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1. Genetic architecture of telomere length in 462,666 UK Biobank whole-genome sequences

Author

Burren, Oliver S., Dhindsa, Ryan S., Deevi, Sri V. V., Wen, Sean, Nag, Abhishek, Mitchell, Jonathan, Hu, Fengyuan, Loesch, Douglas P., Smith, Katherine R., Razdan, Neetu, Olsson, Henric, Platt, Adam, Vitsios, Dimitrios, Wu, Qiang, Codd, Veryan, Nelson, Christopher P., Samani, Nilesh J., March, Ruth E., Wasilewski, Sebastian, Carss, Keren, Fabre, Margarete, Wang, Quanli, Pangalos, Menelas N., and Petrovski, Slavé

Published
2024
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3. Mendelian randomization supports bidirectional causality between telomere length and clonal hematopoiesis of indeterminate potential

Author

Nakao, Tetsushi, Bick, Alexander G, Taub, Margaret A, Zekavat, Seyedeh M, Uddin, Md M, Niroula, Abhishek, Carty, Cara L, Lane, John, Honigberg, Michael C, Weinstock, Joshua S, Pampana, Akhil, Gibson, Christopher J, Griffin, Gabriel K, Clarke, Shoa L, Bhattacharya, Romit, Assimes, Themistocles L, Emery, Leslie S, Stilp, Adrienne M, Wong, Quenna, Broome, Jai, Laurie, Cecelia A, Khan, Alyna T, Smith, Albert V, Blackwell, Thomas W, Codd, Veryan, Nelson, Christopher P, Yoneda, Zachary T, Peralta, Juan M, Bowden, Donald W, Irvin, Marguerite R, Boorgula, Meher, Zhao, Wei, Yanek, Lisa R, Wiggins, Kerri L, Hixson, James E, Gu, C Charles, Peloso, Gina M, Roden, Dan M, Reupena, Muagututi’a S, Hwu, Chii-Min, DeMeo, Dawn L, North, Kari E, Kelly, Shannon, Musani, Solomon K, Bis, Joshua C, Lloyd-Jones, Donald M, Johnsen, Jill M, Preuss, Michael, Tracy, Russell P, Peyser, Patricia A, Qiao, Dandi, Desai, Pinkal, Curran, Joanne E, Freedman, Barry I, Tiwari, Hemant K, Chavan, Sameer, Smith, Jennifer A, Smith, Nicholas L, Kelly, Tanika N, Hidalgo, Bertha, Cupples, L Adrienne, Weeks, Daniel E, Hawley, Nicola L, Minster, Ryan L, Deka, Ranjan, Naseri, Take T, de las Fuentes, Lisa, Raffield, Laura M, Morrison, Alanna C, Vries, Paul S, Ballantyne, Christie M, Kenny, Eimear E, Rich, Stephen S, Whitsel, Eric A, Cho, Michael H, Shoemaker, M Benjamin, Pace, Betty S, Blangero, John, Palmer, Nicholette D, Mitchell, Braxton D, Shuldiner, Alan R, Barnes, Kathleen C, Redline, Susan, Kardia, Sharon LR, Abecasis, Gonçalo R, Becker, Lewis C, Heckbert, Susan R, He, Jiang, Post, Wendy, Arnett, Donna K, Vasan, Ramachandran S, Darbar, Dawood, Weiss, Scott T, McGarvey, Stephen T, de Andrade, Mariza, Chen, Yii-Der Ida, Kaplan, Robert C, Meyers, Deborah A, Custer, Brian S, and Correa, Adolfo

Subjects
Cardiovascular, Genetics, Aging, Heart Disease, Heart Disease - Coronary Heart Disease, Human Genome, Atherosclerosis, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Samoan Obesity, Lifestyle and Genetic Adaptations Study (OLaGA) Group, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium
Abstract

Human genetic studies support an inverse causal relationship between leukocyte telomere length (LTL) and coronary artery disease (CAD), but directionally mixed effects for LTL and diverse malignancies. Clonal hematopoiesis of indeterminate potential (CHIP), characterized by expansion of hematopoietic cells bearing leukemogenic mutations, predisposes both hematologic malignancy and CAD. TERT (which encodes telomerase reverse transcriptase) is the most significantly associated germline locus for CHIP in genome-wide association studies. Here, we investigated the relationship between CHIP, LTL, and CAD in the Trans-Omics for Precision Medicine (TOPMed) program (n = 63,302) and UK Biobank (n = 47,080). Bidirectional Mendelian randomization studies were consistent with longer genetically imputed LTL increasing propensity to develop CHIP, but CHIP then, in turn, hastens to shorten measured LTL (mLTL). We also demonstrated evidence of modest mediation between CHIP and CAD by mLTL. Our data promote an understanding of potential causal relationships across CHIP and LTL toward prevention of CAD.

Published
2022

6. Germline thymidylate synthase deficiency impacts nucleotide metabolism and causes dyskeratosis congenita

Author

Tummala, Hemanth, primary, Walne, Amanda, additional, Buccafusca, Roberto, additional, Alnajar, Jenna, additional, Szabo, Anita, additional, Robinson, Peter, additional, McConkie-Rosell, Allyn, additional, Wilson, Meredith, additional, Crowley, Suzanne, additional, Kinsler, Veronica, additional, Ewins, Anna-Maria, additional, Madapura, Pradeepa M., additional, Patel, Manthan, additional, Pontikos, Nikolas, additional, Codd, Veryan, additional, Vulliamy, Tom, additional, and Dokal, Inderjeet, additional

Published
2024
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11. Polygenic basis and biomedical consequences of telomere length variation

Author

Codd, Veryan, Wang, Qingning, Allara, Elias, Musicha, Crispin, Kaptoge, Stephen, Stoma, Svetlana, Jiang, Tao, Hamby, Stephen E., Braund, Peter S., Bountziouka, Vasiliki, Budgeon, Charley A., Denniff, Matthew, Swinfield, Chloe, Papakonstantinou, Manolo, Sheth, Shilpi, Nanus, Dominika E., Warner, Sophie C., Wang, Minxian, Khera, Amit V., Eales, James, Ouwehand, Willem H., Thompson, John R., Di Angelantonio, Emanuele, Wood, Angela M., Butterworth, Adam S., Danesh, John N., Nelson, Christopher P., and Samani, Nilesh J.

Published
2021
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12. Large-Scale Analysis of the Association between Air Pollutants and Leucocyte Telomere Length in the UK Biobank

Author

Bountziouka, Vasiliki, Hansell, Anita L., Nelson, Christopher P., Codd, Veryan, and Sainani, Nilesh J.

