale genomic datasets provides opportunities for identifying factors that influence breast cancer survival in smaller, well-defined subsets. The purpose of this study was to investigate the genomic landscape of various breast cancer subtypes and its potential associations with clinical outcomes. We used statistical analysis of sequence data generated by the Cancer Genome Atlas initiative including somatic mutation load (SML) analysis, Kaplan-Meier survival curves, gene mutational frequency, and mutational enrichment evaluation to study the genomic landscape of breast cancer. We show that ER(+), but not ER(-), tumors with high SML associate with poor overall survival (HR = 2.02). Further, these high mutation load tumors are enriched for coincident mutations in both DNA damage repair and ER signature genes. While it is known that somatic mutations in specific genes affect breast cancer survival, this study is the first to identify that SML may constitute an important global signature for a subset of ER(+) tumors prone to high mortality. Moreover, although somatic mutations in individual DNA damage genes affect clinical outcome, our results indicate that coincident mutations in DNA damage response and signature ER genes may prove more informative for ER(+) breast cancer survival. Next generation sequencing may prove an essential tool for identifying pathways underlying poor outcomes and for tailoring therapeutic strategies.

Published
2014

18. Novel Susceptibility Variants at 10p12.31-12.2 for Childhood Acute Lymphoblastic Leukemia in Ethnically Diverse Populations

Author

Xu, Heng, Yang, Wenjian, Perez-Andreu, Virginia, Devidas, Meenakshi, Fan, Yiping, Cheng, Cheng, Pei, Deqing, Scheet, Paul, Burchard, Esteban González, Eng, Celeste, Huntsman, Scott, Torgerson, Dara G, Dean, Michael, Winick, Naomi J, Martin, Paul L, Camitta, Bruce M, Bowman, W Paul, Willman, Cheryl L, Carroll, William L, Mullighan, Charles G, Bhojwani, Deepa, Hunger, Stephen P, Pui, Ching-Hon, Evans, William E, Relling, Mary V, Loh, Mignon L, and Yang, Jun J

Subjects
Hematology, Rare Diseases, Cancer, Human Genome, Pediatric Cancer, Pediatric, Prevention, Childhood Leukemia, Clinical Research, Genetics, Aetiology, 2.1 Biological and endogenous factors, Adolescent, African Americans, CCAAT-Enhancer-Binding Proteins, Child, Child, Preschool, Chromosomes, Human, Pair 10, Chromosomes, Human, Pair 14, Chromosomes, Human, Pair 7, DNA-Binding Proteins, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Hispanic or Latino, Humans, Ikaros Transcription Factor, Logistic Models, Male, Mitogen-Activated Protein Kinase 7, Neoplasm Proteins, Phosphotransferases (Alcohol Group Acceptor), Polymorphism, Single Nucleotide, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Risk Assessment, Risk Factors, Transcription Factors, Whites, White People, Black or African American, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

BackgroundAcute lymphoblastic leukemia (ALL) is the most common cancer in children and the incidence of ALL varies by ethnicity. Although accumulating evidence indicates inherited predisposition to ALL, the genetic basis of ALL susceptibility in diverse ancestry has not been comprehensively examined.MethodsWe performed a multiethnic genome-wide association study in 1605 children with ALL and 6661 control subjects after adjusting for population structure, with validation in three replication series of 845 case subjects and 4316 control subjects. Association was tested by two-sided logistic regression.ResultsA novel ALL susceptibility locus at 10p12.31-12.2 (BMI1-PIP4K2A, rs7088318, P = 1.1 × 10(-11)) was identified in the genome-wide association study, with independent replication in European Americans, African Americans, and Hispanic Americans (P = .001, .009, and .04, respectively). Association was also validated at four known ALL susceptibility loci: ARID5B, IKZF1, CEBPE, and CDKN2A/2B. Associations at ARID5B, IKZF1, and BMI1-PIP4K2A variants were consistent across ethnicity, with multiple independent signals at IKZF1 and BMI1-PIP4K2A loci. The frequency of ARID5B and BMI1-PIP4K2A variants differed by ethnicity, in parallel with ethnic differences in ALL incidence. Suggestive evidence for modifying effects of age on genetic predisposition to ALL was also observed. ARID5B, IKZF1, CEBPE, and BMI1-PIP4K2A variants cumulatively conferred strong predisposition to ALL, with children carrying six to eight copies of risk alleles at a ninefold (95% confidence interval = 6.9 to 11.8) higher ALL risk relative to those carrying zero to one risk allele at these four single nucleotide polymorphisms.ConclusionsThese findings indicate strong associations between inherited genetic variation and ALL susceptibility in children and shed new light on ALL molecular etiology in diverse ancestry.

