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1. RACCOON: A Retrieval-Augmented Generation Approach for Location Coordinate Capture from News Articles

Author

Lin, Jonathan, Joshi, Aditya, Paik, Hye-young, Doung, Tri Dung, and Gurdasani, Deepti

Subjects
Computer Science - Computation and Language
Abstract

Geocoding involves automatic extraction of location coordinates of incidents reported in news articles, and can be used for epidemic intelligence or disaster management. This paper introduces Retrieval-Augmented Coordinate Capture Of Online News articles (RACCOON), an open-source geocoding approach that extracts geolocations from news articles. RACCOON uses a retrieval-augmented generation (RAG) approach where candidate locations and associated information are retrieved in the form of context from a location database, and a prompt containing the retrieved context, location mentions and news articles is fed to an LLM to generate the location coordinates. Our evaluation on three datasets, two underlying LLMs, three baselines and several ablation tests based on the components of RACCOON demonstrate the utility of RACCOON. To the best of our knowledge, RACCOON is the first RAG-based approach for geocoding using pre-trained LLMs., Comment: Accepted at WWW 2025 as a short paper. 4 pages with references

Published
2025

2. High-resolution African HLA resource uncovers HLA-DRB1 expression effects underlying vaccine response.

Author

Mentzer, Alexander, Dilthey, Alexander, Pollard, Martin, Gurdasani, Deepti, Karakoc, Emre, Carstensen, Tommy, Muhwezi, Allan, Cutland, Clare, Diarra, Amidou, da Silva Antunes, Ricardo, Paul, Sinu, Smits, Gaby, Wareing, Susan, Kim, HwaRan, Pomilla, Cristina, Chong, Amanda, Brandt, Debora, Neaves, Samuel, Timpson, Nicolas, Crinklaw, Austin, Lindestam Arlehamn, Cecilia, Rautanen, Anna, Kizito, Dennison, Parks, Tom, Auckland, Kathryn, Elliott, Kate, Mills, Tara, Ewer, Katie, Edwards, Nick, Fatumo, Segun, Webb, Emily, Peacock, Sarah, Jeffery, Katie, van der Klis, Fiona, Kaleebu, Pontiano, Vijayanand, Pandurangan, Peters, Bjorn, Sette, Alessandro, Cereb, Nezih, Sirima, Sodiomon, Madhi, Shabir, Elliott, Alison, McVean, Gil, Hill, Adrian, Sandhu, Manjinder, and Nielsen, Rasmus

Subjects
Humans, HLA-DRB1 Chains, Infant, Black People, Hepatitis B Vaccines, Quantitative Trait Loci, Male, Female, Uganda, Antibody Formation, Pertussis Vaccine, Vaccination, Whooping Cough
Abstract

How human genetic variation contributes to vaccine effectiveness in infants is unclear, and data are limited on these relationships in populations with African ancestries. We undertook genetic analyses of vaccine antibody responses in infants from Uganda (n = 1391), Burkina Faso (n = 353) and South Africa (n = 755), identifying associations between human leukocyte antigen (HLA) and antibody response for five of eight tested antigens spanning pertussis, diphtheria and hepatitis B vaccines. In addition, through HLA typing 1,702 individuals from 11 populations of African ancestry derived predominantly from the 1000 Genomes Project, we constructed an imputation resource, fine-mapping class II HLA-DR and DQ associations explaining up to 10% of antibody response variance in our infant cohorts. We observed differences in the genetic architecture of pertussis antibody response between the cohorts with African ancestries and an independent cohort with European ancestry, but found no in silico evidence of differences in HLA peptide binding affinity or breadth. Using immune cell expression quantitative trait loci datasets derived from African-ancestry samples from the 1000 Genomes Project, we found evidence of differential HLA-DRB1 expression correlating with inferred protection from pertussis following vaccination. This work suggests that HLA-DRB1 expression may play a role in vaccine response and should be considered alongside peptide selection to improve vaccine design.

