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Your search keyword '"Arvanitis, Marios"' showing total 4 results
Start Over Author "Arvanitis, Marios" Publisher escholarship, university of california
4 results on '"Arvanitis, Marios"'

1. Validation of human telomere length multi-ancestry meta-analysis association signals identifies POP5 and KBTBD6 as human telomere length regulation genes

Author

Keener, Rebecca, Chhetri, Surya B, Connelly, Carla J, Taub, Margaret A, Conomos, Matthew P, Weinstock, Joshua, Ni, Bohan, Strober, Benjamin, Aslibekyan, Stella, Auer, Paul L, Barwick, Lucas, Becker, Lewis C, Blangero, John, Bleecker, Eugene R, Brody, Jennifer A, Cade, Brian E, Celedon, Juan C, Chang, Yi-Cheng, Cupples, L Adrienne, Custer, Brian, Freedman, Barry I, Gladwin, Mark T, Heckbert, Susan R, Hou, Lifang, Irvin, Marguerite R, Isasi, Carmen R, Johnsen, Jill M, Kenny, Eimear E, Kooperberg, Charles, Minster, Ryan L, Naseri, Take, Viali, Satupa’itea, Nekhai, Sergei, Pankratz, Nathan, Peyser, Patricia A, Taylor, Kent D, Telen, Marilyn J, Wu, Baojun, Yanek, Lisa R, Yang, Ivana V, Albert, Christine, Arnett, Donna K, Ashley-Koch, Allison E, Barnes, Kathleen C, Bis, Joshua C, Blackwell, Thomas W, Boerwinkle, Eric, Burchard, Esteban G, Carson, April P, Chen, Zhanghua, Chen, Yii-Der Ida, Darbar, Dawood, de Andrade, Mariza, Ellinor, Patrick T, Fornage, Myriam, Gelb, Bruce D, Gilliland, Frank D, He, Jiang, Islam, Talat, Kaab, Stefan, Kardia, Sharon LR, Kelly, Shannon, Konkle, Barbara A, Kumar, Rajesh, Loos, Ruth JF, Martinez, Fernando D, McGarvey, Stephen T, Meyers, Deborah A, Mitchell, Braxton D, Montgomery, Courtney G, North, Kari E, Palmer, Nicholette D, Peralta, Juan M, Raby, Benjamin A, Redline, Susan, Rich, Stephen S, Roden, Dan, Rotter, Jerome I, Ruczinski, Ingo, Schwartz, David, Sciurba, Frank, Shoemaker, M Benjamin, Silverman, Edwin K, Sinner, Moritz F, Smith, Nicholas L, Smith, Albert V, Tiwari, Hemant K, Vasan, Ramachandran S, Weiss, Scott T, Williams, L Keoki, Zhang, Yingze, Ziv, Elad, Raffield, Laura M, Reiner, Alexander P, Arvanitis, Marios, Greider, Carol W, Mathias, Rasika A, and Battle, Alexis

Subjects
Biological Sciences, Genetics, Human Genome, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors, Generic health relevance, Humans, Genome-Wide Association Study, Telomere, K562 Cells, Telomere Homeostasis, Polymorphism, Single Nucleotide, Gene Expression Regulation, CRISPR-Cas Systems, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed Hematology and Hemostasis Working Group, TOPMed Structural Variation Working Group
Abstract

Genome-wide association studies (GWAS) have become well-powered to detect loci associated with telomere length. However, no prior work has validated genes nominated by GWAS to examine their role in telomere length regulation. We conducted a multi-ancestry meta-analysis of 211,369 individuals and identified five novel association signals. Enrichment analyses of chromatin state and cell-type heritability suggested that blood/immune cells are the most relevant cell type to examine telomere length association signals. We validated specific GWAS associations by overexpressing KBTBD6 or POP5 and demonstrated that both lengthened telomeres. CRISPR/Cas9 deletion of the predicted causal regions in K562 blood cells reduced expression of these genes, demonstrating that these loci are related to transcriptional regulation of KBTBD6 and POP5. Our results demonstrate the utility of telomere length GWAS in the identification of telomere length regulation mechanisms and validate KBTBD6 and POP5 as genes affecting telomere length regulation.

