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2. Genome-wide analyses characterize shared heritability among cancers and identify novel cancer susceptibility regions

Author

Lindström, Sara, Wang, Lu, Feng, Helian, Majumdar, Arunabha, Huo, Sijia, Macdonald, James, Harrison, Tabitha, Turman, Constance, Chen, Hongjie, Mancuso, Nicholas, Bammler, Theo, Consortium, Breast Cancer Association, Gallinger, Steve, Gruber, Stephen B, Gunter, Marc J, Le Marchand, Loic, Moreno, Victor, Offit, Kenneth, Study, Genetics And Epidemiology Of Colorectal Cancer Consortium Colorectal Transdisciplinary Study Colon Cancer Family Registry, De Vivo, Immaculata, O’Mara, Tracy A, Spurdle, Amanda B, Tomlinson, Ian, Consortium, Endometrial Cancer Association, Fitzgerald, Rebecca, Gharahkhani, Puya, Gockel, Ines, Jankowski, Janusz, Macgregor, Stuart, Schumacher, Johannes, Barnholtz-Sloan, Jill, Bondy, Melissa L, Houlston, Richard S, Jenkins, Robert B, Melin, Beatrice, Wrensch, Margaret, Brennan, Paul, Christiani, David C, Johansson, Mattias, Mckay, James, Aldrich, Melinda C, Amos, Christopher I, Landi, Maria Teresa, Tardon, Adonina, Consortium, International Lung Cancer, Bishop, D Timothy, Demenais, Florence, Goldstein, Alisa M, Iles, Mark M, Kanetsky, Peter A, Law, Matthew H, Consortium, Ovarian Cancer Association, Amundadottir, Laufey T, Stolzenberg-Solomon, Rachael, Wolpin, Brian M, Consortium, Pancreatic Cancer Cohort, Klein, Alison, Petersen, Gloria, Risch, Harvey, Consortium, The PRACTICAL Consortium Pancreatic Cancer Case-Control, Chanock, Stephen J, Purdue, Mark P, Scelo, Ghislaine, Pharoah, Paul, Kar, Siddhartha, Hung, Rayjean J, Pasaniuc, Bogdan, and Kraft, Peter

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Human Genome, Genetics, Digestive Diseases, Prevention, Clinical Research, Urologic Diseases, Cancer, Rare Diseases, Aetiology, 2.1 Biological and endogenous factors, Male, Humans, Genome-Wide Association Study, Genetic Predisposition to Disease, Neoplasms, Risk Factors, Transcriptome, Polymorphism, Single Nucleotide, Breast Cancer Association Consortium, Colorectal Transdisciplinary Study (CORECT), Colon Cancer Family Registry Study (CCFR), Genetics And Epidemiology Of Colorectal Cancer Consortium, Endometrial Cancer Association Consortium, International Lung Cancer Consortium, Ovarian Cancer Association Consortium, Pancreatic Cancer Cohort Consortium, Pancreatic Cancer Case-Control Consortium (Panc4), The PRACTICAL Consortium, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

BackgroundThe shared inherited genetic contribution to risk of different cancers is not fully known. In this study, we leverage results from 12 cancer genome-wide association studies (GWAS) to quantify pairwise genome-wide genetic correlations across cancers and identify novel cancer susceptibility loci.MethodsWe collected GWAS summary statistics for 12 solid cancers based on 376 759 participants with cancer and 532 864 participants without cancer of European ancestry. The included cancer types were breast, colorectal, endometrial, esophageal, glioma, head and neck, lung, melanoma, ovarian, pancreatic, prostate, and renal cancers. We conducted cross-cancer GWAS and transcriptome-wide association studies to discover novel cancer susceptibility loci. Finally, we assessed the extent of variant-specific pleiotropy among cancers at known and newly identified cancer susceptibility loci.ResultsWe observed widespread but modest genome-wide genetic correlations across cancers. In cross-cancer GWAS and transcriptome-wide association studies, we identified 15 novel cancer susceptibility loci. Additionally, we identified multiple variants at 77 distinct loci with strong evidence of being associated with at least 2 cancer types by testing for pleiotropy at known cancer susceptibility loci.ConclusionsOverall, these results suggest that some genetic risk variants are shared among cancers, though much of cancer heritability is cancer-specific and thus tissue-specific. The increase in statistical power associated with larger sample sizes in cross-disease analysis allows for the identification of novel susceptibility regions. Future studies incorporating data on multiple cancer types are likely to identify additional regions associated with the risk of multiple cancer types.

Published
2023

3. Discovery of genomic loci associated with sleep apnea risk through multi-trait GWAS analysis with snoring.

Author

Campos, Adrian, Ingold, Nathan, Huang, Yunru, Mitchell, Brittany, Kho, Pik-Fang, Han, Xikun, García-Marín, Luis, Ong, Jue-Sheng, Law, Matthew, Martin, Nicholas, Dong, Xianjun, Cuellar-Partida, Gabriel, MacGregor, Stuart, Aslibekyan, Stella, Rentería, Miguel, and Yokoyama, Jennifer

Subjects
GWAS, genetics, sleep apnea, snoring, Humans, Genome-Wide Association Study, Snoring, Phenotype, Sleep Apnea Syndromes, Genomics, Polymorphism, Single Nucleotide
Abstract

STUDY OBJECTIVES: Despite its association with severe health conditions, the etiology of sleep apnea (SA) remains understudied. This study sought to identify genetic variants robustly associated with SA risk. METHODS: We performed a genome-wide association study (GWAS) meta-analysis of SA across five cohorts (NTotal = 523 366), followed by a multi-trait analysis of GWAS (multi-trait analysis of genome-wide association summary statistics [MTAG]) to boost power, leveraging the high genetic correlation between SA and snoring. We then adjusted our results for the genetic effects of body mass index (BMI) using multi-trait-based conditional and joint analysis (mtCOJO) and sought replication of lead hits in a large cohort of participants from 23andMe, Inc (NTotal = 1 477 352; Ncases = 175 522). We also explored genetic correlations with other complex traits and performed a phenome-wide screen for causally associated phenotypes using the latent causal variable method. RESULTS: Our SA meta-analysis identified five independent variants with evidence of association beyond genome-wide significance. After adjustment for BMI, only one genome-wide significant variant was identified. MTAG analyses uncovered 49 significant independent loci associated with SA risk. Twenty-nine variants were replicated in the 23andMe GWAS adjusting for BMI. We observed genetic correlations with several complex traits, including multisite chronic pain, diabetes, eye disorders, high blood pressure, osteoarthritis, chronic obstructive pulmonary disease, and BMI-associated conditions. CONCLUSION: Our study uncovered multiple genetic loci associated with SA risk, thus increasing our understanding of the etiology of this condition and its relationship with other complex traits.

Published
2023

4. The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions

Author

Rahmioglu, Nilufer, Mortlock, Sally, Ghiasi, Marzieh, Møller, Peter L, Stefansdottir, Lilja, Galarneau, Geneviève, Turman, Constance, Danning, Rebecca, Law, Matthew H, Sapkota, Yadav, Christofidou, Paraskevi, Skarp, Sini, Giri, Ayush, Banasik, Karina, Krassowski, Michal, Lepamets, Maarja, Marciniak, Błażej, Nõukas, Margit, Perro, Danielle, Sliz, Eeva, Sobalska-Kwapis, Marta, Thorleifsson, Gudmar, Topbas-Selcuki, Nura F, Vitonis, Allison, Westergaard, David, Arnadottir, Ragnheidur, Burgdorf, Kristoffer S, Campbell, Archie, Cheuk, Cecilia SK, Clementi, Caterina, Cook, James, De Vivo, Immaculata, DiVasta, Amy, Dorien, O, Donoghue, Jacqueline F, Edwards, Todd, Fontanillas, Pierre, Fung, Jenny N, Geirsson, Reynir T, Girling, Jane E, Harkki, Paivi, Harris, Holly R, Healey, Martin, Heikinheimo, Oskari, Holdsworth-Carson, Sarah, Hostettler, Isabel C, Houlden, Henry, Houshdaran, Sahar, Irwin, Juan C, Jarvelin, Marjo-Riitta, Kamatani, Yoichiro, Kennedy, Stephen H, Kepka, Ewa, Kettunen, Johannes, Kubo, Michiaki, Kulig, Bartosz, Kurra, Venla, Laivuori, Hannele, Laufer, Marc R, Lindgren, Cecilia M, MacGregor, Stuart, Mangino, Massimo, Martin, Nicholas G, Matalliotaki, Charoula, Matalliotakis, Michail, Murray, Alison D, Ndungu, Anne, Nezhat, Camran, Olsen, Catherine M, Opoku-Anane, Jessica, Padmanabhan, Sandosh, Paranjpe, Manish, Peters, Maire, Polak, Grzegorz, Porteous, David J, Rabban, Joseph, Rexrode, Kathyrn M, Romanowicz, Hanna, Saare, Merli, Saavalainen, Liisu, Schork, Andrew J, Sen, Sushmita, Shafrir, Amy L, Siewierska-Górska, Anna, Słomka, Marcin, Smith, Blair H, Smolarz, Beata, Szaflik, Tomasz, Szyłło, Krzysztof, Takahashi, Atsushi, Terry, Kathryn L, Tomassetti, Carla, Treloar, Susan A, Vanhie, Arne, Vincent, Katy, Vo, Kim C, Werring, David J, Zeggini, Eleftheria, Zervou, Maria I, and Adachi, Sosuke

Subjects
Biological Sciences, Genetics, Contraception/Reproduction, Clinical Research, Endometriosis, Prevention, Pain Research, Chronic Pain, Infertility, 2.1 Biological and endogenous factors, Aetiology, Female, Humans, Genetic Predisposition to Disease, Genome-Wide Association Study, Pain, Comorbidity, DBDS Genomic Consortium, FinnGen Study, FinnGen Endometriosis Taskforce, Celmatix Research Team, 23andMe Research Team, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention.

Published
2023

7. Uncovering the complex relationship between balding, testosterone and skin cancers in men

Author

Ong, Jue-Sheng, Seviiri, Mathias, Dusingize, Jean Claude, Wu, Yeda, Han, Xikun, Shi, Jianxin, Olsen, Catherine M., Neale, Rachel E., Thompson, John F., Saw, Robyn P. M., Shannon, Kerwin F., Mann, Graham J., Martin, Nicholas G., Medland, Sarah E., Gordon, Scott D., Scolyer, Richard A., Long, Georgina V., Iles, Mark M., Landi, Maria Teresa, Whiteman, David C., MacGregor, Stuart, and Law, Matthew H.