Published
2024

3. Relation Extraction from News Articles (RENA): A Tool for Epidemic Surveillance

Author

Hong, Jaeff, Dung, Duong, Hutchinson, Danielle, Akhtar, Zubair, Chen, Rosalie, Dawson, Rebecca, Joshi, Aditya, Lim, Samsung, MacIntyre, C Raina, and Gurdasani, Deepti

Subjects
Computer Science - Computation and Language, Computer Science - Artificial Intelligence
Abstract

Relation Extraction from News Articles (RENA) is a browser-based tool designed to extract key entities and their semantic relationships in English language news articles related to infectious diseases. Constructed using the React framework, this system presents users with an elegant and user-friendly interface. It enables users to input a news article and select from a choice of two models to generate a comprehensive list of relations within the provided text. As a result, RENA allows real-time parsing of news articles to extract key information for epidemic surveillance, contributing to EPIWATCH, an open-source intelligence-based epidemic warning system., Comment: Under review in AAAI 2024

Published
2023

4. Classification of genetic variants using machine learning

Author

Jain, Abhinav, Slabaugh, Greg, and Gurdasani, Deepti

Subjects
Quantitative Biology - Genomics, I.5.1
Abstract

Recent advances in genomic sequencing technology have resulted in an abundance of genome sequence data. Despite the progress in interpreting those data, there remains a broad scope for their translation into clinical and societal benefits. Loss-of-function variations in the human genome can be causal in disease development. Precise identification of such variations and pathogenicity prediction may lead to better drug targeting, among other benefits. Machine learning comes across as a promising method for its proven predictive ability. We have curated a novel dataset for the classification of LOF variants using high-quality databases of genetic variation. We trained and validated seven different classification algorithms using the new dataset to classify the variants as Benign, Pathogenic and Likely pathogenic. We recorded the best overall performance using the XG-Boost algorithm with an F1-score of 0.88 on the test set. We observed fair performance on Pathogenic samples with high recall and moderate precision and subpar performance on Likely pathogenic class, albeit with moderate precision. Overall, the encouraging results make our final model a promising candidate for further real-world tests., Comment: 9 pages, 11 figures

Published
2021

6. Africa-specific human genetic variation near CHD1L associates with HIV-1 load

Author

McLaren, Paul J., Porreca, Immacolata, Iaconis, Gennaro, Mok, Hoi Ping, Mukhopadhyay, Subhankar, Karakoc, Emre, Cristinelli, Sara, Pomilla, Cristina, Bartha, István, Thorball, Christian W., Tough, Riley H., Angelino, Paolo, Kiar, Cher S., Carstensen, Tommy, Fatumo, Segun, Porter, Tarryn, Jarvis, Isobel, Skarnes, William C., Bassett, Andrew, DeGorter, Marianne K., Sathya Moorthy, Mohana Prasad, Tuff, Jeffrey F., Kim, Eun-Young, Walter, Miriam, Simons, Lacy M., Bashirova, Arman, Buchbinder, Susan, Carrington, Mary, Cossarizza, Andrea, De Luca, Andrea, Goedert, James J., Goldstein, David B., Haas, David W., Herbeck, Joshua T., Johnson, Eric O., Kaleebu, Pontiano, Kilembe, William, Kirk, Gregory D., Kootstra, Neeltje A., Kral, Alex H., Lambotte, Olivier, Luo, Ma, Mallal, Simon, Martinez-Picado, Javier, Meyer, Laurence, Miro, José M., Moodley, Pravi, Motala, Ayesha A., Mullins, James I., Nam, Kireem, Obel, Niels, Pirie, Fraser, Plummer, Francis A., Poli, Guido, Price, Matthew A., Rauch, Andri, Theodorou, Ioannis, Trkola, Alexandra, Walker, Bruce D., Winkler, Cheryl A., Zagury, Jean-François, Montgomery, Stephen B., Ciuffi, Angela, Hultquist, Judd F., Wolinsky, Steven M., Dougan, Gordon, Lever, Andrew M. L., Gurdasani, Deepti, Groom, Harriet, Sandhu, Manjinder S., and Fellay, Jacques

Published
2023
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8. COVID-19 trajectories among 57 million adults in England: a cohort study using electronic health records