Published
2024

2. The functional impact of rare variation across the regulatory cascade

Author

Li, Taibo, Ferraro, Nicole, Strober, Benjamin J, Aguet, Francois, Kasela, Silva, Arvanitis, Marios, Ni, Bohan, Wiel, Laurens, Hershberg, Elliot, Ardlie, Kristin, Arking, Dan E, Beer, Rebecca L, Brody, Jennifer, Blackwell, Thomas W, Clish, Clary, Gabriel, Stacey, Gerszten, Robert, Guo, Xiuqing, Gupta, Namrata, Johnson, W Craig, Lappalainen, Tuuli, Lin, Henry J, Liu, Yongmei, Nickerson, Deborah A, Papanicolaou, George, Pritchard, Jonathan K, Qasba, Pankaj, Shojaie, Ali, Smith, Josh, Sotoodehnia, Nona, Taylor, Kent D, Tracy, Russell P, Van Den Berg, David, Wheeler, Matthew T, Rich, Stephen S, Rotter, Jerome I, Battle, Alexis, and Montgomery, Stephen B

Subjects
Biological Sciences, Health Sciences, Genetics, Brain Disorders, Human Genome, Biotechnology, Aging, 2.1 Biological and endogenous factors, 2.5 Research design and methodologies (aetiology), Generic health relevance, functional genomics, machine learning, methylome, multi-omics, proteome, rare variants, transcriptome
Abstract

Each human genome has tens of thousands of rare genetic variants; however, identifying impactful rare variants remains a major challenge. We demonstrate how use of personal multi-omics can enable identification of impactful rare variants by using the Multi-Ethnic Study of Atherosclerosis, which included several hundred individuals, with whole-genome sequencing, transcriptomes, methylomes, and proteomes collected across two time points, 10 years apart. We evaluated each multi-omics phenotype's ability to separately and jointly inform functional rare variation. By combining expression and protein data, we observed rare stop variants 62 times and rare frameshift variants 216 times as frequently as controls, compared to 13-27 times as frequently for expression or protein effects alone. We extended a Bayesian hierarchical model, "Watershed," to prioritize specific rare variants underlying multi-omics signals across the regulatory cascade. With this approach, we identified rare variants that exhibited large effect sizes on multiple complex traits including height, schizophrenia, and Alzheimer's disease.

Published
2023

3. Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed

Author

Taub, Margaret A, Conomos, Matthew P, Keener, Rebecca, Iyer, Kruthika R, Weinstock, Joshua S, Yanek, Lisa R, Lane, John, Miller-Fleming, Tyne W, Brody, Jennifer A, Raffield, Laura M, McHugh, Caitlin P, Jain, Deepti, Gogarten, Stephanie M, Laurie, Cecelia A, Keramati, Ali, Arvanitis, Marios, Smith, Albert V, Heavner, Benjamin, Barwick, Lucas, Becker, Lewis C, Bis, Joshua C, Blangero, John, Bleecker, Eugene R, Burchard, Esteban G, Celedón, Juan C, Chang, Yen Pei C, Custer, Brian, Darbar, Dawood, de las Fuentes, Lisa, DeMeo, Dawn L, Freedman, Barry I, Garrett, Melanie E, Gladwin, Mark T, Heckbert, Susan R, Hidalgo, Bertha A, Irvin, Marguerite R, Islam, Talat, Johnson, W Craig, Kaab, Stefan, Launer, Lenore, Lee, Jiwon, Liu, Simin, Moscati, Arden, North, Kari E, Peyser, Patricia A, Rafaels, Nicholas, Seidman, Christine, Weeks, Daniel E, Wen, Fayun, Wheeler, Marsha M, Williams, L Keoki, Yang, Ivana V, Zhao, Wei, Aslibekyan, Stella, Auer, Paul L, Bowden, Donald W, Cade, Brian E, Chen, Zhanghua, Cho, Michael H, Cupples, L Adrienne, Curran, Joanne E, Daya, Michelle, Deka, Ranjan, Eng, Celeste, Fingerlin, Tasha E, Guo, Xiuqing, Hou, Lifang, Hwang, Shih-Jen, Johnsen, Jill M, Kenny, Eimear E, Levin, Albert M, Liu, Chunyu, Minster, Ryan L, Naseri, Take, Nouraie, Mehdi, Reupena, Muagututi A Sefuiva, Sabino, Ester C, Smith, Jennifer A, Smith, Nicholas L, Lasky-Su, Jessica, Taylor, James G, Telen, Marilyn J, Tiwari, Hemant K, Tracy, Russell P, White, Marquitta J, Zhang, Yingze, Wiggins, Kerri L, Weiss, Scott T, Vasan, Ramachandran S, Taylor, Kent D, Sinner, Moritz F, Silverman, Edwin K, Shoemaker, M Benjamin, Sheu, Wayne H-H, Sciurba, Frank, Schwartz, David A, Rotter, Jerome I, Roden, Daniel, Redline, Susan, and Raby, Benjamin A