Published
2023
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8. Long-term HIV care outcomes under universal HIV treatment guidelines: A retrospective cohort study in 25 countries

Author

Brazier, Ellen, Tymejczyk, Olga, Wools-Kaloustian, Kara, Jiamsakul, Awachana, Torres, Marco Tulio Luque, Lee, Jennifer S., Abuogi, Lisa, Khol, Vohith, Mejía Cordero, Fernando, Althoff, Keri N., Law, Matthew G., and Nash, Denis

Subjects
HIV (Viruses) -- Care and treatment, Antiviral agents -- Analysis, Highly active antiretroviral therapy -- Analysis, Long-term care of the sick -- Analysis, Consortia -- Analysis, Epidemiology -- Analysis, AIDS treatment -- Analysis, Consortium, Biological sciences, World Health Organization
Abstract

Background While national adoption of universal HIV treatment guidelines has led to improved, timely uptake of antiretroviral therapy (ART), longer-term care outcomes are understudied. There is little data from real-world service delivery settings on patient attrition, viral load (VL) monitoring, and viral suppression (VS) at 24 and 36 months after HIV treatment initiation. Methods and findings For this retrospective cohort analysis, we used observational data from 25 countries in the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium's Asia-Pacific, Central Africa, East Africa, Central/South America, and North America regions for patients who were ART naïve and aged [greater than or equal to]15 years at care enrollment between 24 months before and 12 months after national adoption of universal treatment guidelines, occurring 2012 to 2018. We estimated crude cumulative incidence of loss-to-clinic (CI-LTC) at 12, 24, and 36 months after enrollment among patients enrolling in care before and after guideline adoption using competing risks regression. Guideline change-associated hazard ratios of LTC at each time point after enrollment were estimated via cause-specific Cox proportional hazards regression models. Modified Poisson regression was used to estimate relative risks of retention, VL monitoring, and VS at 12, 24, and 36 months after ART initiation. There were 66,963 patients enrolling in HIV care at 109 clinics with [greater than or equal to]12 months of follow-up time after enrollment (46,484 [69.4%] enrolling before guideline adoption and 20,479 [30.6%] enrolling afterwards). More than half (54.9%) were females, and median age was 34 years (interquartile range [IQR]: 27 to 43). Mean follow-up time was 51 months (standard deviation: 17 months; range: 12, 110 months). Among patients enrolling before guideline adoption, crude CI-LTC was 23.8% (95% confidence interval [95% CI] 23.4, 24.2) at 12 months, 31.0% (95% CI [30.6, 31.5]) at 24 months, and 37.2% (95% [CI 36.8, 37.7]) at 36 months after enrollment. Adjusting for sex, age group, enrollment CD4, clinic location and type, and country income level, enrolling in care and initiating ART after guideline adoption was associated with increased hazard of LTC at 12 months (adjusted hazard ratio [aHR] 1.25 [95% CI 1.08, 1.44]; p = 0.003); 24 months (aHR 1.38 [95% CI 1.19, 1.59]; p < .001); and 36 months (aHR 1.34 [95% CI 1.18, 1.53], p < .001) compared with enrollment before guideline adoption, with no before-after differences among patients with no record of ART initiation by end of follow-up. Among patients retained after ART initiation, VL monitoring was low, with marginal improvements associated with guideline adoption only at 12 months after ART initiation. Among those with VL monitoring, VS was high at each time point among patients enrolling before guideline adoption (86.0% to 88.8%) and afterwards (86.2% to 90.3%), with no substantive difference associated with guideline adoption. Study limitations include lags in and potential underascertainment of care outcomes in real-world service delivery data and potential lack of generalizability beyond IeDEA sites and regions included in this analysis. Conclusions In this study, adoption of universal HIV treatment guidelines was associated with lower retention after ART initiation out to 36 months of follow-up, with little change in VL monitoring or VS among retained patients. Monitoring long-term HIV care outcomes remains critical to identify and address causes of attrition and gaps in HIV care quality., Author(s): Ellen Brazier 1,2,*, Olga Tymejczyk 1, Kara Wools-Kaloustian 3, Awachana Jiamsakul 4, Marco Tulio Luque Torres 5, Jennifer S. Lee 6, Lisa Abuogi 7, Vohith Khol 8, Fernando Mejía [...]

Published
2024
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9. Dolutegravir plus boosted darunavir versus recommended standard-of-care antiretroviral regimens in people with HIV-1 for whom recommended first-line non-nucleoside reverse transcriptase inhibitor therapy has failed (D2EFT): an open-label, randomised, phase 3b/4 trial

Author

Matthews, Gail, Jacoby, Simone, Borok, Margaret, Eriobu, Nnakelu, Kaplan, Richard, Kumarasamy, Nagalingeswaran, Bennet, Jaclyn Ann, Avihingsanon, Anchalee, Chetchotisakd, Ploenchan, Wagner Cardoso, Sandra, Azwa, Iskandar, Losso, Marcelo, Brown, Dannae, Arlinda, Dona, Hutchinson, Jolie, Kelleher, Anthony, Cisse, Mohamed, Dao, Sounkalo, Polizzotto, Mark, Emery, Sean, Law, Matthew, Papot, Emmanuelle, Karyana, Muhammad, Lupo, Sergio, Solari, Ana Melisa, Grinsztejn, Beatriz, Wolff, Marcello, Andrade-Villanueva, Jaime, Mosqueda Gómez, Juan Luis, Chow, Ting Soo, Mohapi, Lerato, Yunihastuti, Evy, Hadi, Usman, Katu, Sudirman, Subronto, Yanri Wijayanti, Lane, H. Clifford, and Perelis, Leonardo

Published
2024
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11. Associations between change in BMI and the risk of hypertension and dyslipidaemia in people receiving integrase strand-transfer inhibitors, tenofovir alafenamide, or both compared with other contemporary antiretroviral regimens: a multicentre, prospective observational study from the RESPOND consortium cohorts

Author

Byonanebye, Dathan M, Polizzotto, Mark N, Maltez, Fernando, Rauch, Andri, Grabmeier-Pfistershammer, Katharina, Wit, Ferdinand, De Wit, Stéphane, Castagna, Antonella, d'Arminio Monforte, Antonella, Mussini, Cristina, Wasmuth, Jan-Christian, Fontas, Eric, Abela, Irene, Sarcletti, Mario, Bansi-Matharu, Loveleen, Jaschinski, Nadine, Peters, Lars, Hosein, Sean R, Vannappagari, Vani, Cohen, Cal, Bissio, Emiliano, Mocroft, Amanda, Law, Matthew, Ryom, Lene, and Petoumenos, Kathy

Published
2024
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13. Long-term cost-effectiveness of a melanoma prevention program using genomic risk information compared with standard prevention advice in Australia

Author

Newson, Ainsley J., Morton, Rachael L., Kimlin, Michael, Keogh, Louise, Law, Matthew, Kirk, Judy, Dobbinson, Suzanne J., Kanetsky, Peter, Mann, Graham, Dawkins, Hugh, Savard, Jacqueline, Dunlop, Kate, Trevena, Lyndal, Jenkins, Mark, Allen, Martin, Butow, Phyllis, Wordsworth, Sarah, Lo, Serigne, Low, Cynthia, Smit, Amelia K., Espinoza, David, Cust, Anne E., Law, Chi Kin, Fernandez-Penas, Pablo, Nieweg, Omgo E., and Menzies, Alexander M.

Published
2023
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17. The association between genetically elevated polyunsaturated fatty acids and risk of cancer

Author

Tintle, Nathan, Rice, Terri, Cheng, Iona, Jenkins, Mark, Gallinger, Steve, Cornish, Alex J., Sud, Amit, Vijayakrishnan, Jayaram, Wrensch, Margaret, Johansson, Mattias, Norman, Aaron D., Klein, Alison, Clay-Gilmour, Alyssa, Franke, Andre, Ardisson Korat, Andres V., Wheeler, Bill, Nilsson, Björn, Smith, Caren, Heng, Chew-Kiat, Song, Ci, Riadi, David, Claus, Elizabeth B., Ellinghaus, Eva, Ostroumova, Evgenia, Hosnijeh, de Vathaire, Florent, Cugliari, Giovanni, Matullo, Giuseppe, Oi-Lin Ng, Irene, Passow, Jeanette E., Foo, Jia Nee, Han, Jiali, Liu, Jianjun, Barnholtz-Sloan, Jill, Schildkraut, Joellen M., Maris, John, Wiemels, Joseph L., Hemminki, Kari, Yang, Keming, Kiemeney, Lambertus A., Wu, Lang, Amundadottir, Laufey, Stern, Marc-Henri, Boutron, Marie-Christine, Iles, Mark Martin, Purdue, Mark P., Stanulla, Martin, Bondy, Melissa, Gaudet, Mia, Mobuchon, Lenha, Camp, Nicola J., Sham, Pak Chung, Guénel, Pascal, Brennan, Paul, Taylor, Philip R., Ostrom, Quinn, Stolzenberg-Solomon, Rachael, Dorajoo, Rajkumar, Houlston, Richard, Jenkins, Robert B., Diskin, Sharon, Berndt, Sonja I., Tsavachidis, Spiridon, Channock, Stephen J., Harrison, Tabitha, Galesloot, Tessel, Gyllensten, Ulf, Joseph, Vijai, Shi, Y., Yang, Wenjian, Lin, Yi, Van Den Eeden, Stephen K., Haycock, Philip C., Borges, Maria Carolina, Burrows, Kimberley, Lemaitre, Rozenn N., Burgess, Stephen, Khankari, Nikhil K., Tsilidis, Konstantinos K., Gaunt, Tom R., Hemani, Gibran, Zheng, Jie, Truong, Therese, Birmann, Brenda M., OMara, Tracy, Spurdle, Amanda B., Iles, Mark M., Law, Matthew H., Slager, Susan L., Saberi Hosnijeh, Fatemeh, Mariosa, Daniela, Cotterchio, Michelle, Cerhan, James R., Peters, Ulrike, Enroth, Stefan, Gharahkhani, Puya, Le Marchand, Loic, Williams, Ann C., Block, Robert C., Amos, Christopher I., Hung, Rayjean J., Zheng, Wei, Gunter, Marc J., Smith, George Davey, Relton, Caroline, and Martin, Richard M.

Published
2023
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18. Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers.