Author

Abbasizanjani, Hoda, Ahmed, Nida, Ahmed, Badar, Akbari, Ashley, Akinoso-Imran, Abdul Qadr, Allara, Elias, Allery, Freya, Angelantonio, Emanuele Di, Ashworth, Mark, Ayyar-Gupta, Vandana, Babu-Narayan, Sonya, Bacon, Seb, Ball, Steve, Banerjee, Ami, Barber, Mark, Barrett, Jessica, Bennie, Marion, Berry, Colin, Beveridge, Jennifer, Birney, Ewan, Bojanić, Lana, Bolton, Thomas, Bone, Anna, Boyle, Jon, Braithwaite, Tasanee, Bray, Ben, Briffa, Norman, Brind, David, Brown, Katherine, Buch, Maya, Canoy, Dexter, Caputo, Massimo, Carragher, Raymond, Carson, Alan, Cezard, Genevieve, Chang, Jen-Yu Amy, Cheema, Kate, Chin, Richard, Chudasama, Yogini, Cooper, Jennifer, Copland, Emma, Crallan, Rebecca, Cripps, Rachel, Cromwell, David, Curcin, Vasa, Curry, Gwenetta, Dale, Caroline, Danesh, John, Das-Munshi, Jayati, Dashtban, Ashkan, Davies, Alun, Davies, Joanna, Davies, Gareth, Davies, Neil, Day, Joshua, Delmestri, Antonella, Denaxas, Spiros, Denholm, Rachel, Dennis, John, Denniston, Alastair, Deo, Salil, Dhillon, Baljean, Docherty, Annemarie, Dong, Tim, Douiri, Abdel, Downs, Johnny, Dregan, Alexandru, Ellins, Elizabeth A, Elwenspoek, Martha, Falck, Fabian, Falter, Florian, Fan, Yat Yi, Firth, Joseph, Fraser, Lorna, Friebel, Rocco, Gavrieli, Amir, Gerstung, Moritz, Gilbert, Ruth, Gillies, Clare, Glickman, Myer, Goldacre, Ben, Goldacre, Raph, Greaves, Felix, Green, Mark, Grieco, Luca, Griffiths, Rowena, Gurdasani, Deepti, Halcox, Julian, Hall, Nick, Hama, Tuankasfee, Handy, Alex, Hansell, Anna, Hardelid, Pia, Hardy, Flavien, Harris, Daniel, Harrison, Camille, Harron, Katie, Hassaine, Abdelaali, Hassan, Lamiece, Healey, Russell, Hemingway, Harry, Henderson, Angela, Herz, Naomi, Heyl, Johannes, Hidajat, Mira, Higginson, Irene, Hinchliffe, Rosie, Hippisley-Cox, Julia, Ho, Frederick, Hocaoglu, Mevhibe, Hollings, Sam, Horne, Elsie, Hughes, David, Humberstone, Ben, Inouye, Mike, Ip, Samantha, Islam, Nazrul, Jackson, Caroline, Jenkins, David, Jiang, Xiyun, Johnson, Shane, Kadam, Umesh, Kallis, Costas, Karim, Zainab, Kasan, Jake, Katsoulis, Michalis, Kavanagh, Kim, Kee, Frank, Keene, Spencer, Kent, Seamus, Khalid, Sara, Khawaja, Anthony, Khunti, Kamlesh, Killick, Richard, Kinnear, Deborah, Knight, Rochelle, Kolamunnage-Dona, Ruwanthi, Kontopantelis, Evan, Kurdi, Amanj, Lacey, Ben, Lai, Alvina, Lambarth, Andrew, Larzjan, Milad Nazarzadeh, Lawler, Deborah, Lawrence, Thomas, Lawson, Claire, Li, Qiuju, Li, Ken, Llinares, Miguel Bernabeu, Lorgelly, Paula, Lowe, Deborah, Lyons, Jane, Lyons, Ronan, Machado, Pedro, Macleod, Mary Joan, Macleod, John, Malgapo, Evaleen, Mamas, Mamas, Mamouei, Mohammad, Manohar, Sinduja, Mapeta, Rutendo, Martelli, Javiera Leniz, Martos, David Moreno, Mateen, Bilal, McCarthy, Aoife, Melville, Craig, Milton, Rebecca, Mizani, Mehrdad, Moncusi, Marta Pineda, Morales, Daniel, Mordi, Ify, Morrice, Lynn, Morris, Carole, Morris, Eva, Mu, Yi, Mueller, Tanja, Murdock, Lars, Nafilyan, Vahé, Nicholson, George, Nikiphorou, Elena, Nolan, John, Norris, Tom, Norris, Ruth, North, Laura, North, Teri-Louise, O'Connell, Dan, Oliver, Dominic, Oluyase, Adejoke, Olvera-Barrios, Abraham, Omigie, Efosa, Onida, Sarah, Padmanabhan, Sandosh, Palmer, Tom, Pasea, Laura, Patel, Riyaz, Payne, Rupert, Pell, Jill, Petitjean, Carmen, Pherwani, Arun, Pickrell, Owen, Pierotti, Livia, Pirmohamed, Munir, Priedon, Rouven, Prieto-Alhambra, Dani, Proudfoot, Alastair, Quinn, Terry, Quint, Jennifer, Raffetti, Elena, Rahimi, Kazem, Rao, Shishir, Razieh, Cameron, Roberts, Brian, Rogers, Caroline, Rossdale, Jennifer, Salim, Safa, Samani, Nilesh, Sattar, Naveed, Schnier, Christian, Schwartz, Roy, Selby, David, Seminog, Olena, Shabnam, Sharmin, Shah, Ajay, Shelton, Jon, Sheppard, James, Sinha, Shubhra, Skrypak, Mirek, Slapkova, Martina, Sleeman, Katherine, Smith, Craig, Sofat, Reecha, Sosenko, Filip, Sperrin, Matthew, Steeg, Sarah, Sterne, Jonathan, Stoica, Serban, Sudell, Maria, Sudlow, Cathie, Sun, Luanluan, Suseeladevi, Arun Karthikeyan, Sweeting, Michael, Sydes, Matt, Takhar, Rohan, Tang, Howard, Thygesen, Johan, Tilston, George, Tochel, Claire, Toit, Clea du, Tomlinson, Christopher, Toms, Renin, Torabi, Fatemeh, Torralbo, Ana, Townson, Julia, Tufail, Adnan, Tungamirai, Tapiwa, Varma, Susheel, Vollmer, Sebastian, Walker, Venexia, Wang, Tianxiao, Wang, Huan, Warwick, Alasdair, Watkinson, Ruth, Watson, Harry, Whiteley, William, Whittaker, Hannah, Wilde, Harry, Wilkinson, Tim, Williams, Gareth, Williams, Michelle, Williams, Richard, Withnell, Eloise, Wolfe, Charles, Wood, Angela, Wright, Lucy, Wu, Honghan, Wu, Jinge, Wu, Jianhua, Yates, Tom, Zaccardi, Francesco, Zhang, Haoting, Zhang, Huayu, Zuccolo, Luisa, Thygesen, Johan H, Mizani, Mehrdad A, Banerjee, Amitava, Lai, Alvina G, Li, Kezhi, Mateen, Bilal A, Sterne, Jonathan A C, Pagel, Christina, and Whiteley, William N