Subjects
Telomeres -- Health aspects -- Physiological aspects, Air pollution -- Health aspects -- Physiological aspects, Leukocytes -- Physiological aspects -- Health aspects, Environmental issues, Health
Abstract

Introduction Shorter telomere length (TL) and air pollution are both associated with higher risk of aging-related diseases. (1,2) Oxidative stress may mediate the adverse effects of air pollution and also [...]

Published
2023
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14. Genetic Variation Associated with Longer Telomere Length Increases Risk of Chronic Lymphocytic Leukemia

Author

Ojha, Juhi, Codd, Veryan, Nelson, Christopher P, Samani, Nilesh J, Smirnov, Ivan V, Madsen, Nils R, Hansen, Helen M, de Smith, Adam J, Bracci, Paige M, Wiencke, John K, Wrensch, Margaret R, Wiemels, Joseph L, and Walsh, Kyle M

Subjects
Biomedical and Clinical Sciences, Prevention, Human Genome, Genetics, Clinical Research, Lymphoma, Cancer, Rare Diseases, Hematology, Adult, Aged, Biomarkers, Tumor, Case-Control Studies, Female, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Leukocytes, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, Telomere Homeostasis, ENGAGE Consortium Telomere Group, Medical and Health Sciences, Epidemiology, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundChronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world. Shorter mean telomere length in leukemic cells has been associated with more aggressive disease. Germline polymorphisms in telomere maintenance genes affect telomere length and may contribute to CLL susceptibility.MethodsWe collected genome-wide data from two groups of patients with CLL (N = 273) and two control populations (N = 5,725). In ancestry-adjusted case-control comparisons, we analyzed eight SNPs in genes definitively associated with inter-individual variation in leukocyte telomere length (LTL) in prior genome-wide association studies: ACYP2, TERC, NAF1, TERT, OBFC1, CTC1, ZNF208, and RTEL1 RESULTS: Three of the eight LTL-associated SNPs were associated with CLL risk at P < 0.05, including those near: TERC [OR, 1.46; 95% confidence interval (CI), 1.15-1.86; P = 1.8 × 10(-3)], TERT (OR = 1.23; 95% CI, 1.02-1.48; P = 0.030), and OBFC1 (OR, 1.36; 95% CI, 1.08-1.71; P = 9.6 × 10(-3)). Using a weighted linear combination of the eight LTL-associated SNPs, we observed that CLL patients were predisposed to longer LTL than controls in both case-control sets (P = 9.4 × 10(-4) and 0.032, respectively). CLL risk increased monotonically with increasing quintiles of the weighted linear combination.ConclusionsGenetic variants in TERC, TERT, and OBFC1 are associated with both longer LTL and increased CLL risk. Because the human CST complex competes with shelterin for telomeric DNA, future work should explore the role of OBFC1 and other CST complex genes in leukemogenesis.ImpactA genetic predisposition to longer telomere length is associated with an increased risk of CLL, suggesting that the role of telomere length in CLL etiology may be distinct from its role in disease progression. Cancer Epidemiol Biomarkers Prev; 25(7); 1043-9. ©2016 AACR.

Published
2016

15. Common genetic variants associated with telomere length confer risk for neuroblastoma and other childhood cancers

Author

Walsh, Kyle M, Whitehead, Todd P, de Smith, Adam J, Smirnov, Ivan V, Park, Minsun, Endicott, Alyson A, Francis, Stephen S, Codd, Veryan, Group, ENGAGE Consortium Telomere, Samani, Nilesh J, Metayer, Catherine, and Wiemels, Joseph L

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Human Genome, Rare Diseases, Pediatric Cancer, Genetics, Cancer, Orphan Drug, Childhood Leukemia, Cancer Genomics, Hematology, Prevention, Neuroblastoma, Neurosciences, Pediatric, 2.1 Biological and endogenous factors, Adolescent, Bone Neoplasms, Case-Control Studies, Child, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Leukocytes, Osteosarcoma, Polymorphism, Single Nucleotide, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Proteins, Telomere Homeostasis, Young Adult, ENGAGE Consortium Telomere Group, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

Aberrant telomere lengthening is an important feature of cancer cells in adults and children. In addition to somatic mutations, germline polymorphisms in telomere maintenance genes impact telomere length. Whether these telomere-associated polymorphisms affect risk of childhood malignancies remains largely unexplored. We collected genome-wide data from three groups with pediatric malignancies [neuroblastoma (N = 1516), acute lymphoblastic leukemia (ALL) (N = 958) and osteosarcoma (N = 660)] and three control populations (N = 6892). Using case-control comparisons, we analyzed eight single nucleotide polymorphisms (SNPs) in genes definitively associated with interindividual variation in leukocyte telomere length (LTL) in prior genome-wide association studies: ACYP2, TERC, NAF1, TERT, OBFC1, CTC1, ZNF208 and RTEL1 Six of these SNPs were associated (P < 0.05) with neuroblastoma risk, one with leukemia risk and one with osteosarcoma risk. The allele associated with longer LTL increased cancer risk for all these significantly associated SNPs. Using a weighted linear combination of the eight LTL-associated SNPs, we observed that neuroblastoma patients were predisposed to longer LTL than controls, with each standard deviation increase in genotypically estimated LTL associated with a 1.15-fold increased odds of neuroblastoma (95%CI = 1.09-1.22; P = 7.9×10(-7)). This effect was more pronounced in adolescent-onset neuroblastoma patients (OR = 1.46; 95%CI = 1.03-2.08). A one standard deviation increase in genotypically estimated LTL was more weakly associated with osteosarcoma risk (OR = 1.10; 95%CI = 1.01-1.19; P = 0.017) and leukemia risk (OR = 1.07; 95%CI = 1.00-1.14; P = 0.044), specifically for leukemia patients who relapsed (OR = 1.19; 95%CI = 1.01-1.40; P = 0.043). These results indicate that genetic predisposition to longer LTL is a newly identified risk factor for neuroblastoma and potentially for other cancers of childhood.