Author

Zhang, Yan Dora, Hurson, Amber N, Zhang, Haoyu, Choudhury, Parichoy Pal, Easton, Douglas F, Milne, Roger L, Simard, Jacques, Hall, Per, Michailidou, Kyriaki, Dennis, Joe, Schmidt, Marjanka K, Chang-Claude, Jenny, Gharahkhani, Puya, Whiteman, David, Campbell, Peter T, Hoffmeister, Michael, Jenkins, Mark, Peters, Ulrike, Hsu, Li, Gruber, Stephen B, Casey, Graham, Schmit, Stephanie L, O'Mara, Tracy A, Spurdle, Amanda B, Thompson, Deborah J, Tomlinson, Ian, De Vivo, Immaculata, Landi, Maria Teresa, Law, Matthew H, Iles, Mark M, Demenais, Florence, Kumar, Rajiv, MacGregor, Stuart, Bishop, D Timothy, Ward, Sarah V, Bondy, Melissa L, Houlston, Richard, Wiencke, John K, Melin, Beatrice, Barnholtz-Sloan, Jill, Kinnersley, Ben, Wrensch, Margaret R, Amos, Christopher I, Hung, Rayjean J, Brennan, Paul, McKay, James, Caporaso, Neil E, Berndt, Sonja I, Birmann, Brenda M, Camp, Nicola J, Kraft, Peter, Rothman, Nathaniel, Slager, Susan L, Berchuck, Andrew, Pharoah, Paul DP, Sellers, Thomas A, Gayther, Simon A, Pearce, Celeste L, Goode, Ellen L, Schildkraut, Joellen M, Moysich, Kirsten B, Amundadottir, Laufey T, Jacobs, Eric J, Klein, Alison P, Petersen, Gloria M, Risch, Harvey A, Stolzenberg-Solomon, Rachel Z, Wolpin, Brian M, Li, Donghui, Eeles, Rosalind A, Haiman, Christopher A, Kote-Jarai, Zsofia, Schumacher, Fredrick R, Al Olama, Ali Amin, Purdue, Mark P, Scelo, Ghislaine, Dalgaard, Marlene D, Greene, Mark H, Grotmol, Tom, Kanetsky, Peter A, McGlynn, Katherine A, Nathanson, Katherine L, Turnbull, Clare, Wiklund, Fredrik, Breast Cancer Association Consortium (BCAC), Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON), Colon Cancer Family Registry (CCFR), Transdisciplinary Studies of Genetic Variation in Colorectal Cancer (CORECT), Endometrial Cancer Association Consortium (ECAC), Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), Melanoma Genetics Consortium (GenoMEL), Glioma International Case-Control Study (GICC), International Lung Cancer Consortium (ILCCO), Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Consortium, International Consortium of Investigators Working on Non-Hodgkin’s Lymphoma Epidemiologic Studies (InterLymph), Ovarian Cancer Association Consortium (OCAC), Oral Cancer GWAS, Pancreatic Cancer Case-Control Consortium (PanC4), Pancreatic Cancer Cohort Consortium (PanScan), and Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL)

Subjects
Breast Cancer Association Consortium, Barrett’s and Esophageal Adenocarcinoma Consortium, Colon Cancer Family Registry, Transdisciplinary Studies of Genetic Variation in Colorectal Cancer, Endometrial Cancer Association Consortium, Genetics and Epidemiology of Colorectal Cancer Consortium, Melanoma Genetics Consortium, Glioma International Case-Control Study, International Lung Cancer Consortium, Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Consortium, International Consortium of Investigators Working on Non-Hodgkin’s Lymphoma Epidemiologic Studies, Ovarian Cancer Association Consortium, Oral Cancer GWAS, Pancreatic Cancer Case-Control Consortium, Pancreatic Cancer Cohort Consortium, Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome, Renal Cancer GWAS, Testicular Cancer Consortium, Animals, Humans, Neoplasms, Genetic Predisposition to Disease, Incidence, Risk Assessment, Risk Factors, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Models, Genetic, Female, Male, Genome-Wide Association Study, Human Genome, Prevention, Cancer, Prostate Cancer, Genetics, Urologic Diseases, 2.1 Biological and endogenous factors
Abstract

Genome-wide association studies (GWAS) have led to the identification of hundreds of susceptibility loci across cancers, but the impact of further studies remains uncertain. Here we analyse summary-level data from GWAS of European ancestry across fourteen cancer sites to estimate the number of common susceptibility variants (polygenicity) and underlying effect-size distribution. All cancers show a high degree of polygenicity, involving at a minimum of thousands of loci. We project that sample sizes required to explain 80% of GWAS heritability vary from 60,000 cases for testicular to over 1,000,000 cases for lung cancer. The maximum relative risk achievable for subjects at the 99th risk percentile of underlying polygenic risk scores (PRS), compared to average risk, ranges from 12 for testicular to 2.5 for ovarian cancer. We show that PRS have potential for risk stratification for cancers of breast, colon and prostate, but less so for others because of modest heritability and lower incidence.

Published
2020

19. Overlapping genetic architecture between Parkinson disease and melanoma

Author

Dube, Umber, Ibanez, Laura, Budde, John P, Benitez, Bruno A, Davis, Albert A, Harari, Oscar, Iles, Mark M, Law, Matthew H, Brown, Kevin M, and Cruchaga, Carlos

Subjects
Biomedical and Clinical Sciences, Neurosciences, Neurodegenerative, Aging, Biotechnology, Prevention, Cancer, Human Genome, Parkinson's Disease, Brain Disorders, Clinical Research, Genetics, 2.1 Biological and endogenous factors, Aetiology, Neurological, Case-Control Studies, Genome-Wide Association Study, Humans, Melanoma, Multifactorial Inheritance, Parkinson Disease, Skin Neoplasms, 23andMe Research Team, Melanoma-Meta-analysis Consortium, Genetic correlation, Parkinson disease, Polygenic, Shared genetic architecture, TWAS, Clinical Sciences, Neurology & Neurosurgery
Abstract

Epidemiologic studies have reported inconsistent results regarding an association between Parkinson disease (PD) and cutaneous melanoma (melanoma). Identifying shared genetic architecture between these diseases can support epidemiologic findings and identify common risk genes and biological pathways. Here, we apply polygenic, linkage disequilibrium-informed methods to the largest available case-control, genome-wide association study summary statistic data for melanoma and PD. We identify positive and significant genetic correlation (correlation: 0.17, 95% CI 0.10-0.24; P = 4.09 × 10-06) between melanoma and PD. We further demonstrate melanoma and PD-inferred gene expression to overlap across tissues (correlation: 0.14, 95% CI 0.06 to 0.22; P = 7.87 × 10-04) and highlight seven genes including PIEZO1, TRAPPC2L, and SOX6 as potential mediators of the genetic correlation between melanoma and PD. These findings demonstrate specific, shared genetic architecture between PD and melanoma that manifests at the level of gene expression.

Published
2020

20. Global Biobank analyses provide lessons for developing polygenic risk scores across diverse cohorts

Author

Zhou, Wei, Kanai, Masahiro, Wu, Kuan-Han H., Rasheed, Humaira, Tsuo, Kristin, Hirbo, Jibril B., Wang, Ying, Bhattacharya, Arjun, Zhao, Huiling, Namba, Shinichi, Surakka, Ida, Wolford, Brooke N., Lo Faro, Valeria, Lopera-Maya, Esteban A., Läll, Kristi, Favé, Marie-Julie, Chapman, Sinéad B., Karjalainen, Juha, Kurki, Mitja, Mutaamba, Maasha, Partanen, Juulia J., Brumpton, Ben M., Chavan, Sameer, Chen, Tzu-Ting, Daya, Michelle, Ding, Yi, Feng, Yen-Chen A., Gignoux, Christopher R., Graham, Sarah E., Hornsby, Whitney E., Ingold, Nathan, Johnson, Ruth, Laisk, Triin, Lin, Kuang, Lv, Jun, Millwood, Iona Y., Palta, Priit, Pandit, Anita, Preuss, Michael H., Thorsteinsdottir, Unnur, Uzunovic, Jasmina, Zawistowski, Matthew, Zhong, Xue, Campbell, Archie, Crooks, Kristy, de Bock, Geertruida H., Douville, Nicholas J., Finer, Sarah, Fritsche, Lars G., Griffiths, Christopher J., Guo, Yu, Hunt, Karen A., Konuma, Takahiro, Marioni, Riccardo E., Nomdo, Jansonius, Patil, Snehal, Rafaels, Nicholas, Richmond, Anne, Shortt, Jonathan A., Straub, Peter, Tao, Ran, Vanderwerff, Brett, Barnes, Kathleen C., Boezen, Marike, Chen, Zhengming, Chen, Chia-Yen, Cho, Judy, Smith, George Davey, Finucane, Hilary K., Franke, Lude, Gamazon, Eric R., Ganna, Andrea, Gaunt, Tom R., Ge, Tian, Huang, Hailiang, Huffman, Jennifer, Koskela, Jukka T., Lajonchere, Clara, Law, Matthew H., Li, Liming, Lindgren, Cecilia M., Loos, Ruth J.F., MacGregor, Stuart, Matsuda, Koichi, Olsen, Catherine M., Porteous, David J., Shavit, Jordan A., Snieder, Harold, Trembath, Richard C., Vonk, Judith M., Whiteman, David, Wicks, Stephen J., Wijmenga, Cisca, Wright, John, Zheng, Jie, Zhou, Xiang, Awadalla, Philip, Boehnke, Michael, Cox, Nancy J., Geschwind, Daniel H., Hayward, Caroline, Hveem, Kristian, Kenny, Eimear E., Lin, Yen-Feng, Mägi, Reedik, Martin, Hilary C., Medland, Sarah E., Okada, Yukinori, Palotie, Aarno V., Pasaniuc, Bogdan, Sanna, Serena, Smoller, Jordan W., Stefansson, Kari, van Heel, David A., Walters, Robin G., Zöllner, Sebastian, Martin, Alicia R., Willer, Cristen J., Daly, Mark J., Neale, Benjamin M., Lopera, Esteban, Kerminen, Sini, Wu, Kuan-Han, Bhatta, Laxmi, Brumpton, Ben, Deelen, Patrick, Murakami, Yoshinori, Willer, Cristen, and Hirbo, Jibril

Published
2023
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22. Meta-analysis fine-mapping is often miscalibrated at single-variant resolution