Published
2022
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9. Author Correction: Africa-specific human genetic variation near CHD1L associates with HIV-1 load

Author

McLaren, Paul J., Porreca, Immacolata, Iaconis, Gennaro, Mok, Hoi Ping, Mukhopadhyay, Subhankar, Karakoc, Emre, Cristinelli, Sara, Pomilla, Cristina, Bartha, István, Thorball, Christian W., Tough, Riley H., Angelino, Paolo, Kiar, Cher S., Carstensen, Tommy, Fatumo, Segun, Porter, Tarryn, Jarvis, Isobel, Skarnes, William C., Bassett, Andrew, DeGorter, Marianne K., Sathya Moorthy, Mohana Prasad, Tuff, Jeffrey F., Kim, Eun-Young, Walter, Miriam, Simons, Lacy M., Bashirova, Arman, Buchbinder, Susan, Carrington, Mary, Cossarizza, Andrea, De Luca, Andrea, Goedert, James J., Goldstein, David B., Haas, David W., Herbeck, Joshua T., Johnson, Eric O., Kaleebu, Pontiano, Kilembe, William, Kirk, Gregory D., Kootstra, Neeltje A., Kral, Alex H., Lambotte, Olivier, Luo, Ma, Mallal, Simon, Martinez-Picado, Javier, Meyer, Laurence, Miro, José M., Moodley, Pravi, Motala, Ayesha A., Mullins, James I., Nam, Kireem, Obel, Niels, Pirie, Fraser, Plummer, Francis A., Poli, Guido, Price, Matthew A., Rauch, Andri, Theodorou, Ioannis, Trkola, Alexandra, Walker, Bruce D., Winkler, Cheryl A., Zagury, Jean-François, Montgomery, Stephen B., Ciuffi, Angela, Hultquist, Judd F., Wolinsky, Steven M., Dougan, Gordon, Lever, Andrew M. L., Gurdasani, Deepti, Groom, Harriet, Sandhu, Manjinder S., and Fellay, Jacques