Published
2016

16. Authors’ Response

Author

Bountziouka, Vasiliki, primary, Nelson, Christopher P., additional, Codd, Veryan, additional, and Samani, Nilesh J., additional

Published
2023
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17. Longer genotypically-estimated leukocyte telomere length is associated with increased adult glioma risk

Author

Walsh, Kyle M, Codd, Veryan, Rice, Terri, Nelson, Christopher P, Smirnov, Ivan V, McCoy, Lucie S, Hansen, Helen M, Elhauge, Edward, Ojha, Juhi, Francis, Stephen S, Madsen, Nils R, Bracci, Paige M, Pico, Alexander R, Molinaro, Annette M, Tihan, Tarik, Berger, Mitchel S, Chang, Susan M, Prados, Michael D, Jenkins, Robert B, Wiemels, Joseph L, Group, ENGAGE Consortium Telomere, Samani, Nilesh J, Wiencke, John K, and Wrensch, Margaret R

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Human Genome, Brain Cancer, Cancer, Rare Diseases, Brain Disorders, Genetics, Prevention, Cancer Genomics, Neurosciences, 2.1 Biological and endogenous factors, Generic health relevance, Adult, Brain Neoplasms, Case-Control Studies, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Glioma, Humans, Leukocytes, Male, Models, Statistical, Polymorphism, Single Nucleotide, Risk Factors, Telomere, single nucleotide polymorphism, telomerase, telomere, CST complex, glioma, ENGAGE Consortium Telomere Group, Oncology and carcinogenesis
Abstract

Telomere maintenance has emerged as an important molecular feature with impacts on adult glioma susceptibility and prognosis. Whether longer or shorter leukocyte telomere length (LTL) is associated with glioma risk remains elusive and is often confounded by the effects of age and patient treatment. We sought to determine if genotypically-estimated LTL is associated with glioma risk and if inherited single nucleotide polymorphisms (SNPs) that are associated with LTL are glioma risk factors. Using a Mendelian randomization approach, we assessed differences in genotypically-estimated relative LTL in two independent glioma case-control datasets from the UCSF Adult Glioma Study (652 patients and 3735 controls) and The Cancer Genome Atlas (478 non-overlapping patients and 2559 controls). LTL estimates were based on a weighted linear combination of subject genotype at eight SNPs, previously associated with LTL in the ENGAGE Consortium Telomere Project. Mean estimated LTL was 31bp (5.7%) longer in glioma patients than controls in discovery analyses (P = 7.82x10-8) and 27bp (5.0%) longer in glioma patients than controls in replication analyses (1.48x10-3). Glioma risk increased monotonically with each increasing septile of LTL (O.R.=1.12; P = 3.83x10-12). Four LTL-associated SNPs were significantly associated with glioma risk in pooled analyses, including those in the telomerase component genes TERC (O.R.=1.14; 95% C.I.=1.03-1.28) and TERT (O.R.=1.39; 95% C.I.=1.27-1.52), and those in the CST complex genes OBFC1 (O.R.=1.18; 95% C.I.=1.05-1.33) and CTC1 (O.R.=1.14; 95% C.I.=1.02-1.28). Future work is needed to characterize the role of the CST complex in gliomagenesis and further elucidate the complex balance between ageing, telomere length, and molecular carcinogenesis.

Published
2015

18. The transcriptional landscape of age in human peripheral blood.

Author

Peters, Marjolein J, Joehanes, Roby, Pilling, Luke C, Schurmann, Claudia, Conneely, Karen N, Powell, Joseph, Reinmaa, Eva, Sutphin, George L, Zhernakova, Alexandra, Schramm, Katharina, Wilson, Yana A, Kobes, Sayuko, Tukiainen, Taru, NABEC/UKBEC Consortium, Ramos, Yolande F, Göring, Harald HH, Fornage, Myriam, Liu, Yongmei, Gharib, Sina A, Stranger, Barbara E, De Jager, Philip L, Aviv, Abraham, Levy, Daniel, Murabito, Joanne M, Munson, Peter J, Huan, Tianxiao, Hofman, Albert, Uitterlinden, André G, Rivadeneira, Fernando, van Rooij, Jeroen, Stolk, Lisette, Broer, Linda, Verbiest, Michael MPJ, Jhamai, Mila, Arp, Pascal, Metspalu, Andres, Tserel, Liina, Milani, Lili, Samani, Nilesh J, Peterson, Pärt, Kasela, Silva, Codd, Veryan, Peters, Annette, Ward-Caviness, Cavin K, Herder, Christian, Waldenberger, Melanie, Roden, Michael, Singmann, Paula, Zeilinger, Sonja, Illig, Thomas, Homuth, Georg, Grabe, Hans-Jörgen, Völzke, Henry, Steil, Leif, Kocher, Thomas, Murray, Anna, Melzer, David, Yaghootkar, Hanieh, Bandinelli, Stefania, Moses, Eric K, Kent, Jack W, Curran, Joanne E, Johnson, Matthew P, Williams-Blangero, Sarah, Westra, Harm-Jan, McRae, Allan F, Smith, Jennifer A, Kardia, Sharon LR, Hovatta, Iiris, Perola, Markus, Ripatti, Samuli, Salomaa, Veikko, Henders, Anjali K, Martin, Nicholas G, Smith, Alicia K, Mehta, Divya, Binder, Elisabeth B, Nylocks, K Maria, Kennedy, Elizabeth M, Klengel, Torsten, Ding, Jingzhong, Suchy-Dicey, Astrid M, Enquobahrie, Daniel A, Brody, Jennifer, Rotter, Jerome I, Chen, Yii-Der I, Houwing-Duistermaat, Jeanine, Kloppenburg, Margreet, Slagboom, P Eline, Helmer, Quinta, den Hollander, Wouter, Bean, Shannon, Raj, Towfique, Bakhshi, Noman, Wang, Qiao Ping, Oyston, Lisa J, Psaty, Bruce M, Tracy, Russell P, Montgomery, Grant W, and Turner, Stephen T

Subjects
NABEC/UKBEC Consortium, Humans, Gene Expression Profiling, DNA Methylation, Aging, European Continental Ancestry Group, Transcriptome, Biomarkers
Abstract

Disease incidences increase with age, but the molecular characteristics of ageing that lead to increased disease susceptibility remain inadequately understood. Here we perform a whole-blood gene expression meta-analysis in 14,983 individuals of European ancestry (including replication) and identify 1,497 genes that are differentially expressed with chronological age. The age-associated genes do not harbor more age-associated CpG-methylation sites than other genes, but are instead enriched for the presence of potentially functional CpG-methylation sites in enhancer and insulator regions that associate with both chronological age and gene expression levels. We further used the gene expression profiles to calculate the 'transcriptomic age' of an individual, and show that differences between transcriptomic age and chronological age are associated with biological features linked to ageing, such as blood pressure, cholesterol levels, fasting glucose, and body mass index. The transcriptomic prediction model adds biological relevance and complements existing epigenetic prediction models, and can be used by others to calculate transcriptomic age in external cohorts.