Author

Zhou, Wei, Kanai, Masahiro, Wu, Kuan-Han H., Rasheed, Humaira, Tsuo, Kristin, Hirbo, Jibril B., Wang, Ying, Bhattacharya, Arjun, Zhao, Huiling, Namba, Shinichi, Surakka, Ida, Wolford, Brooke N., Lo Faro, Valeria, Lopera-Maya, Esteban A., Läll, Kristi, Favé, Marie-Julie, Partanen, Juulia J., Chapman, Sinéad B., Karjalainen, Juha, Kurki, Mitja, Maasha, Mutaamba, Brumpton, Ben M., Chavan, Sameer, Chen, Tzu-Ting, Daya, Michelle, Ding, Yi, Feng, Yen-Chen A., Guare, Lindsay A., Gignoux, Christopher R., Graham, Sarah E., Hornsby, Whitney E., Ingold, Nathan, Ismail, Said I., Johnson, Ruth, Laisk, Triin, Lin, Kuang, Lv, Jun, Millwood, Iona Y., Moreno-Grau, Sonia, Nam, Kisung, Palta, Priit, Pandit, Anita, Preuss, Michael H., Saad, Chadi, Setia-Verma, Shefali, Thorsteinsdottir, Unnur, Uzunovic, Jasmina, Verma, Anurag, Zawistowski, Matthew, Zhong, Xue, Afifi, Nahla, Al-Dabhani, Kawthar M., Al Thani, Asma, Bradford, Yuki, Campbell, Archie, Crooks, Kristy, de Bock, Geertruida H., Damrauer, Scott M., Douville, Nicholas J., Finer, Sarah, Fritsche, Lars G., Fthenou, Eleni, Gonzalez-Arroyo, Gilberto, Griffiths, Christopher J., Guo, Yu, Hunt, Karen A., Ioannidis, Alexander, Jansonius, Nomdo M., Konuma, Takahiro, Michael Lee, Ming Ta, Lopez-Pineda, Arturo, Matsuda, Yuta, Marioni, Riccardo E., Moatamed, Babak, Nava-Aguilar, Marco A., Numakura, Kensuke, Patil, Snehal, Rafaels, Nicholas, Richmond, Anne, Rojas-Muñoz, Agustin, Shortt, Jonathan A., Straub, Peter, Tao, Ran, Vanderwerff, Brett, Vernekar, Manvi, Veturi, Yogasudha, Barnes, Kathleen C., Boezen, Marike, Chen, Zhengming, Chen, Chia-Yen, Cho, Judy, Smith, George Davey, Finucane, Hilary K., Franke, Lude, Gamazon, Eric R., Ganna, Andrea, Gaunt, Tom R., Ge, Tian, Huang, Hailiang, Huffman, Jennifer, Katsanis, Nicholas, Koskela, Jukka T., Lajonchere, Clara, Law, Matthew H., Li, Liming, Lindgren, Cecilia M., Loos, Ruth J.F., MacGregor, Stuart, Matsuda, Koichi, Olsen, Catherine M., Porteous, David J., Shavit, Jordan A., Snieder, Harold, Takano, Tomohiro, Trembath, Richard C., Vonk, Judith M., Whiteman, David C., Wicks, Stephen J., Wijmenga, Cisca, Wright, John, Zheng, Jie, Zhou, Xiang, Awadalla, Philip, Boehnke, Michael, Bustamante, Carlos D., Cox, Nancy J., Fatumo, Segun, Geschwind, Daniel H., Hayward, Caroline, Hveem, Kristian, Kenny, Eimear E., Lee, Seunggeun, Lin, Yen-Feng, Mbarek, Hamdi, Mägi, Reedik, Martin, Hilary C., Medland, Sarah E., Okada, Yukinori, Palotie, Aarno V., Pasaniuc, Bogdan, Rader, Daniel J., Ritchie, Marylyn D., Sanna, Serena, Smoller, Jordan W., Stefansson, Kari, van Heel, David A., Walters, Robin G., Zöllner, Sebastian, Biobank of the Americas, Biobank Japan Project, BioMe, BioVU, CanPath - Ontario Health Study, China Kadoorie Biobank Collaborative Group, Colorado Center for Personalized Medicine, deCODE Genetics, Estonian Biobank, FinnGen, Generation Scotland, Genes & Health Research Team, LifeLines, Mass General Brigham Biobank, Michigan Genomics Initiative, National Biobank of Korea, Penn Medicine BioBank, Qatar Biobank, The Qskin Sun and Health Study, Taiwan Biobank, The Hunt Study, Ucla Atlas Community Health Initiative, Uganda Genome Resource, Uk Biobank, Martin, Alicia R., Willer, Cristen J., Daly, Mark J., Neale, Benjamin M., and Elzur, Roy

Published
2022
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23. Multicentre double-blind randomised placebo-controlled trial evaluating the efficacy of the meningococcal B vaccine, 4CMenB (Bexsero), againstNeisseria gonorrhoeaeinfection in men who have sex with men: the GoGoVax study protocol

Author

Seib, Kate L, primary, Donovan, Basil, additional, Thng, Caroline, additional, Lewis, David A, additional, McNulty, Anna, additional, Fairley, Christopher K, additional, Yeung, Barbara, additional, Jin, Fengyi, additional, Fraser, Doug, additional, Bavinton, Benjamin R, additional, Law, Matthew, additional, Chen, Marcus Y, additional, Chow, Eric P F, additional, Whiley, David M, additional, Mackie, Brent, additional, Jennings, Michael P, additional, Jennison, Amy V, additional, Lahra, Monica M, additional, and Grulich, Andrew E, additional

Published
2024
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24. Motivational Interviewing as an Intervention to Improve Antiretroviral Treatment Initiation Among People who Inject Drugs (PWID): A Pilot Study in Jakarta and Bandung, Indonesia

Author

Sukmaningrum, Evi, primary, Ayu, Astri Parawita, additional, Wongso, Lydia Verina, additional, Handayani, Miasari, additional, Hendrianti, Sarahsita, additional, Kawi, Nurhayati Hamim, additional, Kusmayanti, Nur Aini, additional, Sulaiman, Nurjannah, additional, Irwanto, Irwanto, additional, Law, Matthew, additional, and Wisaksana, Rudi, additional

Published
2024
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25. Corrigendum to “Trends in decompensated cirrhosis and hepatocellular carcinoma among people with a hepatitis B notification in New South Wales” [JHEP Reports 4 (2022)]

Author

Bin Usman Shah, Syed Hassan, primary, Alavi, Maryam, additional, Hajarizadeh, Behzad, additional, Matthews, Gail V., additional, Martinello, Marianne, additional, Danta, Mark, additional, Amin, Janaki, additional, Law, Matthew G., additional, George, Jacob, additional, Valerio, Heather, additional, and Dore, Gregory J., additional

Published
2024
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26. Higher polygenic risk for melanoma is associated with improved survival in a high ultraviolet radiation setting

Author

Seviiri, Mathias, Scolyer, Richard A., Bishop, D. Timothy, Newton-Bishop, Julia A., Iles, Mark M., Lo, Serigne N., Stretch, Johnathan R., Saw, Robyn P. M., Nieweg, Omgo E., Shannon, Kerwin F., Spillane, Andrew J., Gordon, Scott D., Olsen, Catherine M., Whiteman, David C., Landi, Maria Teresa, Thompson, John F., Long, Georgina V., MacGregor, Stuart, and Law, Matthew H.

Published
2022
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28. Global Biobank Meta-analysis Initiative: Powering genetic discovery across human disease

Author

Zhou, Wei, Kanai, Masahiro, Wu, Kuan-Han H., Rasheed, Humaira, Tsuo, Kristin, Hirbo, Jibril B., Wang, Ying, Bhattacharya, Arjun, Zhao, Huiling, Namba, Shinichi, Surakka, Ida, Wolford, Brooke N., Lo Faro, Valeria, Lopera-Maya, Esteban A., Läll, Kristi, Favé, Marie-Julie, Partanen, Juulia J., Chapman, Sinéad B., Karjalainen, Juha, Kurki, Mitja, Maasha, Mutaamba, Brumpton, Ben M., Chavan, Sameer, Chen, Tzu-Ting, Daya, Michelle, Ding, Yi, Feng, Yen-Chen A., Guare, Lindsay A., Gignoux, Christopher R., Graham, Sarah E., Hornsby, Whitney E., Ingold, Nathan, Ismail, Said I., Johnson, Ruth, Laisk, Triin, Lin, Kuang, Lv, Jun, Millwood, Iona Y., Moreno-Grau, Sonia, Nam, Kisung, Palta, Priit, Pandit, Anita, Preuss, Michael H., Saad, Chadi, Setia-Verma, Shefali, Thorsteinsdottir, Unnur, Uzunovic, Jasmina, Verma, Anurag, Zawistowski, Matthew, Zhong, Xue, Afifi, Nahla, Al-Dabhani, Kawthar M., Al Thani, Asma, Bradford, Yuki, Campbell, Archie, Crooks, Kristy, de Bock, Geertruida H., Damrauer, Scott M., Douville, Nicholas J., Finer, Sarah, Fritsche, Lars G., Fthenou, Eleni, Gonzalez-Arroyo, Gilberto, Griffiths, Christopher J., Guo, Yu, Hunt, Karen A., Ioannidis, Alexander, Jansonius, Nomdo M., Konuma, Takahiro, Lee, Ming Ta Michael, Lopez-Pineda, Arturo, Matsuda, Yuta, Marioni, Riccardo E., Moatamed, Babak, Nava-Aguilar, Marco A., Numakura, Kensuke, Patil, Snehal, Rafaels, Nicholas, Richmond, Anne, Rojas-Muñoz, Agustin, Shortt, Jonathan A., Straub, Peter, Tao, Ran, Vanderwerff, Brett, Vernekar, Manvi, Veturi, Yogasudha, Barnes, Kathleen C., Boezen, Marike, Chen, Zhengming, Chen, Chia-Yen, Cho, Judy, Smith, George Davey, Finucane, Hilary K., Franke, Lude, Gamazon, Eric R., Ganna, Andrea, Gaunt, Tom R., Ge, Tian, Huang, Hailiang, Huffman, Jennifer, Katsanis, Nicholas, Koskela, Jukka T., Lajonchere, Clara, Law, Matthew H., Li, Liming, Lindgren, Cecilia M., Loos, Ruth J.F., MacGregor, Stuart, Matsuda, Koichi, Olsen, Catherine M., Porteous, David J., Shavit, Jordan A., Snieder, Harold, Takano, Tomohiro, Trembath, Richard C., Vonk, Judith M., Whiteman, David C., Wicks, Stephen J., Wijmenga, Cisca, Wright, John, Zheng, Jie, Zhou, Xiang, Awadalla, Philip, Boehnke, Michael, Bustamante, Carlos D., Cox, Nancy J., Fatumo, Segun, Geschwind, Daniel H., Hayward, Caroline, Hveem, Kristian, Kenny, Eimear E., Lee, Seunggeun, Lin, Yen-Feng, Mbarek, Hamdi, Mägi, Reedik, Martin, Hilary C., Medland, Sarah E., Okada, Yukinori, Palotie, Aarno V., Pasaniuc, Bogdan, Rader, Daniel J., Ritchie, Marylyn D., Sanna, Serena, Smoller, Jordan W., Stefansson, Kari, van Heel, David A., Walters, Robin G., Zöllner, Sebastian, Martin, Alicia R., Willer, Cristen J., Daly, Mark J., and Neale, Benjamin M.