Published
2023
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10. Insights into the genetic architecture of haematological traits from deep phenotyping and whole-genome sequencing for two Mediterranean isolated populations

Author

Kuchenbaecker, Karoline, Gilly, Arthur, Suveges, Daniel, Southam, Lorraine, Giannakopoulou, Olga, Kilian, Britt, Tsafantakis, Emmanouil, Karaleftheri, Maria, Farmaki, Aliki-Eleni, Gurdasani, Deepti, Kundu, Kousik, Sandhu, Manjinder S., Danesh, John, Butterworth, Adam, Barroso, Inês, Dedoussis, George, and Zeggini, Eleftheria

Published
2022
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11. HIV treatment is associated with a two-fold higher probability of raised triglycerides: Pooled Analyses in 21 023 individuals in sub-Saharan Africa.

Author

Ekoru, Kenneth, Young, Elizabeth H, Dillon, David G, Gurdasani, Deepti, Stehouwer, Nathan, Faurholt-Jepsen, Daniel, Levitt, Naomi S, Crowther, Nigel J, Nyirenda, Moffat, Njelekela, Marina A, Ramaiya, Kaushik, Nyan, Ousman, Adewole, Olanisun O, Anastos, Kathryn, Compostella, Caterina, Dave, Joel A, Fourie, Carla M, Friis, Henrik, Kruger, Iolanthe M, Longenecker, Chris T, Maher, Dermot P, Mutimura, Eugene, Ndhlovu, Chiratidzo E, Praygod, George, Pefura Yone, Eric W, Pujades-Rodriguez, Mar, Range, Nyagosya, Sani, Mahmoud U, Sanusi, Muhammad, Schutte, Aletta E, Sliwa, Karen, Tien, Phyllis C, Vorster, Este H, Walsh, Corinna, Gareta, Dickman, Mashili, Fredirick, Sobngwi, Eugene, Adebamowo, Clement, Kamali, Anatoli, Seeley, Janet, Smeeth, Liam, Pillay, Deenan, Motala, Ayesha A, Kaleebu, Pontiano, and Sandhu, Manjinder S

Subjects
Antiretroviral therapy, Cardiovascular disease, HIV, Lipids, Sub-Saharan Africa, Triglycerides
Abstract

BackgroundAnti-retroviral therapy (ART) regimes for HIV are associated with raised levels of circulating triglycerides (TG) in western populations. However, there are limited data on the impact of ART on cardiometabolic risk in sub-Saharan African (SSA) populations.MethodsPooled analyses of 14 studies comprising 21 023 individuals, on whom relevant cardiometabolic risk factors (including TG), HIV and ART status were assessed between 2003 and 2014, in SSA. The association between ART and raised TG (>2.3 mmol/L) was analysed using regression models.FindingsAmong 10 615 individuals, ART was associated with a two-fold higher probability of raised TG (RR 2.05, 95% CI 1.51-2.77, I2=45.2%). The associations between ART and raised blood pressure, glucose, HbA1c, and other lipids were inconsistent across studies.InterpretationEvidence from this study confirms the association of ART with raised TG in SSA populations. Given the possible causal effect of raised TG on cardiovascular disease (CVD), the evidence highlights the need for prospective studies to clarify the impact of long term ART on CVD outcomes in SSA.