Published
2015

19. Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility

Author

Landi, Maria Teresa, Bishop, D. Timothy, MacGregor, Stuart, Machiela, Mitchell J., Stratigos, Alexander J., Ghiorzo, Paola, Brossard, Myriam, Calista, Donato, Choi, Jiyeon, Fargnoli, Maria Concetta, Zhang, Tongwu, Rodolfo, Monica, Trower, Adam J., Menin, Chiara, Martinez, Jacobo, Hadjisavvas, Andreas, Song, Lei, Stefanaki, Irene, Scolyer, Richard, Yang, Rose, Goldstein, Alisa M., Potrony, Miriam, Kypreou, Katerina P., Pastorino, Lorenza, Queirolo, Paola, Pellegrini, Cristina, Cattaneo, Laura, Zawistowski, Matthew, Gimenez-Xavier, Pol, Rodriguez, Arantxa, Elefanti, Lisa, Manoukian, Siranoush, Rivoltini, Licia, Smith, Blair H., Loizidou, Maria A., Del Regno, Laura, Massi, Daniela, Mandala, Mario, Khosrotehrani, Kiarash, Akslen, Lars A., Amos, Christopher I., Andresen, Per A., Avril, Marie-Françoise, Azizi, Esther, Soyer, H. Peter, Bataille, Veronique, Dalmasso, Bruna, Bowdler, Lisa M., Burdon, Kathryn P., Chen, Wei V., Codd, Veryan, Craig, Jamie E., Dębniak, Tadeusz, Falchi, Mario, Fang, Shenying, Friedman, Eitan, Simi, Sarah, Galan, Pilar, Garcia-Casado, Zaida, Gillanders, Elizabeth M., Gordon, Scott, Green, Adele, Gruis, Nelleke A., Hansson, Johan, Harland, Mark, Harris, Jessica, Helsing, Per, Henders, Anjali, Hočevar, Marko, Höiom, Veronica, Hunter, David, Ingvar, Christian, Kumar, Rajiv, Lang, Julie, Lathrop, G. Mark, Lee, Jeffrey E., Li, Xin, Lubiński, Jan, Mackie, Rona M., Malt, Maryrose, Malvehy, Josep, McAloney, Kerrie, Mohamdi, Hamida, Molven, Anders, Moses, Eric K., Neale, Rachel E., Novaković, Srdjan, Nyholt, Dale R., Olsson, Håkan, Orr, Nicholas, Fritsche, Lars G., Puig-Butille, Joan Anton, Qureshi, Abrar A., Radford-Smith, Graham L., Randerson-Moor, Juliette, Requena, Celia, Rowe, Casey, Samani, Nilesh J., Sanna, Marianna, Schadendorf, Dirk, Schulze, Hans-Joachim, Simms, Lisa A., Smithers, Mark, Song, Fengju, Swerdlow, Anthony J., van der Stoep, Nienke, Kukutsch, Nicole A., Visconti, Alessia, Wallace, Leanne, Ward, Sarah V., Wheeler, Lawrie, Sturm, Richard A., Hutchinson, Amy, Jones, Kristine, Malasky, Michael, Vogt, Aurelie, Zhou, Weiyin, Pooley, Karen A., Elder, David E., Han, Jiali, Hicks, Belynda, Hayward, Nicholas K., Kanetsky, Peter A., Brummett, Chad, Montgomery, Grant W., Olsen, Catherine M., Hayward, Caroline, Dunning, Alison M., Martin, Nicholas G., Evangelou, Evangelos, Mann, Graham J., Long, Georgina, Pharoah, Paul D. P., Easton, Douglas F., Barrett, Jennifer H., Cust, Anne E., Abecasis, Goncalo, Duffy, David L., Whiteman, David C., Gogas, Helen, De Nicolo, Arcangela, Tucker, Margaret A., Newton-Bishop, Julia A., Peris, Ketty, Chanock, Stephen J., Demenais, Florence, Brown, Kevin M., Puig, Susana, Nagore, Eduardo, Shi, Jianxin, Iles, Mark M., and Law, Matthew H.

Published
2020
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20. ED-36INHERITED VARIANTS NEAR TERC AND TERT ARE ASSOCIATED WITH LONGER TELOMERES AND INCREASED GLIOMA RISK: GENOME-WIDE ASSOCIATION RESULTS FROM THE UCSF ADULT GLIOMA STUDY AND THE ENGAGE CONSORTIUM TELOMERE GROUP

Author

Walsh, Kyle, Codd, Veryan, Smirnov, Ivan, Rice, Terri, Decker, Paul, Hansen, Helen, Molinaro, Annette, Pekmezci, Melike, Tihan, Tarik, Berger, Mitchell, Chang, Susan, Prados, Michael, Lachance, Dan, O'Neill, Brian Patrick, van der Harst, Pim, Wiencke, John, Samani, Nilesh, Jenkins, Robert, and Wrensch, Margaret

Subjects
Brain Cancer, Cancer, Genetics, Human Genome, Prevention, Rare Diseases, Brain Disorders, Neurosciences, 2.1 Biological and endogenous factors, Aetiology, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Published
2014

21. INHERITED VARIANTS NEAR TERC AND TERT ARE ASSOCIATED WITH LONGER TELOMERES AND INCREASED GLIOMA RISK: GENOME-WIDE ASSOCIATION RESULTS FROM THE UCSF ADULT GLIOMA STUDY AND THE ENGAGE CONSORTIUM TELOMERE GROUP

Author

Walsh, Kyle, Codd, Veryan, Smirnov, Ivan, Rice, Terri, Decker, Paul, Hansen, Helen, Molinaro, Annette, Pekmezci, Melike, Tihan, Tarik, Berger, Mitchell, Chang, Susan, Prados, Michael, Lachance, Dan, O'Neill, Brian Patrick, van der Harst, Pim, Wiencke, John, Samani, Nilesh, Jenkins, Robert, Wrensch, Margaret, and Grp, ENGAGE Consortium Telomere

Subjects
Neurosciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Published
2014