Published
2022
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31. Multi-Trait Genetic Analysis Identifies Autoimmune Loci Associated with Cutaneous Melanoma

Author

Agee, Michelle, Aslibekyan, Stella, Auton, Adam, Babalola, Elizabeth, Bell, Robert K., Bielenberg, Jessica, Bryc, Katarzyna, Bullis, Emily, Cameron, Briana, Coker, Daniella, Cuellar Partida, Gabriel, Dhamija, Devika, Das, Sayantan, Elson, Sarah L., Filshtein, Teresa, Fletez-Brant, Kipper, Fontanillas, Pierre, Freyman, Will, Gandhi, Pooja M., Heilbron, Karl, Hicks, Barry, Hinds, David A., Huber, Karen E., Jewett, Ethan M., Kleinman, Aaron, Kukar, Katelyn, Lin, Keng-Han, Lowe, Maya, Luff, Marie K., McCreight, Jennifer C., McIntyre, Matthew H., McManus, Kimberly F., Micheletti, Steven J., Moreno, Meghan E., Mountain, Joanna L., Mozaffari, Sahar V., Nandakumar, Priyanka, Noblin, Elizabeth S., O'Connell, Jared, Petrakovitz, Aaron A., Poznik, G. David, Shastri, Anjali J., Shelton, Janie F., Shi, Jingchunzi, Shringarpure, Suyash, Tran, Vinh, Tung, Joyce Y., Wang, Xin, Wang, Wei, Weldon, Catherine H., Wilton, Peter, Liyanage, Upekha E., MacGregor, Stuart, Bishop, D. Timothy, Shi, Jianxin, An, Jiyuan, Ong, Jue Sheng, Han, Xikun, Scolyer, Richard A., Martin, Nicholas G., Medland, Sarah E., Byrne, Enda M., Green, Adèle C., Saw, Robyn P.M., Thompson, John F., Stretch, Jonathan, Spillane, Andrew, Jiang, Yunxuan, Tian, Chao, Gordon, Scott G., Duffy, David L., Olsen, Catherine M., Whiteman, David C., Long, Georgina V., Iles, Mark M., Landi, Maria Teresa, and Law, Matthew H.

Published
2022
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34. Impact of personal genomic risk information on melanoma prevention behaviors and psychological outcomes: a randomized controlled trial

Author

Smit, Amelia K., Allen, Martin, Beswick, Brooke, Butow, Phyllis, Dawkins, Hugh, Dobbinson, Suzanne J., Dunlop, Kate L., Espinoza, David, Fenton, Georgina, Kanetsky, Peter A., Keogh, Louise, Kimlin, Michael G., Kirk, Judy, Law, Matthew H., Lo, Serigne, Low, Cynthia, Mann, Graham J., Reyes-Marcelino, Gillian, Morton, Rachael L., Newson, Ainsley J., Savard, Jacqueline, Trevena, Lyndal, Wordsworth, Sarah, and Cust, Anne E.

Published
2021
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35. Archaeology in the Western Isles : the molluscan evidence

Author

Law, Matthew

Subjects
936.11, CC Archaeology
Abstract

Using assemblages of marine and non-marine mollusc shells from recent excavations in the Western Isles of Scotland, with reference to previously published studies, this thesis contributes to an enhanced understanding of the cultural palaeoecology of insular societies. Chaoter 1 sets out the topics that will be covered in this thesis. Chapter 2 introduces the methods and principles that drive molluscan analysis; Chapter 3 outlines the natural history of the Western Isles; and Chapter 4 the archaeology. Previous work on molluscs from the islands are summarised in Chapter 5, and emergent themes identified. Chapter 6 presents the results of analyses of new non-marine molluscan assemblages from 9 sites, ranging in date from the Mesolithic to the Norse period. Comparative data collected from a transect of samples for modern snails are also presented, along with a statistical meta-analysis of the data. Chapter 7 presents the results of marine shell analyses from 4 sites, ranging in date from the Early Bronze Age to the Norse period. The results are discussed in terms of their regional and wider significance in Chapter 8, and the thesis concluded in Chapter 9. Studying non-marine and marine molluscs from a wide range of sites across the islands has made important contributions to the archaeology of the Western Isles. The movement of new species of snail into and across the islands emphasises the connectedness of prehistoric communities across wider social networks on the Atlantic coast of Europe. The study of non-marine molluscs and the use of statistical analysis contributes to a broader understanding of taphonomy and site formation processes. Combined analysis of marine and non-marine mollusc shells highlights the agricultural practices and land use of prehistoric and Norse farmers. Studies of larger marine shells indicate changing tastes at the time of increasing contact with the Norse diaspora.

Published
2018

36. Factors associated with hepatitis C treatment uptake among females of childbearing age in New South Wales, Australia: A population‐based study.

Author

Valerio, Heather, Alavi, Maryam, Marshall, Alison D., Hajarizadeh, Behzad, Amin, Janaki, Law, Matthew, Tillakeratne, Shane, George, Jacob, Degenhardt, Louisa, Grebely, Jason, Matthews, Gail V., and Dore, Gregory J.

Subjects
CHILDBEARING age, HEPATITIS C, INDIGENOUS Australians, DRUG addiction, HEPATITIS C virus
Abstract

Introduction: Females of childbearing age with hepatitis C virus (HCV) face increased marginalisation with intersecting, sex‐specific barriers to direct acting antiviral (DAA) therapy. We assessed the factors associated with uptake of DAA therapy among females of childbearing age, including those with evidence of recent drug dependence. Methods: HCV notifications in New South Wales, Australia (1995–2017) were linked to opioid agonist therapy (OAT), hospitalisations, incarcerations, perinatal, HIV notifications, deaths and prescription databases. Recent drug dependence was defined as hospitalisation due to injectable drugs or receipt of OAT occurring in the DAA era (2016–2018). Logistic regression was used to analyse factors associated with DAA uptake among females of childbearing age (18–44), including those with recent drug dependence. Results: Among 57,467 people with evidence of chronic HCV in the DAA era (2016–2018), 20,161 (35%) were female, including 33% (n = 6563/20,161) of childbearing age (18–44). Among all females of childbearing age (n = 6563) and those with evidence of recent drug dependence (n = 2278/6563, 35%), DAA uptake was lower among those who had given birth in the DAA era (vs. no birth record, all females of childbearing age; aOR: 0.74, 95% CI 0.61, 0.89; those with recent drug dependence; aOR 0.69, 95% CI 0.51, 0.93) and Aboriginal and Torres Strait Islander peoples (all females of childbearing age; aOR 0.81, 95% CI 0.71, 0.93; those with recent drug dependence aOR 0.75, 95% CI 0.62, 0.90). Conclusion: Females of childbearing age should be considered a key population for DAA therapy. Enhancing antenatal and postnatal HCV care may be critical in the pursuit towards elimination. [ABSTRACT FROM AUTHOR]

Published
2024
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37. Global estimates of viral suppression in children and adolescents and adults on antiretroviral therapy adjusted for missing viral load measurements: a multiregional, retrospective cohort study in 31 countries

Author

Han, Win Min, Law, Matthew G, Egger, Matthias, Wools-Kaloustian, Kara, Moore, Richard, McGowan, Catherine, Kumarasamy, Nagalingesawaran, Desmonde, Sophie, Edmonds, Andrew, Davies, Mary-Ann, Yiannoutsos, Constantin, Althoff, Keri N, Cortes, Claudia P, Mohamed, Thahira Jamal, Jaquet, Antoine, Anastos, Kathryn, Euvrard, Jonathan, Castelnuovo, Barbara, Salters, Kate, Coelho, Lara Esteves, Ekouevi, Didier K, Eley, Brian, Diero, Lameck, Zaniewski, Elizabeth, Ford, Nathan, Sohn, Annette H, and Kariminia, Azar

Published
2021
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39. Contemporary antiretrovirals and body-mass index: a prospective study of the RESPOND cohort consortium

Author

Bansi-Matharu, Loveleen, Phillips, Andrew, Oprea, Cristiana, Grabmeier-Pfistershammer, Katharina, Günthard, Huldrych F, De Wit, Stephane, Guaraldi, Giovanni, Vehreschild, Jorg J, Wit, Ferdinand, Law, Matthew, Wasmuth, Jan-Christian, Chkhartishvili, Nikoloz, d'Arminio Monforte, Antonella, Fontas, Eric, Vesterbacka, Jan, Miro, Jose M, Castagna, Antonella, Stephan, Christoph, Llibre, Josep M, Neesgaard, Bastian, Greenberg, Lauren, Smith, Colette, Kirk, Ole, Duvivier, Claudine, Dragovic, Gordana, Lundgren, Jens, Dedes, Nikos, Knudsen, Andreas, Gallant, Joel, Vannappagari, Vani, Peters, Lars, Elbirt, Daniel, Sarcletti, Mario, Braun, Dominique L, Necsoi, Coca, Mussini, Cristina, Muccini, Camilla, Bolokadze, Natalie, Hoy, Jennifer, Mocroft, Amanda, and Ryom, Lene

Published
2021
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41. Affinity Diagramming with a Robot

Author

Law, Matthew V., primary, Nwagwu, Nnamdi, additional, Kwatra, Amritansh, additional, Lee, Seo-young, additional, DiAngelis, Daniel M., additional, Yu, Naifang, additional, Gonzalez-Pumariega, Gonzalo, additional, Rajesh, Amit, additional, and Hoffman, Guy, additional

Published
2024
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42. Delabeling, safety, and impact of β-lactam allergy testing: A systematic review