Published
2013

19. Multiomics profiling of primary lung cancers and distant metastases reveals immunosuppression as a common characteristic of tumor cells with metastatic plasticity

Author

Lee, Won-Chul, Reuben, Alexandre, Hu, Xin, McGranahan, Nicholas, Chen, Runzhe, Jalali, Ali, Negrao, Marcelo V., Hubert, Shawna M., Tang, Chad, Wu, Chia-Chin, Lucas, Anthony San, Roh, Whijae, Suda, Kenichi, Kim, Jihye, Tan, Aik-Choon, Peng, David H., Lu, Wei, Tang, Ximing, Chow, Chi-Wan, Fujimoto, Junya, Behrens, Carmen, Kalhor, Neda, Fukumura, Kazutaka, Coyle, Marcus, Thornton, Rebecca, Gumbs, Curtis, Li, Jun, Wu, Chang-Jiun, Little, Latasha, Roarty, Emily, Song, Xingzhi, Lee, J. Jack, Sulman, Erik P., Rao, Ganesh, Swisher, Stephen, Diao, Lixia, Wang, Jing, Heymach, John V., Huse, Jason T., Scheet, Paul, Wistuba, Ignacio I., Gibbons, Don L., Futreal, P. Andrew, Zhang, Jianhua, Gomez, Daniel, and Zhang, Jianjun

Published
2020
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20. Comprehensive T cell repertoire characterization of non-small cell lung cancer

Author

Reuben, Alexandre, Zhang, Jiexin, Chiou, Shin-Heng, Gittelman, Rachel M., Li, Jun, Lee, Won-Chul, Fujimoto, Junya, Behrens, Carmen, Liu, Xiaoke, Wang, Feng, Quek, Kelly, Wang, Chunlin, Kheradmand, Farrah, Chen, Runzhe, Chow, Chi-Wan, Lin, Heather, Bernatchez, Chantale, Jalali, Ali, Hu, Xin, Wu, Chang-Jiun, Eterovic, Agda Karina, Parra, Edwin Roger, Yusko, Erik, Emerson, Ryan, Benzeno, Sharon, Vignali, Marissa, Wu, Xifeng, Ye, Yuanqing, Little, Latasha D., Gumbs, Curtis, Mao, Xizeng, Song, Xingzhi, Tippen, Samantha, Thornton, Rebecca L., Cascone, Tina, Snyder, Alexandra, Wargo, Jennifer A., Herbst, Roy, Swisher, Stephen, Kadara, Humam, Moran, Cesar, Kalhor, Neda, Zhang, Jianhua, Scheet, Paul, Vaporciyan, Ara A., Sepesi, Boris, Gibbons, Don L., Robins, Harlan, Hwu, Patrick, Heymach, John V., Sharma, Padmanee, Allison, James P., Baladandayuthapani, Veera, Lee, Jack J., Davis, Mark M., Wistuba, Ignacio I., Futreal, P. Andrew, and Zhang, Jianjun

Published
2020
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22. Multi-region exome sequencing reveals genomic evolution from preneoplasia to lung adenocarcinoma

Author

Hu, Xin, Fujimoto, Junya, Ying, Lisha, Fukuoka, Junya, Ashizawa, Kazuto, Sun, Wenyong, Reuben, Alexandre, Chow, Chi-Wan, McGranahan, Nicholas, Chen, Runzhe, Hu, Jinlin, Godoy, Myrna C., Tabata, Kazuhiro, Kuroda, Kishio, Shi, Lei, Li, Jun, Behrens, Carmen, Parra, Edwin Roger, Little, Latasha D., Gumbs, Curtis, Mao, Xizeng, Song, Xingzhi, Tippen, Samantha, Thornton, Rebecca L., Kadara, Humam, Scheet, Paul, Roarty, Emily, Ostrin, Edwin Justin, Wang, Xu, Carter, Brett W., Antonoff, Mara B., Zhang, Jianhua, Vaporciyan, Ara A., Pass, Harvey, Swisher, Stephen G., Heymach, John V., Lee, J. Jack, Wistuba, Ignacio I., Hong, Waun Ki, Futreal, P. Andrew, Su, Dan, and Zhang, Jianjun

Published
2019
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23. Covid-19 Vaccine Efficacy: Accuracy Assessment, Comparison, and Caveats.

Author

WENJIANG FU, JIENI LI, and SCHEET, PAUL A.

Subjects
VACCINE effectiveness, COVID-19 vaccines, VACCINE trials, VACCINE development
Abstract

Vaccine efficacy is a key index to evaluate vaccines in initial clinical trials during the development of vaccines. In particular, it plays a crucial role in authorizing Covid-19 vaccines. It has been reported that Covid-19 vaccine efficacy varies with a number of factors, including demographics of population, time after vaccine administration, and virus strains. By examining clinical trial data of three Covid-19 vaccine studies, we find that current approach to evaluating vaccines with an overall efficacy does not provide desired accuracy. It requires no time frame during which a candidate vaccine is evaluated, and is subject to misuse, resulting in potential misleading information and interpretation. In particular, we illustrate with clinical trial data that the variability of vaccine efficacy is underestimated. We demonstrate that a new method may help to address these caveats. It leads to accurate estimation of the variation of efficacy, provides useful information to define a reasonable time frame to evaluate vaccines, and avoids misuse of vaccine efficacy and misleading information. [ABSTRACT FROM AUTHOR]

Published
2024
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24. Abstract 113: An atlas of epithelial cell states and plasticity in lung adenocarcinoma