Published
2018

12. HIV treatment is associated with a twofold higher probability of raised triglycerides: pooled analyses in 21 023 individuals in sub-Saharan Africa

Author

Ekoru, Kenneth, Young, Elizabeth H, Dillon, David G, Gurdasani, Deepti, Stehouwer, Nathan, Faurholt-Jepsen, Daniel, Levitt, Naomi S, Crowther, Nigel J, Nyirenda, Moffat, Njelekela, Marina A, Ramaiya, Kaushik, Nyan, Ousman, Adewole, Olanisun O, Anastos, Kathryn, Compostella, Caterina, Dave, Joel A, Fourie, Carla M, Friis, Henrik, Kruger, Iolanthe M, Longenecker, Chris T, Maher, Dermot P, Mutimura, Eugene, Ndhlovu, Chiratidzo E, Praygod, George, Pefura Yone, Eric W, Pujades-Rodriguez, Mar, Range, Nyagosya, Sani, Mahmoud U, Sanusi, Muhammad, Schutte, Aletta E, Sliwa, Karen, Tien, Phyllis C, Vorster, Este H, Walsh, Corinna, Gareta, Dickman, Mashili, Fredirick, Sobngwi, Eugene, Adebamowo, Clement, Kamali, Anatoli, Seeley, Janet, Smeeth, Liam, Pillay, Deenan, Motala, Ayesha A, Kaleebu, Pontiano, and Sandhu, Manjinder S

Subjects
Public Health, Health Sciences, Prevention, Cardiovascular, Heart Disease, HIV/AIDS, Mental Health, Infectious Diseases, Good Health and Well Being, Antiretroviral therapy, cardiovascular disease, HIV, lipids, sub-Saharan Africa, triglycerides, Cardiovascular disease, Lipids, Sub-Saharan Africa, Triglycerides, Genetics, Epidemiology, Public health
Abstract

Anti-retroviral therapy (ART) regimes for HIV are associated with raised levels of circulating triglycerides (TG) in western populations. However, there are limited data on the impact of ART on cardiometabolic risk in sub-Saharan African (SSA) populations. Pooled analyses of 14 studies comprising 21 023 individuals, on whom relevant cardiometabolic risk factors (including TG), HIV and ART status were assessed between 2003 and 2014, in SSA. The association between ART and raised TG (>2.3 mmol/L) was analysed using regression models. Among 10 615 individuals, ART was associated with a two-fold higher probability of raised TG (RR 2.05, 95% CI 1.51-2.77, I2=45.2%). The associations between ART and raised blood pressure, glucose, HbA1c, and other lipids were inconsistent across studies. Evidence from this study confirms the association of ART with raised TG in SSA populations. Given the possible causal effect of raised TG on cardiovascular disease (CVD), the evidence highlights the need for prospective studies to clarify the impact of long term ART on CVD outcomes in SSA.

Published
2018

14. Uganda Genome Resource Enables Insights into Population History and Genomic Discovery in Africa

Author

Gurdasani, Deepti, Carstensen, Tommy, Fatumo, Segun, Chen, Guanjie, Franklin, Chris S., Prado-Martinez, Javier, Bouman, Heleen, Abascal, Federico, Haber, Marc, Tachmazidou, Ioanna, Mathieson, Iain, Ekoru, Kenneth, DeGorter, Marianne K., Nsubuga, Rebecca N., Finan, Chris, Wheeler, Eleanor, Chen, Li, Cooper, David N., Schiffels, Stephan, Chen, Yuan, Ritchie, Graham R.S., Pollard, Martin O., Fortune, Mary D., Mentzer, Alex J., Garrison, Erik, Bergström, Anders, Hatzikotoulas, Konstantinos, Adeyemo, Adebowale, Doumatey, Ayo, Elding, Heather, Wain, Louise V., Ehret, Georg, Auer, Paul L., Kooperberg, Charles L., Reiner, Alexander P., Franceschini, Nora, Maher, Dermot, Montgomery, Stephen B., Kadie, Carl, Widmer, Chris, Xue, Yali, Seeley, Janet, Asiki, Gershim, Kamali, Anatoli, Young, Elizabeth H., Pomilla, Cristina, Soranzo, Nicole, Zeggini, Eleftheria, Pirie, Fraser, Morris, Andrew P., Heckerman, David, Tyler-Smith, Chris, Motala, Ayesha A., Rotimi, Charles, Kaleebu, Pontiano, Barroso, Inês, and Sandhu, Manj S.