22. Variants near TERT and TERC influencing telomere length are associated with high-grade glioma risk.

Author

Codd, Veryan, Rice, Terri, Decker, Paul, Hansen, Helen, Kollmeyer, Thomas, Kosel, Matthew, McCoy, Lucie, Bracci, Paige, Cabriga, Belinda, Zheng, Shichun, Pico, Alexander, Lachance, Daniel, ONeill, Brian, Sicotte, Hugues, Eckel-Passow, Jeanette, van der Harst, Pim, Samani, Nilesh, Jenkins, Robert, Prados, Michael, Berger, Mitchel, Wiemels, Joseph, Chang, Susan, Walsh, Kyle, Tihan, Tarik, Wiencke, John, Wrensch, Margaret, Molinaro, Annette, Pekmezci, Melike, and Smirnov, Ivan

Subjects
Adult, Case-Control Studies, Genome-Wide Association Study, Genotype, Glioma, Humans, Leukocytes, Neoplasm Grading, Polymorphism, Single Nucleotide, Prognosis, RNA, Risk Factors, Telomerase, Telomere
Abstract

Glioma, the most common central nervous system cancer in adults, has poor prognosis. Here we identify a new SNP associated with glioma risk, rs1920116 (near TERC), that reached genome-wide significance (Pcombined = 8.3 × 10(-9)) in a meta-analysis of genome-wide association studies (GWAS) of high-grade glioma and replication data (1,644 cases and 7,736 controls). This region has previously been associated with mean leukocyte telomere length (LTL). We therefore examined the relationship between LTL and both this new risk locus and other previously established risk loci for glioma using data from a recent GWAS of LTL (n = 37,684 individuals). Alleles associated with glioma risk near TERC and TERT were strongly associated with longer LTL (P = 5.5 × 10(-20) and 4.4 × 10(-19), respectively). In contrast, risk-associated alleles near RTEL1 were inconsistently associated with LTL, suggesting the presence of distinct causal alleles. No other risk loci for glioma were associated with LTL. The identification of risk alleles for glioma near TERC and TERT that also associate with telomere length implicates telomerase in gliomagenesis.

Published
2014

23. Variants near TERT and TERC influencing telomere length are associated with high-grade glioma risk

Author

Walsh, Kyle M, Codd, Veryan, Smirnov, Ivan V, Rice, Terri, Decker, Paul A, Hansen, Helen M, Kollmeyer, Thomas, Kosel, Matthew L, Molinaro, Annette M, McCoy, Lucie S, Bracci, Paige M, Cabriga, Belinda S, Pekmezci, Melike, Zheng, Shichun, Wiemels, Joseph L, Pico, Alexander R, Tihan, Tarik, Berger, Mitchell S, Chang, Susan M, Prados, Michael D, Lachance, Daniel H, O'Neill, Brian Patrick, Sicotte, Hugues, Eckel-Passow, Jeanette E, van der Harst, Pim, Wiencke, John K, Samani, Nilesh J, Jenkins, Robert B, and Wrensch, Margaret R

Subjects
Agricultural, Veterinary and Food Sciences, Biological Sciences, Bioinformatics and Computational Biology, Genetics, Agricultural Biotechnology, Cancer, Neurosciences, Brain Disorders, Brain Cancer, Rare Diseases, Prevention, Adult, Case-Control Studies, Genome-Wide Association Study, Genotype, Glioma, Humans, Leukocytes, Neoplasm Grading, Polymorphism, Single Nucleotide, Prognosis, RNA, Risk Factors, Telomerase, Telomere, ENGAGE Consortium Telomere Group, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Glioma, the most common central nervous system cancer in adults, has poor prognosis. Here we identify a new SNP associated with glioma risk, rs1920116 (near TERC), that reached genome-wide significance (Pcombined = 8.3 × 10(-9)) in a meta-analysis of genome-wide association studies (GWAS) of high-grade glioma and replication data (1,644 cases and 7,736 controls). This region has previously been associated with mean leukocyte telomere length (LTL). We therefore examined the relationship between LTL and both this new risk locus and other previously established risk loci for glioma using data from a recent GWAS of LTL (n = 37,684 individuals). Alleles associated with glioma risk near TERC and TERT were strongly associated with longer LTL (P = 5.5 × 10(-20) and 4.4 × 10(-19), respectively). In contrast, risk-associated alleles near RTEL1 were inconsistently associated with LTL, suggesting the presence of distinct causal alleles. No other risk loci for glioma were associated with LTL. The identification of risk alleles for glioma near TERC and TERT that also associate with telomere length implicates telomerase in gliomagenesis.

Published
2014

25. Genetic architecture of telomere length in 462,675 UK Biobank whole-genome sequences

Author

Burren, Oliver Simon, primary, Dhindsa, Ryan, additional, Deevi, Sri Vishnu Vardhan, additional, Wen, Sean, additional, Nag, Abhishek, additional, Mitchell, Jonathan, additional, Hu, Fengyuan, additional, Smith, Katherine Rose, additional, Razdan, Neetu, additional, Olsson, Henric, additional, Platt, Adam, additional, Codd, Veryan, additional, Nelson, Christopher, additional, Samani, Nilesh, additional, March, Ruth, additional, Wasilewski, Sebastian, additional, Carss, Keren, additional, Fabre, Margarete, additional, Wang, Quanli, additional, Pangalos, Menelas, additional, and Petrovski, Slave, additional

Published
2023
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26. Association of Longer Leukocyte Telomere Length With Cardiac Size, Function, and Heart Failure

Author

Aung, Nay, primary, Wang, Qingning, additional, van Duijvenboden, Stefan, additional, Burns, Richard, additional, Stoma, Svetlana, additional, Raisi-Estabragh, Zahra, additional, Ahmet, Selda, additional, Allara, Elias, additional, Wood, Angela, additional, Di Angelantonio, Emanuele, additional, Danesh, John, additional, Munroe, Patricia B., additional, Young, Alistair, additional, Harvey, Nicholas C., additional, Codd, Veryan, additional, Nelson, Christopher P., additional, Petersen, Steffen E., additional, and Samani, Nilesh J., additional

Published
2023
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27. Comparison of Telomere Length in Young and Master Endurance Runners and Sprinters.