Author

Han, Guangchun, primary, Sinjab, Ansam, additional, Treekitkarnmongkol, Warapen, additional, Rahal, Zahraa, additional, Liu, Yuejiang, additional, Serrano, Alejandra G., additional, Feng, Jiping, additional, Liang, Ke, additional, Khan, Khaja, additional, Lu, Wei, additional, Hernandez, Sharia, additional, Cao, Xuanye, additional, Dai, Enyu, additional, Liu, Yunhe, additional, Pei, Guangsheng, additional, Hu, Jian, additional, Bolanos, Lorena I. Gomez, additional, Parra, Edwin R., additional, Cascone, Tina, additional, Sepesi, Boris, additional, Moghaddam, Seyed Javad, additional, Scheet, Paul, additional, Negrao, Marcelo V., additional, Heymach, John V., additional, Li, Mingyao, additional, Chen, Jichao, additional, Dubinett, Steven M., additional, Fujimoto, Junya, additional, Solis, Luisa M., additional, Wistuba, Ignacio I., additional, Stevenson, Christopher S., additional, Spira, Avrum, additional, Wang, Linghua, additional, and Kadara, Humam, additional

Published
2023
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25. Abstract 3507: Mosaic chromosomal alterations in blood across ancestries via whole-genome sequencing

Author

Jakubek, Yasminka A., primary, Zhou, Ying, additional, Stilp, Adrienne, additional, Bacon, Jason, additional, Wong, Justin, additional, Ozcan, Zuhal, additional, Arnett, Donna, additional, Barnes, Kathleen, additional, Bis, Josh, additional, Boerwinkle, Eric, additional, Carson, April, additional, Chasman, Daniel, additional, Cho, Michael, additional, Conomos, Matthew, additional, Cox, Nancy, additional, Doyle, Margaret, additional, Fornage, Myriam, additional, Guo, Xiuqing, additional, Kardia, Sharon, additional, Lewis, Joshua, additional, Loos, Ruth, additional, Ma, Xiaolong, additional, Machiela, Mitchell, additional, Mack, Taralynn, additional, Mathias, Rasika, additional, Mitchell, Braxton, additional, North, Kari, additional, Pankratz, Nathan, additional, Peyser, Patricia, additional, Preuss, Michael, additional, Psaty, Bruce, additional, Raffield, Laura, additional, Vasan, Ramachandran, additional, Redline, Susan, additional, Rich, Stephen, additional, Rotter, Jerome, additional, Silverman, Edwin, additional, Smith, Jennifer, additional, Taub, Margaret, additional, Yun, Jeong, additional, Li, Yun, additional, Desai, Pinkal, additional, Bick, Alexander, additional, Reiner, Alexander, additional, Scheet, Paul, additional, and Auer, Paul, additional

Published
2023
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26. Germline genetic variants and pediatric rhabdomyosarcoma outcomes: a report from the Children’s Oncology Group

Author

Martin-Giacalone, Bailey A, primary, Richard, Melissa A, additional, Scheurer, Michael E, additional, Khan, Javed, additional, Sok, Pagna, additional, Shetty, Priya B, additional, Chanock, Stephen J, additional, Li, Shengchao Alfred, additional, Yeager, Meredith, additional, Marquez-Do, Deborah A, additional, Barkauskas, Donald A, additional, Hall, David, additional, McEvoy, Matthew T, additional, Brown, Austin L, additional, Sabo, Aniko, additional, Scheet, Paul, additional, Huff, Chad D, additional, Skapek, Stephen X, additional, Hawkins, Douglas S, additional, Venkatramani, Rajkumar, additional, Mirabello, Lisa, additional, and Lupo, Philip J, additional

Published
2023
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27. Clinical Characteristics and Cause of Death Among Hospitalized Decedents With Cancer and COVID-19

Author

Reddy, Dereddi Raja, primary, Cuenca, John A., additional, Botdorf, Joshua, additional, Muthu, Mayoora, additional, Hanmandlu, Ankit, additional, Wegner, Robert, additional, Crommett, John, additional, Gutierrez, Cristina, additional, Rathi, Nisha, additional, Sajith, Bilja, additional, Knafl, Mark, additional, Abbas, Hussein A., additional, Woodman, Scott E., additional, Nates, Joseph L., additional, Aaroe, Ashley, additional, Aloia, Thomas A., additional, Andrews, Lee, additional, Badami, Kiran K., additional, Baganz, Janna A., additional, Bajwa, Pratibha, additional, Baker, Lori R., additional, Barbosa, Gregory R., additional, Beird, Hannah C., additional, Bourgeois, Matt, additional, Brock, Kristy, additional, Burton, Elizabeth M., additional, Cata, Juan, additional, Chung, Caroline, additional, Cutherell, Michael, additional, Cyr, Pierre B., additional, Dabaja, Bouthaina, additional, Dagher, Hiba, additional, Daniels, Kevin M., additional, Domask, Mary, additional, Draetta, Giulio, additional, Fisher, Sarah, additional, French, Katy Elizabeth, additional, Futreal, Andrew, additional, Gaeta, Maria, additional, Gibbons, Christopher, additional, Godoy, Myrna, additional, Goldstein, Drew, additional, Gunther, Jillian, additional, Hernandez, Cristhiam, additional, Hutcheson, Kate, additional, Jaffray, David, additional, Jin, Jeff, additional, John, Teny Matthew, additional, Kell, Trey, additional, Kothari, Anai, additional, Kwan, Rayson C., additional, Lee, J. Jack, additional, Liao, Yue, additional, Litton, Jennifer, additional, Liu, Alex, additional, McEnery, Kevin W., additional, McGuire, Mary, additional, Musunuru, Tego, additional, Owen, Craig S., additional, Padmakumar, Priyadharshini, additional, Page, Melody, additional, Palaskas, Nicholas, additional, Patel, Jay J., additional, Prabhakaran, Sabitha, additional, Ravi, Vinod, additional, Russell, Ludivine, additional, Scheet, Paul A., additional, Schmidt, Stephanie, additional, Shaw, Kenna R., additional, Shete, Sanjay, additional, Shoenthal, Daniel P., additional, Stoltenberg, Lessley J., additional, Subbiah, Ishwaria, additional, Suitor, Chuck, additional, Tawbi, Hussein, additional, Thompson, Phillip, additional, Turin, Anastasia, additional, Unni, Samir, additional, Vicknamparampil, Benju, additional, Weber, Max C., additional, Weinstein, John, additional, Williams, Zoe, additional, Wozny, Mark C., additional, Wu, Carol, additional, Wu, Jia, additional, Yao, James C., additional, Young, Chingyi, additional, Yu, Emily, additional, and Zatorski, Steven, additional