Author

Loprete, Jacqueline, primary, Richardson, Robyn, additional, Bramah, Valerie, additional, Comben, Simon, additional, Li, Timothy, additional, Beiglari, Liam, additional, O’Neill, Robert, additional, McEwan, Callum, additional, Carr, Andrew, additional, Tong, Winnie, additional, Campbell, Dianne, additional, Wong, Melanie, additional, Evans, Louise, additional, Post, Jeffrey, additional, Torda, Adrienne, additional, Kane, Alisa, additional, Kelleher, Anthony, additional, Wainstein, Brynn, additional, McMullan, Brendan, additional, and Law, Matthew, additional

Published
2023
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43. Antiseptic mouthwash for gonorrhoea prevention (OMEGA): a randomised, double-blind, parallel-group, multicentre trial

Author

Chow, Eric P F, Williamson, Deborah A, Hocking, Jane S, Law, Matthew G, Maddaford, Kate, Bradshaw, Catriona S, McNulty, Anna, Templeton, David J, Moore, Richard, Murray, Gerald L, Danielewski, Jennifer A, Wigan, Rebecca, Chen, Marcus Y, Guy, Rebecca J, Zhang, Lei, Donovan, Basil, Grulich, Andrew E, Kaldor, John M, Whiley, David M, Cornelisse, Vincent J, Howden, Benjamin P, Lewis, David A, Read, Tim R H, and Fairley, Christopher K

Published
2021
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44. Service delivery challenges in HIV care during the first year of the COVID‐19 pandemic: results from a site assessment survey across the global IeDEA consortium

Author

Brazier, Ellen, Ajeh, Rogers, Maruri, Fernanda, Musick, Beverly, Freeman, Aimee, Wester, C. William, Lee, Man?Po, Shamu, Tinei, Ramírez, Brenda Crabtree, D' Almeida, Marcelline, Wools?Kaloustian, Kara, Kumarasamy, N., Althoff, Keri N., Twizere, Christella, Grinsztejn, Beatriz, Tanser, Frank, Messou, Eugène, Byakwaga, Helen, Duda, Stephany N., Nash, Denis, Chansilpa, Chidchon, Dougherty, Trevor, Karminia, Azar, Law, Matthew, Ross, Jeremy, Sohn, Annette, Aguirre, Ivette, Baker, David, Bloch, Mark, Cabot, Safaa, Carr, Andrew, Couldwell, Deborah, Edwards, Sian, Eu, Beng, Farlow, Heather, Finlayson, Robert, Gunathilake, Manoji, Hazlewood, Cherie, Hoy, Jennifer, Langton?Lockton, Julian, Le, Jacqueline, Leprince, Elizabeth, Minc, Ariane, Moore, Richard, O'Sullivan, Maree, Roth, Norm, Rowling, Dianne, Russell, Darren, Ryder, Nathan, Saunders, Craig, Silvers, Julie, Smith, David J., Sowden, David, Sweeney, Grant, Tan, Lynn, Teague, Ricard, Templeton, David, Thng, Caroline, Woolley, Ian, Khol, Vohith, Ly, Penh Sun, Li, Tsz Hei, Po, Lee Man, Kinikar, Aarti, Kumarasamy, Nagalingeswaran, Mundhe, Sanjay, Pujari, Sanjay, Sangle, Shashikala, Nimkar, Smita, Jassin, Madelein, Kurniati, Nia, Merati, Tuti Parwati, Muktiarti, Dina, Amalia, Rizqi, Sukmawati, Ni Made Dewi Dian, Wati, Ketut Dewi Kumara, Yunihastuti, Evy, Tanuma, Junko, Choi, Jun Yong, Azwa, Raja Iskandar Shah Raja, Cheng, Chan Kwai, Gani, Yasmin Mohamed, Mohamed, Thahira Jamal, Moy, Fong Siew, Nallusamy, Revathy, Nor, Mohamad Zulfahami Mohd, Rudi, Nuraini, Shyan, Wong Peng, Yusoff, Nik Khairulddin Nik, Ditangco, Rossana, Chan, Yu?Jiun, Wu, Pei?Chieh, Wu, Ping?Feng, Avihingsanon, Anchalee, Chaiwarith, Romanee, Chokephaibulkit, Kulkanya, Khusuwan, Suwimon, Kiertiburanakul, Sasisopin, Kosalaraksa, Pope, Lumbiganon, Pagakrong, Ounchanam, Pradtana, Puthanakit, Thanyawee, Rungmaitree, Supattra, Solai, Nuttarika, Sudjaritruk, Tavitiya, An, Vu Thien, Cuong, Do Duy, Do, Chau Viet, Huy, Bui Vu, Quy, Tuan, Van Nguyen, Kinh, Nguyen, Luan, Nguyen, Van Lam, Nguyen, Yen Thi, Nong, Vuong Minh, Truong, Huu Khanh, Tuyen, Ngo Thi Thu, Mcgowan, Catherine C., Duda, Stephany, Cahn, Florencia, Cahn, Pedro, Cesar, Carina, Fink, Valeria, Sued, Omar, Coelho, Lara, Machado, Daisy Maria, Pinto, Jorge, Wolff, Marcelo, Rouzier, Vanessa, Padgett, Denis, Gotuzzo, Eduardo, Biziragusenyuka, Jérémie, Gateretse, Patrick, Nimbona, Pelagie, Niyonkuru, Olive, Twizere, Christelle, Anicetus, Surreng, Djenabou, Amadou, Enow, Priscilla, Mbu, Eyongetah, Manga, Martin, Ndobe, Mercy, Nasah, Judith, Ekossono, Elle Nathalie Syntyche, Bouseko, Mireille Teno, Kitetele, Faustin, Lelo, Patricia, Diafouka, Merlin Isidore Justin, Mafoua, Adolphe, Nsonde, Dominique Mahambou, Bihira, Uitonze Aime Maurice, Dusabe, Marie Chantal, Feza, Rosine, Habanabashaka, Jean Claude, Habumuremyi, Viateur, Igizeneza, Ernestine, Kamigisha, Anne Marie, Kubwimana, Gallican, Maniriho, Gilbert, Mbaraga, Gilbert, Muhoza, Benjamin, Mukakarangwa, Jeanne, Mukamana, Joyce, Mukanyirigira, Patricie, Mukeshimana, Yvone Claude, Munyaneza, Athanase, Murenzi, Gad, Musaninyange, Jacqueline, Nyiraneza, Jules Ndumuhire, Ntarambirwa, Fidele, Nyiraneza, Marie Louise, Tuyishime, Josette, Tuyishimire, Yvonne, Ubandutira, Alexis, Umugiraneza, Florance, Umugwaneza, Rosine, Uwamahoro, Olive, Uwamahoro, Pauline, Uwambaje, Marie Victoire, Uwimpuhwe, Clarisse, Uwiragiye, Siphora, Kuhn, Yee Yee, Adera, Felix, Adhiambo, Beatricec, Aggrey, Khaemba, Akadikor, Daniel, Ambulla, Felix, Apiyo, Dorah, Ariya, Patrick, Atemba, Naftal, Ayodi, Fridah, Benard, Chirchir, Bett, Maureen, Birgen, Serafine, Bwalei, Rael, Chebon, Nancy, Chebor, Valentine Jirry, Chebuiywo, Philip, Chemutai, Jacline, Chepkorir, Emily, Chepseba, Carolyne, Chirchir, John, Diero, Lameck, Dukwa, Benard, Elphas, Alice, Etyang, Tom, Idiama, Agnes, Jebichuko, Ann, Jepchumba, Delvine, Juma, Churchill, Juma, Maureen, Juma, Sheila, Kadima, Julie, Karani, Rose, Keitany, Christopher, Keter, Pricilla, Kiavoga, Lucy, Kibet, Harrison, Kimutai, Ruth, Kiplagat, Mutai, Kiprono, Wilfred, Kipruto, Nicholas Kogei, Kirimi, Asenath, Koech, Zeddy, Kosgei, Carolyne, Kutto, Karen, Kweyu, Mildred, Liech, Ephraim Kenneth, Limo, Milka, Maina, Rose, Marumbu, Priscah, Masese, Agnes, Mochotto, Patricia, Molly, Omudeck, Momanyi, Tom, Murutu, John W., Mwanda, Praxidis, Ndakalu, Lillian, Nderitu, Rose N., Obatsa, Sarah, Obiga, Fredrick, Oboya, Moses, Odhiambo, Joseph, Olaya, George, Omanyala, Oscar, Oray, Christine, Otieno, Molly, Otwane, Modesta Toto, Ouma, Paul, Owuor, Charles, Pepela, Doris Tutu, Pessah, Collins, Rotich, Evans, Rotich, Edwin K., Rutto, Titus C., Shikuku, Monica, Sibweche, Rose Naliaka, Simiyu, Robert Wanyonyi, Siria, Hellen, Some, Michael, Songok, Winnie Cherotich, Tanui, Immaculate, Wafula, Grace, Wambura, Rebecca, Wanjala, Ellah, Wanyama, Carolyne, Wanyonyi, Hellen, Woyakapel, Emmanuel, Zelbabel, Wandera, Gwimo, Dikengela, Kinyota, Ester, Lwali, Jerome, Lyamuya, Rita, Machemba, Richard, Mathias, Julia, Mkombachepa, Lilian, Mokiwa, Athuman, Mushi, Ombeni, Ndunguru, Charles, Ngonyani, Kapella, Nyaga, Charles, Ruta, Happiness, Urassa, Mark, Akanyihayo, James, Arinaitwe, Arnold, Batuuka, Jesca, Birungi, Walusimbi, Bugembe, John Nyanzi, Ddungu, Ahmed, Francis, Kato, Imran, Bangira, Kafuuma, George William, Kalulue, John Bosco, Kanaabi, Grace, Kanyesigye, Michale, Karuhanga, Godfery, Kasozi, Charles, Kasule, Godfrey, Katusime, Assumpta, Kibalama, Donozio, Kimera, Simon Peter, Kulusumu, Namatovu, Lule, Yusuf, Lwanga, Isaac, Mluindwa, Margaret, Moses, Jemba, Mubarak, Sseremba, Muggaga, Daniel, Mukalazi, Evelyn, Muleebwa, Joseph, Mulema, Derick, Musisi, Ivan, Muwawu, John, Muyindike, Winnie, Mwaka, Dick, Naava, Milly, Nabiyki, Immaculate, Nabusulwa, Agnes, Nakabugo, Dorah, Nakamya, Esther, Nakanwagi, Daisy, Nakato, Oliver, Nakayi, Lydian, Nakigozi, Patience, Nakku, Juliet, Nakuya, Juliet, Nakyomu, Justine, Namayanja, Joan, Namirembe, Sarah, Namugumya, Juliet, Namukasa, Ezereth, Namulindwa, Viola, Nankya, Irene, Nannyondo, Grace Mugagga, Nansamba, Harriet, Nansera, Denis, Nanyanzi, Brenda, Nanyonjo, Esther Celina, Nayiga, Irene, Opira, Isaac, Owarwo, Noela C., Resty, Sserunkuma, Semuwemba, Haruna, Senoga, Julius, Sseguya, Gerald, Ssekyewa, John Paul, Ssemakadde, Matthew, Tebajjwa, Jonah, Tugumisirize, Doreen, Tushemerirwe, Robinah, Waliyi, Kawuki, Althoff, Keri, Bishop, Jennifer, Gill, M J., Loutfy, Mona, Smith, Graham, Bamford, Laura, Black, Anthony, Brice, Asia, Brown, Sheldon, Colasanti, Jonathan, Duarte, Piper, Firnhaber, Cynthia, Goetz, Matthew, Grasso, Chris, Gripshover, Barbara, Horberg, Michael, Kelly, Rita, Levine, Ken, Luu, Mitchell, Marconi, Vincent, Maroney, Karen, Mayer, Kenneth, Mayor, Angel, Mcgowan, Catherine, Multani, Ami, Napravnik, Sonia, Nijhawan, Ank, Novak, Richard, Palella, Frank, Rodriguez, Maria C., Scott, Mia, Tedaldi, Ellen, Willig, James, Cornell, Morna, Davies, Mary?Ann, Egger, Matthias, Haas, Andreas, Bereng, Monkoe, Kalake, Maleshoane, Lenela, Keketso, Seretse, Relebohile, Chintenga, Matthews, Chiwoko, Jane, Gumulira, Joe, Huwa, Jacqueline, Maluwa, Rafique, Matanje, Beatrice, Mbewe, Ronald, Mfungwe, Sunshine, Mphande, Zakaliah, Tweya, Hannock, Rafael, Idiovino, Apolles, Patti, Beneke, Eunice, Dlamini, Siphephelo, Edson, Claire, Eley, Brian, Euvrard, Jonathan, Fatti, Geoffrey, Goeieman, Bridgette, Grimwood, Ashraf, Huang, David, Hugo, Susan, Ismail, Zahiera, Jennings, Lauren, Mathenjwa, Thulile, Monteith, Lizette, Mshweshwe, Zamuxolo, Ntuli, Mfundi, Ndlovu, En, Ndlozi, Hloniphile, Noyakaza, Sylvia, Prozesky, Hans, Rabie, Helena, Sipambo, Nosisa, Technau, Karl?Günter, Tembe, Thokozani, Xaba, Nontando, Njobvu, Thandiwe, Munthaly, Mary, Mwetwa, Elly, Kabeba, Gillian, Mwendafilumba, Derrick, Maanguka, Ethel, Manyika, Nelly, Mwansa, Chalwe, Banda, Future, Mwenda, Dickson, Bwalya, Abel, Shapi, Leah, Syame, Kasapo, Sashi, Rita, Mulenga, Chisha, Nanyangwe, Ruth, Chimbetete, Cleophas, Chinofunga, A., Mhike, J., Mubvigwi, E., Nyika, F., Quarter, Kumbirai Pise, Arikawa, Shino Chassagne, Becquet, Renaud, Bernard, Charlotte, Dabis, François, Desmonde, Sophie, Dahourou, Désiré, Ekouevi, Didier Koumavi, Jaquet, Antoine, Jesson, Julie, Leroy, Valeriane, Malateste, Karen, Rabourdin, Elodie, Tiendrebeogo, Thierry, Assogba, Michée, Zannou, Djimon Marcel, Hounhoui, Ghislaine, Bere, Denise, Poda, Armel, Pooda, Gbolo, Traore, Richard, Abauble, Yao, Abby, Ouattara, Acquah, Patrick, Andoble, Valérie, Aude, Yobo N'Dzama, Azani, Jean?Claude, Berete, Oka, Beugre, Jacques Daple, Bohoussou, Caroline Yao, Brou, Simon Boni Emmanuel, Chenal, Henri, Cissé, Abdoulaye, Coulibaly, Nambate, Dainguy, Marie Evelyne, Daligou, Marcelle, D' Aquin, Toni Thomas, Dasse, Claude Desire, Folquet, Madeleine Amorissani, Gnepa, Guy, Gobe, Olivier, Guira, Salif, Hawerlander, Denise, Horo, Apollinaire, Kanga, Guillaume, Messou, Zobo Konan Eugène, Minga, Kla Albert, Moh, Raoul, N'Gbeche, Mariesylvie, Ogbo, Patricia, Oulai, Mathieu, Stéphanie, Se, Eboua, Tanoh, Valère, Itchy Max, Afrane, Adwoa Kumiwa Asare, Akrofi, Esther, Andoh, John Christian, Renner, Lorna, Bagayoko, Awa, Bagayoko, Kadidiatou, Bah, Abdou Salam, Berthe, Alima, Coulibaly, Boureïma, Coulibaly, Fatimata, Coulibaly, Yacouba Aba, Diakité, Aïssata, Bocoum, Fatoumata, Boré, Fatoumata, Dicko, Fatoumata, Koné, Odile, Sylla, Mariam, Tangara, Assitan, Traoré, Mamadou, Seydi, Moussa, Amegatse, Edmond, Djossou, Julienne, Takassi, Elom, and Palanga, Sénam