Author

Nickels, Matt, Mastana, Sarabjit, Codd, Veryan, Denniff, Matthew, and Akam, Elizabeth

Subjects
TELOMERES, ENDURANCE sports training, RUNNING, LEUCOCYTES, OLDER athletes, RANDOMIZED controlled trials, DESCRIPTIVE statistics, STATISTICAL sampling, POLYMERASE chain reaction, ORAL mucosa, CELL lines, SPRINTING
Abstract

It is unclear how running modality influences telomere length (TL). This single laboratory visit study compared the TL of master sprinters and endurance runners with their young counterparts. The correlation between leukocyte and buccal cell TL in athletes was also explored. Participants consisted of 11 young controls, 11 young sprinters, 12 young endurance runners, 12 middle-aged controls, 11 master sprinters, and 12 master endurance runners. Blood and buccal samples were collected and randomized for analysis of TL by quantitative polymerase chain reaction. Young endurance runners displayed longer telomeres than master athletes (p <.05); however, these differences were not significant when controlled for covariates (p >.05). A positive correlation existed between leukocyte and buccal cell TL in athletes (r =.567, p <.001). In conclusion, young endurance runners possess longer telomeres than master endurance runners and sprinters, a consequence of lower body mass index and visceral fat. [ABSTRACT FROM AUTHOR]

Published
2022
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28. Common genetic variations in telomere length genes and lung cancer: a Mendelian randomisation study and its novel application in lung tumour transcriptome

Author

Cortez Cardoso Penha, Ricardo, primary, Smith-Byrne, Karl, additional, Atkins, Joshua R, additional, Haycock, Philip C, additional, Kar, Siddhartha, additional, Codd, Veryan, additional, Samani, Nilesh J, additional, Nelson, Christopher, additional, Milojevic, Maja, additional, Gabriel, Aurélie AG, additional, Amos, Christopher, additional, Brennan, Paul, additional, Hung, Rayjean J, additional, Kachuri, Linda, additional, and Mckay, James D, additional

Published
2023
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29. A comparative analysis of the circadian clock in Diptera

Author

Codd, Veryan

Subjects
595.77
Abstract

The circadian central oscillator of Drosophila melanogaster consists of at least two interlocked negative transcriptional feedback loops. This has been taken to be a general model for higher eukaryotes with the core components conserved but their regulation altered. The work presented here indicates that in Musca domestica, a dipteran closely related to Drosophila, one of these regulatory loops, involving PERIOD (PER) and TIMELESS (TIM), functions in a completely different manner. This study shows that in contrast to Drosophila, Musca PER remains constant in western studies in any lighting condition, whereas like Drosophila TIM cycles in both LD and DD and is constantly degraded in LL. In addition within the central brain immunostaining revealed that even in the small set of cells thought to contain the central pacemaker PER staining was restricted exclusively to the cytoplasm. However following the Drosophila model PER was observed to cycle in the cytoplasm of these cells. Although TIM co-localises with PER in these cells, unlike PER, TIM does become nuclear. This indicates that the negative feedback model illustrated by analysis of the Drosophila is inadequate to explain clock function in Musca. A putative Musca PER nuclear export sequence which functions in other species was tested in GFP constructs but not shown to be involved in altered localisation. In contrast in peripheral tissue such as photoreceptor cells both PER and TIM cycle and both proteins become nuclear late at night as in Drosophila. Stability of Musca PER in LL and an altered relationship between transgenic Musca PER and Drosophila DOUBLETIME indicates an altered relationship between PER and the DBT kinase that may be responsible for PER stability. Thus although it can be seen that a different model is required for other insect species how these proteins act remains to be elucidated.

Published
2003

31. Modifiable traits, healthy behaviours, and leukocyte telomere length: a population-based study in UK Biobank

Author

Bountziouka, Vasiliki, Musicha, Crispin, Allara, Elias, Kaptoge, Stephen, Wang, Qingning, Angelantonio, Emanuele Di, Butterworth, Adam S, Thompson, John R, Danesh, John N, Wood, Angela M, Nelson, Christopher P, Codd, Veryan, Samani, Nilesh J, Allara, Elias [0000-0002-1634-8330], Kaptoge, Stephen [0000-0002-1155-4872], Di Angelantonio, Emanuele [0000-0001-8776-6719], Butterworth, Adam [0000-0002-6915-9015], Danesh, John [0000-0003-1158-6791], Wood, Angela [0000-0002-7937-304X], and Apollo - University of Cambridge Repository

Subjects
Male, Health (social science), Health Status, Health Behavior, Coronary Artery Disease, Mendelian Randomization Analysis, Telomere, United Kingdom, Psychiatry and Mental health, Leukocytes, Humans, Female, Geriatrics and Gerontology, Family Practice, Biological Specimen Banks
Abstract

BACKGROUND: Telomere length is associated with risk of several age-related diseases and cancers. We aimed to investigate the extent to which telomere length might be modifiable through lifestyle and behaviour, and whether such modification has any clinical consequences. METHODS: In this population-based study, we included participants from UK Biobank who had leukocyte telomere length (LTL) measurement, ethnicity, and white blood cell count data. We investigated associations of LTL with 117 potentially modifiable traits, as well as two indices of healthy behaviours incorporating between them smoking, physical activity, diet, maintenance of a healthy bodyweight, and alcohol intake, using both available and imputed data. To help interpretation, associations were summarised as the number of equivalent years of age-related change in LTL by dividing the trait β coefficients with the age β coefficient. We used mendelian randomisation to test causality of selected associations. We investigated whether the associations of LTL with 22 diseases were modified by the number of healthy behaviours and the extent to which the associations of more healthy behaviours with greater life expectancy and lower risk of coronary artery disease might be mediated through LTL. FINDINGS: 422 797 participants were available for the analysis (227 620 [53·8%] were women and 400 036 [94·6%] were White). 71 traits showed significant (p

Published
2022

32. Supplementary Information from Genetic Variation Associated with Longer Telomere Length Increases Risk of Chronic Lymphocytic Leukemia

Author

Ojha, Juhi, primary, Codd, Veryan, primary, Nelson, Christopher P., primary, Samani, Nilesh J., primary, Smirnov, Ivan V., primary, Madsen, Nils R., primary, Hansen, Helen M., primary, de Smith, Adam J., primary, Bracci, Paige M., primary, Wiencke, John K., primary, Wrensch, Margaret R., primary, Wiemels, Joseph L., primary, and Walsh, Kyle M., primary

Published
2023
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33. Data from Genetic Variation Associated with Longer Telomere Length Increases Risk of Chronic Lymphocytic Leukemia

Author

Ojha, Juhi, primary, Codd, Veryan, primary, Nelson, Christopher P., primary, Samani, Nilesh J., primary, Smirnov, Ivan V., primary, Madsen, Nils R., primary, Hansen, Helen M., primary, de Smith, Adam J., primary, Bracci, Paige M., primary, Wiencke, John K., primary, Wrensch, Margaret R., primary, Wiemels, Joseph L., primary, and Walsh, Kyle M., primary

Published
2023
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34. Telomere length and brain imaging phenotypes in UK Biobank