Published
2023
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28. Mosaic chromosomal alterations in blood across ancestries using whole-genome sequencing

Author

Jakubek, Yasminka A., Zhou, Ying, Stilp, Adrienne, Bacon, Jason, Wong, Justin W., Ozcan, Zuhal, Arnett, Donna, Barnes, Kathleen, Bis, Joshua C., Boerwinkle, Eric, Brody, Jennifer A., Carson, April P., Chasman, Daniel I., Chen, Jiawen, Cho, Michael, Conomos, Matthew P., Cox, Nancy, Doyle, Margaret F., Fornage, Myriam, Guo, Xiuqing, Kardia, Sharon L.R., Lewis, Joshua P., Loos, Ruth J.F., Ma, Xiaolong, Machiela, Mitchell J., Mack, Taralynn M., Mathias, Rasika A., Mitchell, Braxton D., Mychaleckyj, Josyf C., North, Kari, Pankratz, Nathan, Peyser, Patricia A., Preuss, Michael H., Psaty, Bruce, Raffield, Laura M., Vasan, Ramachandran S., Redline, Susan, Rich, Stephen S., Rotter, Jerome I., Silverman, Edwin K., Smith, Jennifer A., Smith, Aaron P., Taub, Margaret, Taylor, Kent D., Yun, Jeong, Li, Yun, Desai, Pinkal, Bick, Alexander G., Reiner, Alexander P., Scheet, Paul, Auer, Paul L., Jakubek, Yasminka A., Zhou, Ying, Stilp, Adrienne, Bacon, Jason, Wong, Justin W., Ozcan, Zuhal, Arnett, Donna, Barnes, Kathleen, Bis, Joshua C., Boerwinkle, Eric, Brody, Jennifer A., Carson, April P., Chasman, Daniel I., Chen, Jiawen, Cho, Michael, Conomos, Matthew P., Cox, Nancy, Doyle, Margaret F., Fornage, Myriam, Guo, Xiuqing, Kardia, Sharon L.R., Lewis, Joshua P., Loos, Ruth J.F., Ma, Xiaolong, Machiela, Mitchell J., Mack, Taralynn M., Mathias, Rasika A., Mitchell, Braxton D., Mychaleckyj, Josyf C., North, Kari, Pankratz, Nathan, Peyser, Patricia A., Preuss, Michael H., Psaty, Bruce, Raffield, Laura M., Vasan, Ramachandran S., Redline, Susan, Rich, Stephen S., Rotter, Jerome I., Silverman, Edwin K., Smith, Jennifer A., Smith, Aaron P., Taub, Margaret, Taylor, Kent D., Yun, Jeong, Li, Yun, Desai, Pinkal, Bick, Alexander G., Reiner, Alexander P., Scheet, Paul, and Auer, Paul L.

Abstract

Megabase-scale mosaic chromosomal alterations (mCAs) in blood are prognostic markers for a host of human diseases. Here, to gain a better understanding of mCA rates in genetically diverse populations, we analyzed whole-genome sequencing data from 67,390 individuals from the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine program. We observed higher sensitivity with whole-genome sequencing data, compared with array-based data, in uncovering mCAs at low mutant cell fractions and found that individuals of European ancestry have the highest rates of autosomal mCAs and the lowest rates of chromosome X mCAs, compared with individuals of African or Hispanic ancestry. Although further studies in diverse populations will be needed to replicate our findings, we report three loci associated with loss of chromosome X, associations between autosomal mCAs and rare variants in DCPS, ADM17, PPP1R16B and TET2 and ancestry-specific variants in ATM and MPL with mCAs in cis.

Published
2023

29. Genetic risk factors for the development of osteonecrosis in children under age 10 treated for acute lymphoblastic leukemia

Author

Karol, Seth E., Mattano, Leonard A., Jr, Yang, Wenjian, Maloney, Kelly W., Smith, Colton, Liu, ChengCheng, Ramsey, Laura B., Fernandez, Christian A., Chang, Tamara Y., Neale, Geoffrey, Cheng, Cheng, Mardis, Elaine, Fulton, Robert, Scheet, Paul, San Lucas, F. Anthony, Larsen, Eric C., Loh, Mignon L., Raetz, Elizabeth A., Hunger, Stephen P., Devidas, Meenakshi, and Relling, Mary V.