Subjects
HIV (Viruses) -- Care and treatment -- Patient outcomes, Public health administration -- Evaluation, Health
Abstract

: Introduction: Interruptions in treatment pose risks for people with HIV (PWH) and threaten progress in ending the HIV epidemic; however, the COVID‐19 pandemic's impact on HIV service delivery across diverse settings is not broadly documented. Methods: From September 2020 to March 2021, the International epidemiology Databases to Evaluate AIDS (IeDEA) research consortium surveyed 238 HIV care sites across seven geographic regions to document constraints in HIV service delivery during the first year of the pandemic and strategies for ensuring care continuity for PWH. Descriptive statistics were stratified by national HIV prevalence ( Results: Questions about pandemic‐related consequences for HIV care were completed by 225 (95%) sites in 42 countries with low (n = 82), medium (n = 86) and high (n = 57) HIV prevalence, including low‐ (n = 57), lower‐middle (n = 79), upper‐middle (n = 39) and high‐ (n = 50) income countries. Most sites reported being subject to pandemic‐related restrictions on travel, service provision or other operations (75%), and experiencing negative impacts (76%) on clinic operations, including decreased hours/days, reduced provider availability, clinic reconfiguration for COVID‐19 services, record‐keeping interruptions and suspension of partner support. Almost all sites in low‐prevalence and high‐income countries reported increased use of telemedicine (85% and 100%, respectively), compared with less than half of sites in high‐prevalence and lower‐income settings. Few sites in high‐prevalence settings (2%) reported suspending antiretroviral therapy (ART) clinic services, and many reported adopting mitigation strategies to support adherence, including multi‐month dispensing of ART (95%) and designating community ART pick‐up points (44%). While few sites (5%) reported stockouts of first‐line ART regimens, 10–11% reported stockouts of second‐ and third‐line regimens, respectively, primarily in high‐prevalence and lower‐income settings. Interruptions in HIV viral load (VL) testing included suspension of testing (22%), longer turnaround times (41%) and supply/reagent stockouts (22%), but did not differ across settings. Conclusions: While many sites in high HIV prevalence settings and lower‐income countries reported introducing or expanding measures to support treatment adherence and continuity of care, the COVID‐19 pandemic resulted in disruptions to VL testing and ART supply chains that may negatively affect the quality of HIV care in these settings., INTRODUCTION The COVID‐19 pandemic has had major direct and indirect impacts on population health globally, through disruptions in the accessibility and quality of basic health services [1], in supply chains [...]

Published
2022
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47. Cost-effectiveness of statins for primary prevention of atherosclerotic cardiovascular disease among people living with HIV in the United States

Author

Boettiger, David C., Newall, Anthony T., Phillips, Andrew, Bendavid, Eran, Law, Matthew G., Ryom, Lene, Reiss, Peter, Mocroft, Amanda, Bonnet, Fabrice, Weber, Rainer, El-Sadr, Wafaa, Monforte, Antonella D'Arminio, Dewit, Stephane, Pradier, Christian, Hatleberg, Camilla I., Lundgren, Jens, Sabin, Caroline, Kahn, James G., and Kazi, Dhruv S.

Subjects
Medical care, Cost of -- Statistics, HIV patients -- Drug therapy -- Statistics, Pravastatin -- Usage -- Economic aspects -- Statistics, Atherosclerosis -- Prevention, Health
Abstract

Background: Expanding statin use may help to alleviate the excess burden of atherosclerotic cardiovascular disease in people iving with HIV (PLHIV). Pravastatin and pitavastatin are preferred agents due to their lack of substantial interaction with antiretroviral therapy. We aimed to evaluate the cost-effectiveness of pravastatin and pitavastatin for the primary prevention of atherosclerotic cardiovascular disease among PLHIV in the United States. Methods: We developed a microsimulation model that randomly selected (with replacement) individuals from the Data-collection on Adverse Effects of Anti-HIV Drugs study with follow-up between 2013 and 2016. Our study population was PLHIV aged 40 to 75 years, stable on antiretroviral therapy and not currently using lipid-lowering therapy. Direct medical costs and quality-adjusted life-years (QALYs) were assigned in annual cycles and discounted at 3% per year. We assumed a willingness-to-pay threshold of $100,000/QALY gained. The interventions assessed were as follows: (1) treating no one with statins; (2) treating everyone with generic pravastatin 40 mg/day (drug cost $236/year) and (3) treating everyone with branded pitavastatin 4 mg/day (drug cost $2,828/year). The model simulated each individual's probability of experiencing atherosclerotic cardiovascular disease over 20 years. Results: Persons receiving pravastatin accrued 0.024 additional QALYs compared with those not receiving a statin, at an incremental cost of $1338, giving an incremental cost-effectiveness ratio of $56,000/QALY gained. Individuals receiving pitavastatin accumulated 0.013 additional QALYs compared with those using pravastatin, at an additional cost of $18,251, giving an incremental cost-effectiveness ratio of $1,444,000/QALY gained. These findings were most sensitive to the pill burden associated with daily statin administration, statin costs, statin efficacy and baseline atherosclerotic cardiovascular disease risk. In probabilistic sensitivity analysis, no statin was optimal in 5.2% of simulations, pravastatin was optimal in 94.8% of simulations and pitavastatin was never optimal. Conclusions: Pravastatin was projected to be cost-effective compared with no statin. With substantial price reduction, pitavastatin may be cost-effective compared with pravastatin. These findings bode well for the expanded use of statins among PLHIV in the United States. To gain greater confidence in our conclusions it is important to generate strong, HIV-specific estimates on the efficacy of statins and the quality-of-life burden associated with taking an additional daily pill. Keywords: HIV; cardiovascular disease; statin; cost-effectiveness; United States; antiretroviral therapy Received 4 September 2020; Accepted 23 February 2021, 1 | INTRODUCTION People living with HIV (PLHIV) have an elevated risk of atherosclerotic cardiovascular disease (ASCVD) compared to people without HIV [1]. This is only partially explained by the [...]