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Human Genome, Biotechnology, Aetiology, 2.1 Biological and endogenous factors, Generic health relevance, Good Health and Well Being, NHLBI CARE Network, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed Hematology and Hemostasis Working Group, TOPMed Structural Variation Working Group
Abstract

Genetic studies on telomere length are important for understanding age-related diseases. Prior GWAS for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally-diverse individuals (European, African, Asian and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n=109,122 individuals. We identified 59 sentinel variants (p-value

Published
2022

4. De novo mutations across 1,465 diverse genomes reveal mutational insights and reductions in the Amish founder population

Author

Kessler, Michael D, Loesch, Douglas P, Perry, James A, Heard-Costa, Nancy L, Taliun, Daniel, Cade, Brian E, Wang, Heming, Daya, Michelle, Ziniti, John, Datta, Soma, Celedón, Juan C, Soto-Quiros, Manuel E, Avila, Lydiana, Weiss, Scott T, Barnes, Kathleen, Redline, Susan S, Vasan, Ramachandran S, Johnson, Andrew D, Mathias, Rasika A, Hernandez, Ryan, Wilson, James G, Nickerson, Deborah A, Abecasis, Goncalo, Browning, Sharon R, Zöllner, Sebastian, O’Connell, Jeffrey R, Mitchell, Braxton D, Lung, and Blood Institute Trans-Omics for Precision Medicine Consortium National Heart, Group, TOPMed Population Genetics Working, O’Connor, Timothy D, Aalbers, Sanne, Abdalla, Moustafa, Abdul-Rahman, Omar, Abecasis, Gonçalo, Abhyankar, Avinash, Adrianto, Indra, Aguet, Francois, Akers, Rachel, Al-Tobasei, Rafet, Albert, Christine, Aldred, Micheala, Almasy, Laura, Almeida, Marcio, Alonso, Alvaro, Ament, Seth, Ampleford, Elizabeth, An, Ping, Anderson, Christopher D, Andersson, Charlotte, Anugu, Pramod, Appelbaum, Elizabeth, Ardlie, Kristin, Arking, Dan, Armasu, Sebastian M, Arnett, Donna K, Arruda, Heather, Arvanitis, Marios, Ashley-Koch, Allison, Ashrani, Aneel, Aslibekyan, Stella, Assimes, Tim, Atkinson, Elizabeth, Auer, Paul, Austin, Thomas R, Avery, Christy, Avila-Pacheco, Julian, Avillach, Paul, Aviv, Abraham, Avramopoulos, Dimitrios, Ballantyne, Christie, Balte, Pallavi, Bamshad, Michael, Bancks, Mike, Barnard, John, Barr, R Graham, Barron-Casella, Emily, Bartz, Traci, Barwick, Lucas, Basu, Saonli, Battle, Alexis, Baumann, Michael, Beame, David, Beaty, Terri, Beck, Gerald, Becker, Lewis, Becker, Diane, Beer, Rebecca, Begum, Ferdouse, Beiser, Alexa, Beitelshees, Amber, Benjamin, Emelia, Benos, Takis, Berk-Rauch, Hanna, Besich, Zachary M, Bezerra, Marcos, Bhatt, Surya, Bi, Wenjian, Bick, Alexander, and Bielak, Larry

Subjects
Biological Sciences, Genetics, Biotechnology, Human Genome, Precision Medicine, 2.1 Biological and endogenous factors, Good Health and Well Being, Adult, Amish, Cohort Studies, DNA Mutational Analysis, Female, Genetics, Population, Genome, Human, Heterozygote, Humans, Male, Mutation, Pedigree, Whole Genome Sequencing, Young Adult, National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed Population Genetics Working Group, de novo mutations, diversity, mutation rate, recombination
Abstract

De novo mutations (DNMs), or mutations that appear in an individual despite not being seen in their parents, are an important source of genetic variation whose impact is relevant to studies of human evolution, genetics, and disease. Utilizing high-coverage whole-genome sequencing data as part of the Trans-Omics for Precision Medicine (TOPMed) Program, we called 93,325 single-nucleotide DNMs across 1,465 trios from an array of diverse human populations, and used them to directly estimate and analyze DNM counts, rates, and spectra. We find a significant positive correlation between local recombination rate and local DNM rate, and that DNM rate explains a substantial portion (8.98 to 34.92%, depending on the model) of the genome-wide variation in population-level genetic variation from 41K unrelated TOPMed samples. Genome-wide heterozygosity does correlate with DNM rate, but only explains

Published
2020

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