Author

Topiwala, Anya, primary, Nichols, Thomas E., additional, Williams, Logan Z. J., additional, Robinson, Emma C., additional, Alfaro-Almagro, Fidel, additional, Taschler, Bernd, additional, Wang, Chaoyue, additional, Nelson, Christopher P., additional, Miller, Karla L., additional, Codd, Veryan, additional, Samani, Nilesh J., additional, and Smith, Stephen M., additional

Published
2023
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35. Serum testosterone and sex hormone–binding globulin are inversely associated with leucocyte telomere length in men: a cross-sectional analysis of the UK Biobank study

Author

Marriott, Ross J, primary, Murray, Kevin, additional, Budgeon, Charley A, additional, Codd, Veryan, additional, Hui, Jennie, additional, Arscott, Gillian M, additional, Beilby, John P, additional, Hankey, Graeme J, additional, Wittert, Gary A, additional, Wu, Frederick C W, additional, and Yeap, Bu B, additional

Published
2023
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36. Author response: Common genetic variations in telomere length genes and lung cancer: a Mendelian randomisation study and its novel application in lung tumour transcriptome

Author

Cortez Cardoso Penha, Ricardo, primary, Smith-Byrne, Karl, additional, Atkins, Joshua R, additional, Haycock, Philip C, additional, Kar, Siddhartha, additional, Codd, Veryan, additional, Samani, Nilesh J, additional, Nelson, Christopher, additional, Milojevic, Maja, additional, Gabriel, Aurélie AG, additional, Amos, Christopher, additional, Brennan, Paul, additional, Hung, Rayjean J, additional, Kachuri, Linda, additional, and Mckay, James D, additional

Published
2023
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37. Metabolomics reveals a link between homocysteine and lipid metabolism and leukocyte telomere length: the ENGAGE consortium

Author

van der Spek, Ashley, Broer, Linda, Draisma, Harmen H. M., Pool, René, Albrecht, Eva, Beekman, Marian, Mangino, Massimo, Raag, Mait, Nyholt, Dale R., Dharuri, Harish K., Codd, Veryan, Amin, Najaf, de Geus, Eco J. C., Deelen, Joris, Demirkan, Ayse, Yet, Idil, Fischer, Krista, Haller, Toomas, Henders, Anjali K., Isaacs, Aaron, Medland, Sarah E., Montgomery, Grant W., Mooijaart, Simon P., Strauch, Konstantin, Suchiman, H. Eka D., Vaarhorst, Anika A. M., van Heemst, Diana, Wang-Sattler, Rui, Whitfield, John B., Willemsen, Gonneke, Wright, Margaret J., Martin, Nicholas G., Samani, Nilesh J., Metspalu, Andres, Eline Slagboom, P., Spector, Tim D., Boomsma, Dorret I., van Duijn, Cornelia M., and Gieger, Christian

Published
2019
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39. Common genetic variations in telomere length genes and lung cancer

Author

Penha, Ricardo Cortez Cardoso, primary, Smith-Byrne, Karl, additional, Atkins, Joshua R, additional, Haycock, Philip, additional, Kar, Siddhartha, additional, Codd, Veryan, additional, Samani, Nilesh J, additional, Nelson, Christopher P, additional, Milojevic, Maja, additional, Gabriel, Aurélie AG, additional, Amos, Christopher, additional, Brennan, Paul, additional, Hung, Rayjean J, additional, Kachuri, Linda, additional, and McKay, James D, additional

Published
2022
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40. Association of adiponectin and leptin with relative telomere length in seven independent cohorts including 11,448 participants

Author

Broer, Linda, Raschenberger, Julia, Deelen, Joris, Mangino, Massimo, Codd, Veryan, Pietiläinen, Kirsi H., Albrecht, Eva, Amin, Najaf, Beekman, Marian, de Craen, Anton J. M., Gieger, Christian, Haun, Margot, Henneman, Peter, Herder, Christian, Hovatta, Iiris, Laser, Annika, Kedenko, Lyudmyla, Koenig, Wolfgang, Kollerits, Barbara, Moilanen, Eeva, Oostra, Ben A., Paulweber, Bernhard, Quaye, Lydia, Rissanen, Aila, Roden, Michael, Surakka, Ida, Valdes, Ana M., Vuolteenaho, Katriina, Thorand, Barbara, van Dijk, Ko Willems, Kaprio, Jaakko, Spector, Tim D., Slagboom, P. Eline, Samani, Nilesh J., Kronenberg, Florian, van Duijn, Cornelia M., and Ladwig, Karl-Heinz

Published
2014

42. Common genetic variations in telomere length genes and lung cancer: a Mendelian randomisation study and its novel application in lung tumour transcriptome.

Author

Cardoso Penha, Ricardo Cortez, Smith-Byrne, Karl, Atkins, Joshua R., Haycock, Philip C., Kar, Siddhartha, Codd, Veryan, Samani, Nilesh J., Nelson, Christopher, Milojevic, Maja, Gabriel, Aurélie A. G., Amos, Christopher, Brennan, Paul, Hung, Rayjean J., Kachuri, Linda, and Mckay, James D.

Published
2023
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43. Association of shorter leucocyte telomere length with risk of frailty

Author

Bountziouka, Vasiliki, Nelson, Christopher P, Codd, Veryan, Wang, Qingning, Musicha, Crispin, Allara, Elias, Kaptoge, Stephen, Di Angelantonio, Emanuele, Butterworth, Adam S, Thompson, John R, Curtis, Elizabeth M, Wood, Angela, Danesh, John, Harvey, Nicholas C, Cooper, Cyrus, Samani, Nilesh J, Allara, Elias [0000-0002-1634-8330], Kaptoge, Stephen [0000-0002-1155-4872], Di Angelantonio, Emanuele [0000-0001-8776-6719], Wood, Angela [0000-0002-7937-304X], Danesh, John [0000-0003-1158-6791], and Apollo - University of Cambridge Repository

Subjects
Adult, Male, Frailty, Biological age, UK biobank, Telomere, Leucocyte telomere length, Cross-Sectional Studies, Risk Factors, Physiology (medical), Leukocytes, Humans, Orthopedics and Sports Medicine, Female
Abstract