Published
2016
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31. Genetics of glucocorticoid-associated osteonecrosis in children with acute lymphoblastic leukemia

Author

Karol, Seth E., Yang, Wenjian, Van Driest, Sara L., Chang, Tamara Y., Kaste, Sue, Bowton, Erica, Basford, Melissa, Bastarache, Lisa, Roden, Dan M., Denny, Joshua C., Larsen, Eric, Winick, Naomi, Carroll, William L., Cheng, Cheng, Pei, Deqing, Fernandez, Christian A., Liu, Chengcheng, Smith, Colton, Loh, Mignon L., Raetz, Elizabeth A., Hunger, Stephen P., Scheet, Paul, Jeha, Sima, Pui, Ching-Hon, Evans, William E., Devidas, Meenakshi, Mattano, Leonard A., Jr, and Relling, Mary V.

Published
2015
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32. NFAT5 and SLC4A10 Loci Associate with Plasma Osmolality

Author

Böger, Carsten A., Gorski, Mathias, McMahon, Gearoid M., Xu, Huichun, Chang, Yen-Pei C., van der Most, Peter J., Navis, Gerjan, Nolte, Ilja M., de Borst, Martin H., Zhang, Weihua, Lehne, Benjamin, Loh, Marie, Tan, Sian-Tsung, Boerwinkle, Eric, Grams, Morgan E., Sekula, Peggy, Li, Man, Wilmot, Beth, Moon, James G., Scheet, Paul, Cucca, Francesco, Xiao, Xiangjun, Lyytikäinen, Leo-Pekka, Delgado, Graciela, Grammer, Tanja B., Kleber, Marcus E., Sedaghat, Sanaz, Rivadeneira, Fernando, Corre, Tanguy, Kutalik, Zoltan, Bergmann, Sven, Nielson, Carrie M., Srikanth, Priya, Teumer, Alexander, Müller-Nurasyid, Martina, Brockhaus, Anne Catharina, Pfeufer, Arne, Rathmann, Wolfgang, Peters, Annette, Matsumoto, Martha, de Andrade, Mariza, Atkinson, Elizabeth J., Robinson-Cohen, Cassianne, de Boer, Ian H., Hwang, Shih-Jen, Heid, Iris M., Gögele, Martin, Concas, Maria Pina, Tanaka, Toshiko, Bandinelli, Stefania, Nalls, Mike A., Singleton, Andrew, Tajuddin, Salman M., Adeyemo, Adebowale, Zhou, Jie, Doumatey, Ayo, McWeeney, Shannon, Murabito, Joanne, Franceschini, Nora, Flessner, Michael, Shlipak, Michael, Wilson, James G., Chen, Guanjie, Rotimi, Charles N., Zonderman, Alan B., Evans, Michele K., Ferrucci, Luigi, Devuyst, Olivier, Pirastu, Mario, Shuldiner, Alan, Hicks, Andrew A., Pramstaller, Peter Paul, Kestenbaum, Bryan, Kardia, Sharon L.R., Turner, Stephen T., Study, LifeLines Cohort, Briske, Tamara Ellefson, Gieger, Christian, Strauch, Konstantin, Meisinger, Christa, Meitinger, Thomas, Völker, Uwe, Nauck, Matthias, Völzke, Henry, Vollenweider, Peter, Bochud, Murielle, Waeber, Gerard, Kähönen, Mika, Lehtimäki, Terho, März, Winfried, Dehghan, Abbas, Franco, Oscar H., Uitterlinden, Andre G., Hofman, Albert, Taylor, Herman A., Chambers, John C., Kooner, Jaspal S., Fox, Caroline S., Hitzemann, Robert, Orwoll, Eric S., Pattaro, Cristian, Schlessinger, David, Köttgen, Anna, Snieder, Harold, Parsa, Afshin, Cohen, David M., Alizadeh, Behrooz Z., Boezen, H. Marike, Franke, Lude, van der Harst, Pim, N., G., Rots, Marianne G., S., H., Swertz, Morris, Wolffenbuttel, Bruce H.R., and Wijmenga, Cisca

Published
2017
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33. Chronic exposure to waterpipe smoke elicits immunomodulatory and carcinogenic effects in the lung

Author

Hassane, Maya, primary, Rahal, Zahraa, additional, Karaoghlanian, Nareg, additional, Zhang, Jiexin, additional, Sinjab, Ansam, additional, Wong, Justin W., additional, Lu, Wei, additional, Scheet, Paul, additional, Lee, J. Jack., additional, Raso, Maria Gabriela, additional, Solis, Luisa M., additional, Fujimoto, Junya, additional, Chami, Hassan, additional, Shihadeh, Alan L., additional, and Kadara, Humam, additional

Published
2022
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34. Strengthening the reporting of genetic association studies (STREGA): an extension of the STROBE statement