Published
2021
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48. Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study

Author

Haycock, Philip C, Burgess, Stephen, Nounu, Aayah, Zheng, Jie, Okoli, George N, Bowden, Jack, Wade, Kaitlin Hazel, Timpson, Nicholas J, Evans, David M, Willeit, Peter, Aviv, Abraham, Gaunt, Tom R, Hemani, Gibran, Mangino, Massimo, Ellis, Hayley Patricia, Kurian, Kathreena M, Pooley, Karen A, Eeles, Rosalind A, Lee, Jeffrey E, Fang, Shenying, Chen, Wei V, Law, Matthew H, Bowdler, Lisa M, Iles, Mark M, Yang, Qiong, Worrall, Bradford B, Markus, Hugh Stephen, Hung, Rayjean J, Amos, Chris I, Spurdle, Amanda B, Thompson, Deborah J, O’Mara, Tracy A, Wolpin, Brian, Amundadottir, Laufey, Stolzenberg-Solomon, Rachael, Trichopoulou, Antonia, Onland-Moret, N Charlotte, Lund, Eiliv, Duell, Eric J, Canzian, Federico, Severi, Gianluca, Overvad, Kim, Gunter, Marc J, Tumino, Rosario, Svenson, Ulrika, van Rij, Andre, Baas, Annette F, Bown, Matthew J, Samani, Nilesh J, van t’Hof, Femke NG, Tromp, Gerard, Jones, Gregory T, Kuivaniemi, Helena, Elmore, James R, Johansson, Mattias, Mckay, James, Scelo, Ghislaine, Carreras-Torres, Robert, Gaborieau, Valerie, Brennan, Paul, Bracci, Paige M, Neale, Rachel E, Olson, Sara H, Gallinger, Steven, Li, Donghui, Petersen, Gloria M, Risch, Harvey A, Klein, Alison P, Han, Jiali, Abnet, Christian C, Freedman, Neal D, Taylor, Philip R, Maris, John M, Aben, Katja K, Kiemeney, Lambertus A, Vermeulen, Sita H, Wiencke, John K, Walsh, Kyle M, Wrensch, Margaret, Rice, Terri, Turnbull, Clare, Litchfield, Kevin, Paternoster, Lavinia, Standl, Marie, Abecasis, Gonçalo R, SanGiovanni, John Paul, Li, Yong, Mijatovic, Vladan, Sapkota, Yadav, Low, Siew-Kee, Zondervan, Krina T, Montgomery, Grant W, Nyholt, Dale R, van Heel, David A, Hunt, Karen, Arking, Dan E, Ashar, Foram N, Sotoodehnia, Nona, Woo, Daniel, and Rosand, Jonathan

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Rare Diseases, Clinical Research, Cancer, Prevention, Genetics, Aetiology, 2.1 Biological and endogenous factors, Adult, Aged, Aged, 80 and over, Cardiovascular Diseases, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Germ-Line Mutation, Humans, Male, Mendelian Randomization Analysis, Middle Aged, Neoplasms, Polymorphism, Single Nucleotide, Risk Assessment, Telomere, Telomere Homeostasis, Telomeres Mendelian Randomization Collaboration, Public Health and Health Services, Oncology and carcinogenesis
Abstract

ImportanceThe causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation.ObjectiveTo conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases.Data sourcesGenomewide association studies (GWAS) published up to January 15, 2015.Study selectionGWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available.Data extraction and synthesisSummary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population.Main outcomes and measuresOdds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation.ResultsSummary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [95% CI, 0.05-0.15]).Conclusions and relevanceIt is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.

Published
2017

49. Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study.

Author

Telomeres Mendelian Randomization Collaboration, Haycock, Philip C, Burgess, Stephen, Nounu, Aayah, Zheng, Jie, Okoli, George N, Bowden, Jack, Wade, Kaitlin Hazel, Timpson, Nicholas J, Evans, David M, Willeit, Peter, Aviv, Abraham, Gaunt, Tom R, Hemani, Gibran, Mangino, Massimo, Ellis, Hayley Patricia, Kurian, Kathreena M, Pooley, Karen A, Eeles, Rosalind A, Lee, Jeffrey E, Fang, Shenying, Chen, Wei V, Law, Matthew H, Bowdler, Lisa M, Iles, Mark M, Yang, Qiong, Worrall, Bradford B, Markus, Hugh Stephen, Hung, Rayjean J, Amos, Chris I, Spurdle, Amanda B, Thompson, Deborah J, O'Mara, Tracy A, Wolpin, Brian, Amundadottir, Laufey, Stolzenberg-Solomon, Rachael, Trichopoulou, Antonia, Onland-Moret, N Charlotte, Lund, Eiliv, Duell, Eric J, Canzian, Federico, Severi, Gianluca, Overvad, Kim, Gunter, Marc J, Tumino, Rosario, Svenson, Ulrika, van Rij, Andre, Baas, Annette F, Bown, Matthew J, Samani, Nilesh J, van t'Hof, Femke NG, Tromp, Gerard, Jones, Gregory T, Kuivaniemi, Helena, Elmore, James R, Johansson, Mattias, Mckay, James, Scelo, Ghislaine, Carreras-Torres, Robert, Gaborieau, Valerie, Brennan, Paul, Bracci, Paige M, Neale, Rachel E, Olson, Sara H, Gallinger, Steven, Li, Donghui, Petersen, Gloria M, Risch, Harvey A, Klein, Alison P, Han, Jiali, Abnet, Christian C, Freedman, Neal D, Taylor, Philip R, Maris, John M, Aben, Katja K, Kiemeney, Lambertus A, Vermeulen, Sita H, Wiencke, John K, Walsh, Kyle M, Wrensch, Margaret, Rice, Terri, Turnbull, Clare, Litchfield, Kevin, Paternoster, Lavinia, Standl, Marie, Abecasis, Gonçalo R, SanGiovanni, John Paul, Li, Yong, Mijatovic, Vladan, Sapkota, Yadav, Low, Siew-Kee, Zondervan, Krina T, Montgomery, Grant W, Nyholt, Dale R, van Heel, David A, Hunt, Karen, Arking, Dan E, Ashar, Foram N, Sotoodehnia, Nona, and Woo, Daniel

Subjects
Telomeres Mendelian Randomization Collaboration, Telomere, Humans, Neoplasms, Cardiovascular Diseases, Genetic Predisposition to Disease, Risk Assessment, Germ-Line Mutation, Polymorphism, Single Nucleotide, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Genome-Wide Association Study, Mendelian Randomization Analysis, Telomere Homeostasis, Polymorphism, Single Nucleotide, and over, Prevention, Clinical Research, Cancer, Genetics, Rare Diseases, 2.1 Biological and endogenous factors, Oncology and Carcinogenesis, Public Health and Health Services
Abstract

ImportanceThe causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation.ObjectiveTo conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases.Data sourcesGenomewide association studies (GWAS) published up to January 15, 2015.Study selectionGWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available.Data extraction and synthesisSummary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population.Main outcomes and measuresOdds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation.ResultsSummary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [95% CI, 0.05-0.15]).Conclusions and relevanceIt is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.

Published
2017

50. Virological failure and treatment switch after ART initiation among people living with HIV with and without routine viral load monitoring in Asia

Author

Teeraananchai, Sirinya, Law, Matthew, Boettiger, David, De La Mata, Nicole, Gupte, Nikhil, Chan, Yun?Ting Lawrence, Pham, Thach Ngoc, Chaiwarith, Romanee, Ly, Penh Sun, Chan, Yu?Jiun, Kiertiburanakul, Sasisopin, Khusuwan, Suwimon, Zhang, Fujie, Yunihastuti, Evy, Kumarasamy, Nagalingeswaran, Pujari, Sanjay, Azwa, Iskandar, Somia, I Ketut Agus, Tanuma, Junko, Ditangco, Rossana, Choi, Jun Yong, Ng, Oon Tek, Do, Cuong Duy, Gani, Yasmin, Ross, Jeremy, and Jiamsakul, Awachana

Subjects
Viremia -- Measurement, Highly active antiretroviral therapy -- Methods, HIV patients -- Evaluation, HIV infection -- Prevention -- Care and treatment, Health
Abstract

: Introduction: Viral load (VL) testing is still challenging to monitor treatment responses of antiretroviral therapy (ART) for HIV treatment programme in Asia. We assessed the association between routine VL testing and virological failure (VF) and determine factors associated with switching to second‐line regimen. Methods: Among 21 sites from the TREAT Asia HIV Observational Database (TAHOD), people living with HIV (PLHIV) aged ≥18 years initiating ART from 2003 to 2021 were included. We calculated the average number of VL tests per patient per year between the date of ART initiation and the most recent visit. If the median average number of VL tests was ≥ 0.80 per patient per year, the site was classified as a routine VL site. A site with a median < 0.80 was classified into the non‐routine VL sites. VF was defined as VL ≥1000 copies/ml during first‐line therapy. Factors associated with VF were analysed using generalized estimating equations with Poisson distribution. Results: Of 6277 PLHIV starting ART after 2003, 3030 (48%) were from 11 routine VL testing sites and 3247 (52%) were from 10 non‐routine VL testing sites. The median follow‐up was 9 years (IQR 5–13). The median age was 35 (30–42) years; 68% were male and 5729 (91%) started non‐nucleoside reverse‐transcriptase inhibitor‐based regimen. The median pre‐ART CD4 count in PLHIV from routine VL sites was lower compared to non‐routine VL sites (144 vs. 156 cells/mm[sup.3], p Conclusions: PLHIV from non‐routine VL sites had a higher incidence of persistent VF and a low switching regimen rate, reflecting possible under‐utilized VL testing., INTRODUCTION The scale‐up of antiretroviral therapy (ART) had a substantial positive impact on the health and quality of life of people living with HIV (PLHIV) and significantly reduced the incidence [...]

Published
2022
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