BACKGROUND: Frailty is a multidimensional syndrome of decline that affects multiple systems and predisposes to adverse health outcomes. Although chronological age is the major risk factor, inter-individual variation in risk is not fully understood. Leucocyte telomere length (LTL), a proposed marker of biological age, has been associated with risk of many diseases. We sought to determine whether LTL is associated with risk of frailty. METHODS: We utilized cross-sectional data from 441 781 UK Biobank participants (aged 40-69 years), with complete data on frailty indicators and LTL. Frailty was defined as the presence of at least three of five indicators: weaker grip strength, slower walking pace, weight loss in the past year, lower physical activity, and exhaustion in the past 2 weeks. LTL was measured using a validated qPCR method and reported as a ratio of the telomere repeat number (T) to a single-copy gene (S) (T/S ratio). Association of LTL with frailty was evaluated using adjusted (chronological age, sex, deprivation, smoking, alcohol intake, body mass index, and multimorbidity) multinomial and ordinal regression models, and results are presented as relative risk (RRR) or odds ratios (OR), respectively, alongside the 95% confidence interval (CI). Mendelian randomization (MR), using 131 genetic variants associated with LTL, was used to assess if the association of LTL with frailty was causal. RESULTS: Frail participants (4.6%) were older (median age difference (95% CI): 3 (2.5; 3.5) years, P = 2.73 × 10-33 ), more likely to be female (61%, P = 1.97 × 10-129 ), and had shorter LTL (-0.13SD vs. 0.03SD, P = 5.43 × 10-111 ) than non-frail. In adjusted analyses, both age and LTL were associated with frailty (RRR = 1.03 (95% CI: 1.02; 1.04) per year of older chronological age, P = 3.99 × 10-12 ; 1.10 (1.08; 1.11) per SD shorter LTL, P = 1.46 × 10-30 ). Within each age group (40-49, 50-59, 60-69 years), the prevalence of frailty was about 33% higher in participants with shorter (-2SD) versus longer telomeres (+2SD). MR analysis showed an association of LTL with frailty that was directionally consistent with the observational association, but not statistically significant (MR-Median: OR (95% CI): 1.08 (0.98; 1.19) per SD shorter LTL, P = 0.13). CONCLUSIONS: Inter-individual variation in LTL is associated with the risk of frailty independently of chronological age and other risk factors. Our findings provide evidence for an additional biological determinant of frailty., This research has been conducted using the UK Biobank Resource under Application Number 6077. Generation of the LTL measurements was funded by the UK Medical Research Council (MRC), Biotechnology and Biological Sciences Research Council and British Heart Foundation (BHF) through MRC grant MR/M012816/1.

Published
2022
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44. Association of shorter leucocyte telomere length with risk of frailty

Author

Bountziouka, Vasiliki, primary, Nelson, Christopher P., additional, Codd, Veryan, additional, Wang, Qingning, additional, Musicha, Crispin, additional, Allara, Elias, additional, Kaptoge, Stephen, additional, Di Angelantonio, Emanuele, additional, Butterworth, Adam S., additional, Thompson, John R., additional, Curtis, Elizabeth M., additional, Wood, Angela M., additional, Danesh, John N., additional, Harvey, Nicholas C., additional, Cooper, Cyrus, additional, and Samani, Nilesh J., additional

Published
2022
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46. Modifiable traits, healthy behaviours, and leucocyte telomere length

Author

Bountziouka, Vasiliki, primary, Musicha, Crispin, additional, Allara, Elias, additional, Kaptoge, Stephen, additional, Wang, Qingning, additional, Di Angelantonio, Emanuele, additional, Butterworth, Adam S, additional, Thompson, John R, additional, Danesh, John N, additional, Wood, Angela M, additional, Nelson, Christopher P, additional, Codd, Veryan, additional, and Samani, Nilesh J, additional

Published
2021
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47. Telomere Length and Risk of Incident Fracture and Arthroplasty: Findings From UK Biobank.

Author

Curtis, Elizabeth M., Codd, Veryan, Nelson, Christopher, D'Angelo, Stefania, Wang, Qingning, Allara, Elias, Kaptoge, Stephen, Matthews, Paul M., Tobias, Jonathan H., Danesh, John, Cooper, Cyrus, Samani, Nilesh J., and Harvey, Nicholas C.

Abstract

We investigated independent associations between telomere length and risk of fracture and arthroplasty in UK Biobank participants. Leukocyte telomere length (LTL) was measured in baseline samples using a validated polymerase chain reaction (PCR) method. We used, in men and women separately, Cox proportional hazards models to calculate the hazard ratio (HR) for incident fracture (any, osteoporotic) or arthroplasty (hip or knee) over 1,186,410 person‐years of follow‐up. Covariates included age, white cell count, ethnicity, smoking, alcohol, physical activity, and menopause (women). In further analyses we adjusted for either estimated bone mineral density (eBMD) from heel quantitative ultrasound, handgrip strength, gait speed, total fat mass (bioimpedance), or blood biomarkers, all measured at baseline (2006–2010). We studied 59,500 women and 51,895 men, mean ± standard deviation (SD) age 56.4 ± 8.0 and 57.0 ± 8.3 years, respectively. During follow‐up there were 5619 fractures; 5285 hip and 4261 knee arthroplasties. In confounder‐adjusted models, longer LTL was associated with reduced risk of incident knee arthroplasty in both men (HR/SD 0.93; 95% confidence interval [CI], 0.88–0.97) and women (0.92; 95% CI, 0.88–0.96), and hip arthroplasty in men (0.91; 95% CI, 0.87–0.95), but not women (0.98; 95% CI, 0.94–1.01). Longer LTL was weakly associated with reduced risk of any incident fracture in women (HR/SD 0.96; 95% CI, 0.93–1.00) with less evidence in men (0.98; 95% CI, 0.93–1.02). Associations with incident outcomes were not materially altered by adjustment for heel eBMD, grip strength, gait speed, fat mass, or blood biomarker measures. In this, the largest study to date, longer LTL was associated with lower risk of incident knee or hip arthroplasty, but only weakly associated with lower risk of fracture. The relative risks were low at a population level, but our findings suggest that common factors acting on the myeloid and musculoskeletal systems might influence later life musculoskeletal outcomes. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Published
2022
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50. Variation in human herpesvirus 6B telomeric integration, excision, and transmission between tissues and individuals

Author

Wood, Michael L, primary, Veal, Colin D, additional, Neumann, Rita, additional, Suárez, Nicolás M, additional, Nichols, Jenna, additional, Parker, Andrei J, additional, Martin, Diana, additional, Romaine, Simon PR, additional, Codd, Veryan, additional, Samani, Nilesh J, additional, Voors, Adriaan A, additional, Tomaszewski, Maciej, additional, Flamand, Louis, additional, Davison, Andrew J, additional, and Royle, Nicola J, additional

Published
2021
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