Author

Little, Julian, Higgins, Julian P. T., Ioannidis, John P. A., Moher, David, Gagnon, France, von Elm, Erik, Khoury, Muin J., Cohen, Barbara, Davey-Smith, George, Grimshaw, Jeremy, Scheet, Paul, Gwinn, Marta, Williamson, Robin E., Zou, Guang Yong, Hutchings, Kim, Johnson, Candice Y., Tait, Valerie, Wiens, Miriam, Golding, Jean, van Duijn, Cornelia, McLaughlin, John, Paterson, Andrew, Wells, George, Fortier, Isabel, Freedman, Matthew, Zecevic, Maja, King, Richard, Infante-Rivard, Claire, Stewart, Alex, and Birkett, Nick

Published
2009

36. A whole-exome case-control association study to characterize the contribution of rare coding variation to pancreatic cancer risk

Author

Yu, Yao, primary, Chang, Kyle, additional, Chen, Jiun-Sheng, additional, Bohlender, Ryan J., additional, Fowler, Jerry, additional, Zhang, Di, additional, Huang, Maosheng, additional, Chang, Ping, additional, Li, Yanan, additional, Wong, Justin, additional, Wang, Huamin, additional, Gu, Jian, additional, Wu, Xifeng, additional, Schildkraut, Joellen, additional, Cannon-Albright, Lisa, additional, Ye, Yuanqing, additional, Zhao, Hua, additional, Hildebrandt, Michelle A.T., additional, Permuth, Jennifer B., additional, Li, Donghui, additional, Scheet, Paul, additional, and Huff, Chad, additional

Published
2021
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37. Clonal evolution in breast cancer revealed by single nucleus genome sequencing

Author

Wang, Yong, Waters, Jill, Leung, Marco L., Unruh, Anna, Roh, Whijae, Shi, Xiuqing, Chen, Ken, Scheet, Paul, Vattathil, Selina, Liang, Han, Multani, Asha, Zhang, Hong, Zhao, Rui, Michor, Franziska, Meric-Bernstam, Funda, and Navin, Nicholas E.

Subjects
Nucleotide sequencing -- Research, DNA sequencing -- Research, Genomes -- Research, Estrogen -- Research, Breast cancer -- Research -- Genetic aspects -- Development and progression -- Care and treatment -- Patient outcomes, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Sequencing studies of breast tumour cohorts have identified many prevalent mutations, but provide limited insight into the genomic diversity within tumours. Here we developed a whole-genome and exome single cell sequencing approach called nuc-seq that uses G2/M nuclei to achieve 91% mean coverage breadth. We applied this method to sequence single normal and tumour nuclei from an oestrogen-receptor-positive ([ER.sup.+]) breast cancer and a triple-negative ductal carcinoma. In parallel, we performed single nuclei copy number profiling. Our data show that aneuploid rearrangements occurred early in tumour evolution and remained highly stable as the tumour masses clonally expanded. In contrast, point mutations evolved gradually, generating extensive clonal diversity. Using targeted single-molecule sequencing, many of the diverse mutations were shown to occur at low frequencies (, Human breast cancers often display intratumour genomic heterogeneity (1-3). This clonal diversity confounds the clinical diagnosis and basic research of human cancers. Expression profiling has shown that breast cancers can [...]

Published
2014
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39. Combination of Sulindac and Bexarotene for Prevention of Intestinal Carcinogenesis in Familial Adenomatous Polyposis

Author

Bowen, Charles M., primary, Walter, Lewins, additional, Borras, Ester, additional, Wu, Wenhui, additional, Ozcan, Zuhal, additional, Chang, Kyle, additional, Bommi, Prashant V., additional, Taggart, Melissa W., additional, Thirumurthi, Selvi, additional, Lynch, Patrick M., additional, Reyes-Uribe, Laura, additional, Scheet, Paul A., additional, Sinha, Krishna M., additional, and Vilar, Eduardo, additional

Published
2021
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40. Rare Germline Variants in ATM Predispose to Prostate Cancer : A PRACTICAL Consortium Study

Author

PRACTICAL Consortium, Karlsson, Questa, Brook, Mark N, Dadaev, Tokhir, Wakerell, Sarah, Saunders, Edward J, Muir, Kenneth, Neal, David E, Giles, Graham G, MacInnis, Robert J, Thibodeau, Stephen N, McDonnell, Shannon K, Cannon-Albright, Lisa, Teixeira, Manuel R, Paulo, Paula, Cardoso, Marta, Huff, Chad, Li, Donghui, Yao, Yu, Scheet, Paul, Permuth, Jennifer B, Stanford, Janet L, Dai, James Y, Ostrander, Elaine A, Cussenot, Olivier, Cancel-Tassin, Géraldine, Hoegel, Josef, Herkommer, Kathleen, Schleutker, Johanna, Tammela, Teuvo L J, Rathinakannan, Venkat, Sipeky, Csilla, Wiklund, Fredrik, Grönberg, Henrik, Aly, Markus, Isaacs, William B, Dickinson, Jo L, FitzGerald, Liesel M, Chua, Melvin L K, Nguyen-Dumont, Tu, Schaid, Daniel J, Southey, Melissa C, Eeles, Rosalind A, Kote-Jarai, Zsofia, Tampere University, Department of Surgery, and Clinical Medicine

Subjects
Oncology, Male, medicine.medical_specialty, Urology, 030232 urology & nephrology, Disease, Ataxia Telangiectasia Mutated Proteins, urologic and male genital diseases, Targeted screening and therapy, Germline, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Internal medicine, Genetic predisposition, medicine, SNP, Humans, Radiology, Nuclear Medicine and imaging, Genetic Predisposition to Disease, Germ-Line Mutation, Variant Call Format, business.industry, Prostatic Neoplasms, Odds ratio, Priority Article, medicine.disease, 3126 Surgery, anesthesiology, intensive care, radiology, Confidence interval, ddc, 030220 oncology & carcinogenesis, Surgery, ATM gene mutations, business
Abstract

BACKGROUND: Germline ATM mutations are suggested to contribute to predisposition to prostate cancer (PrCa). Previous studies have had inadequate power to estimate variant effect sizes. OBJECTIVE: To precisely estimate the contribution of germline ATM mutations to PrCa risk. DESIGN, SETTING, AND PARTICIPANTS: We analysed next-generation sequencing data from 13 PRACTICAL study groups comprising 5560 cases and 3353 controls of European ancestry. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Variant Call Format files were harmonised, annotated for rare ATM variants, and classified as tier 1 (likely pathogenic) or tier 2 (potentially deleterious). Associations with overall PrCa risk and clinical subtypes were estimated. RESULTS AND LIMITATIONS: PrCa risk was higher in carriers of a tier 1 germline ATM variant, with an overall odds ratio (OR) of 4.4 (95% confidence interval [CI]: 2.0-9.5). There was also evidence that PrCa cases with younger age at diagnosis (

Published
2021

41. Genotype-Imputation Accuracy across Worldwide Human Populations

Author

Huang, Lucy, Li, Yun, Singleton, Andrew B., Hardy, John A., Abecasis, GoncAlo, Rosenberg, Noah A., and Scheet, Paul

Subjects
Aluminum compounds -- Analysis, Neurosciences -- Genetic aspects, Neurosciences -- Analysis, Genomics -- Genetic aspects, Genomics -- Analysis, Biological sciences
Abstract

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajhg.2009.01.013 Byline: Lucy Huang (1)(2), Yun Li (1), Andrew B. Singleton (3), John A. Hardy (4), Goncalo Abecasis (1), Noah A. Rosenberg (1)(2)(5), Paul Scheet (1)(6) Abstract: A current approach to mapping complex-disease-susceptibility loci in genome-wide association (GWA) studies involves leveraging the information in a reference database of dense genotype data. By modeling the patterns of linkage disequilibrium in a reference panel, genotypes not directly measured in the study samples can be imputed and tested for disease association. This imputation strategy has been successful for GWA studies in populations well represented by existing reference panels. We used genotypes at 513,008 autosomal single-nucleotide polymorphism (SNP) loci in 443 unrelated individuals from 29 worldwide populations to evaluate the 'portability' of the HapMap reference panels for imputation in studies of diverse populations. When a single HapMap panel was leveraged for imputation of randomly masked genotypes, European populations had the highest imputation accuracy, followed by populations from East Asia, Central and South Asia, the Americas, Oceania, the Middle East, and Africa. For each population, we identified 'optimal' mixtures of reference panels that maximized imputation accuracy, and we found that in most populations, mixtures including individuals from at least two HapMap panels produced the highest imputation accuracy. From a separate survey of additional SNPs typed in the same samples, we evaluated imputation accuracy in the scenario in which all genotypes at a given SNP position were unobserved and were imputed on the basis of data from a commercial 'SNP chip,' again finding that most populations benefited from the use of combinations of two or more HapMap reference panels. Our results can serve as a guide for selecting appropriate reference panels for imputation-based GWA analysis in diverse populations. Author Affiliation: (1) Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA (2) Center for Computational Medicine and Biology, University of Michigan, Ann Arbor, MI 48109, USA (3) Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA (4) Department of Molecular Neuroscience and Reta Lila Weston Institute of Neurological Studies, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK (5) Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA (6) Department of Epidemiology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA Article History: Received 11 September 2008; Revised 9 January 2009; Accepted 16 January 2009 Article Note: (miscellaneous) Published online: February 12, 2009

Published
2009
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42. The Transcriptomic Landscape of Mismatch Repair-Deficient Intestinal Stem Cells

Author

Bommi, Prashant V., primary, Bowen, Charles M., additional, Reyes-Uribe, Laura, additional, Wu, Wenhui, additional, Katayama, Hiroyuki, additional, Rocha, Pedro, additional, Parra, Edwin R., additional, Francisco-Cruz, Alejandro, additional, Ozcan, Zuhal, additional, Tosti, Elena, additional, Willis, Jason A., additional, Wu, Hong, additional, Taggart, Melissa W., additional, Burks, Jared K., additional, Lynch, Patrick M., additional, Edelmann, Winfried, additional, Scheet, Paul A., additional, Wistuba, Ignacio I., additional, Sinha, Krishna M., additional, Hanash, Samir M., additional, and Vilar, Eduardo, additional

Published
2021
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43. Single-Cell Expression Landscape of SARS-CoV-2 Receptor ACE2 and Host Proteases in Normal and Malignant Lung Tissues from Pulmonary Adenocarcinoma Patients

Author

Han, Guangchun, primary, Sinjab, Ansam, additional, Hara, Kieko, additional, Treekitkarnmongkol, Warapen, additional, Brennan, Patrick, additional, Chang, Kyle, additional, Bogatenkova, Elena, additional, Sanchez-Espiridion, Beatriz, additional, Behrens, Carmen, additional, Solis, Luisa M., additional, Gao, Boning, additional, Girard, Luc, additional, Zhang, Jianjun, additional, Sepesi, Boris, additional, Cascone, Tina, additional, Byers, Lauren A., additional, Gibbons, Don L., additional, Chen, Jichao, additional, Moghaddam, Seyed Javad, additional, Ostrin, Edwin J., additional, Scheet, Paul, additional, Fujimoto, Junya, additional, Shay, Jerry, additional, Heymach, John V., additional, Minna, John D., additional, Dubinett, Steven, additional, Wistuba, Ignacio I., additional, Stevenson, Christopher S., additional, Spira, Avrum E., additional, Wang, Linghua, additional, and Kadara, Humam, additional

Published
2021
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45. Defining the Comprehensive Genomic Landscapes of Pancreatic Ductal Adenocarcinoma Using Real-World Endoscopic Aspiration Samples

Author

Semaan, Alexander, primary, Bernard, Vincent, additional, Lee, Jaewon J., additional, Wong, Justin W., additional, Huang, Jonathan, additional, Swartzlander, Daniel B., additional, Stephens, Bret M., additional, Monberg, Maria E., additional, Weston, Brian R., additional, Bhutani, Manoop S., additional, Chang, Kyle, additional, Scheet, Paul A., additional, Maitra, Anirban, additional, Jakubek, Yasminka A., additional, and Guerrero, Paola A., additional

Published
2021
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46. Genotype, haplotype and copy-number variation in worldwide human populations

Author

Jakobsson, Mattias, Scholz, Sonja W., Scheet, Paul, Gibbs, J. Raphael, VanLiere, Jenna M., Fung, Hon-Chung, Szpiech, Zachary A., Degnan, James H., Wang, Kai, Guerreiro, Rita, Bras, Jose M., Schymick, Jennifer C., Hernandez, Dena G., Traynor, Bryan J., Simon-Sanchez, Javier, Matarin, Mar, Britton, Angela, van de Leemput, Joyce, Rafferty, Ian, Bucan, Maja, Cann, Howard M., Hardy, John A., Rosenberg, Noah A., and Singleton, Andrew B.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Genome-wide patterns of variation across individuals provide a powerful source of data for uncovering the history of migration, range expansion, and adaptation of the human species. However, high-resolution surveys of [...]

Published
2008

47. Additional file 3 of Multiomics profiling of primary lung cancers and distant metastases reveals immunosuppression as a common characteristic of tumor cells with metastatic plasticity

Author

Won-Chul Lee, Reuben, Alexandre, Hu, Xin, McGranahan, Nicholas, Runzhe Chen, Jalali, Ali, Negrao, Marcelo V., Hubert, Shawna M., Tang, Chad, Chia-Chin Wu, Lucas, Anthony San, Whijae Roh, Suda, Kenichi, Jihye Kim, Aik-Choon Tan, Peng, David H., Lu, Wei, Ximing Tang, Chi-Wan Chow, Fujimoto, Junya, Behrens, Carmen, Kalhor, Neda, Fukumura, Kazutaka, Coyle, Marcus, Thornton, Rebecca, Gumbs, Curtis, Li, Jun, Chang-Jiun Wu, Little, Latasha, Roarty, Emily, Xingzhi Song, J. Jack Lee, Sulman, Erik P., Rao, Ganesh, Swisher, Stephen, Lixia Diao, Wang, Jing, Heymach, John V., Huse, Jason T., Scheet, Paul, Wistuba, Ignacio I., Gibbons, Don L., P. Andrew Futreal, Jianhua Zhang, Gomez, Daniel, and Jianjun Zhang

Abstract

Additional file 3: Review history.

Published
2020
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48. Additional file 2 of Multiomics profiling of primary lung cancers and distant metastases reveals immunosuppression as a common characteristic of tumor cells with metastatic plasticity

Author

Won-Chul Lee, Reuben, Alexandre, Hu, Xin, McGranahan, Nicholas, Runzhe Chen, Jalali, Ali, Negrao, Marcelo V., Hubert, Shawna M., Tang, Chad, Chia-Chin Wu, Lucas, Anthony San, Whijae Roh, Suda, Kenichi, Jihye Kim, Aik-Choon Tan, Peng, David H., Lu, Wei, Ximing Tang, Chi-Wan Chow, Fujimoto, Junya, Behrens, Carmen, Kalhor, Neda, Fukumura, Kazutaka, Coyle, Marcus, Thornton, Rebecca, Gumbs, Curtis, Li, Jun, Chang-Jiun Wu, Little, Latasha, Roarty, Emily, Xingzhi Song, J. Jack Lee, Sulman, Erik P., Rao, Ganesh, Swisher, Stephen, Lixia Diao, Wang, Jing, Heymach, John V., Huse, Jason T., Scheet, Paul, Wistuba, Ignacio I., Gibbons, Don L., P. Andrew Futreal, Jianhua Zhang, Gomez, Daniel, and Jianjun Zhang

Abstract

Additional file 2: Supplementary Figs. S1-S22.

Published
2020
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