Published
2019
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17. A systematic review of definitions of extreme phenotypes of HIV control and progression.

Author

Gurdasani, Deepti, Iles, Louise, Dillon, David, Young, Elizabeth, Olson, Ashley, Naranbhai, Vivek, Fidler, Sarah, Gkrania-Klotsas, Effrossyni, Post, Frank, Kellam, Paul, Porter, Kholoud, and Sandhu, Manjinder

Subjects
Disease Progression, HIV Infections, HIV Long-Term Survivors, Humans, Phenotype, Terminology as Topic
Abstract

The study of individuals at opposite ends of the HIV clinical spectrum can provide invaluable insights into HIV biology. Heterogeneity in criteria used to define these individuals can introduce inconsistencies in results from research and make it difficult to identify biological mechanisms underlying these phenotypes. In this systematic review, we formally quantified the heterogeneity in definitions used for terms referring to extreme phenotypes in the literature, and identified common definitions and components used to describe these phenotypes. We assessed 714 definitions of HIV extreme phenotypes in 501 eligible studies published between 1 January 2000 and 15 March 2012, and identified substantial variation among these. This heterogeneity in definitions may represent important differences in biological endophenotypes and clinical progression profiles of individuals selected by these, suggesting the need for harmonized definitions. In this context, we were able to identify common components in existing definitions that may provide a framework for developing consensus definitions for these phenotypes in HIV infection.

Published
2014

18. Association of HIV and ART with cardiometabolic traits in sub-Saharan Africa: a systematic review and meta-analysis.

Author

Gurdasani, Deepti, Riha, Johanna, Ekoru, Kenneth, Asiki, Gershim, Mayanja, Billy, Levitt, Naomi, Crowther, Nigel, Nyirenda, Moffat, Njelekela, Marina, Ramaiya, Kaushik, Nyan, Ousman, Adewole, Olanisun, Anastos, Kathryn, Azzoni, Livio, Boom, W, Compostella, Caterina, Dave, Joel, Dawood, Halima, Erikstrup, Christian, Fourie, Carla, Friis, Henrik, Kruger, Annamarie, Idoko, John, Longenecker, Chris, Mbondi, Suzanne, Mukaya, Japheth, Mutimura, Eugene, Ndhlovu, Chiratidzo, Praygod, George, Pefura Yone, Eric, Pujades-Rodriguez, Mar, Range, Nyagosya, Sani, Mahmoud, Schutte, Aletta, Sliwa, Karen, Vorster, Este, Walsh, Corinna, Zinyama, Rutendo, Mashili, Fredirick, Sobngwi, Eugene, Adebamowo, Clement, Kamali, Anatoli, Seeley, Janet, Young, Elizabeth, Smeeth, Liam, Motala, Ayesha, Kaleebu, Pontiano, Sandhu, Manjinder, Tien, Phyllis, and Dillon, David

Subjects
ART, HIV, cardiometabolic disease, sub-Saharan Africa, Africa South of the Sahara, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, Body Mass Index, Diabetes Mellitus, Dyslipidemias, HIV Infections, Humans, Hypertension
Abstract

BACKGROUND: Sub-Saharan Africa (SSA) has the highest burden of HIV in the world and a rising prevalence of cardiometabolic disease; however, the interrelationship between HIV, antiretroviral therapy (ART) and cardiometabolic traits is not well described in SSA populations. METHODS: We conducted a systematic review and meta-analysis through MEDLINE and EMBASE (up to January 2012), as well as direct author contact. Eligible studies provided summary or individual-level data on one or more of the following traits in HIV+ and HIV-, or ART+ and ART- subgroups in SSA: body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TGs) and fasting blood glucose (FBG) or glycated hemoglobin (HbA1c). Information was synthesized under a random-effects model and the primary outcomes were the standardized mean differences (SMD) of the specified traits between subgroups of participants. RESULTS: Data were obtained from 49 published and 3 unpublished studies which reported on 29 755 individuals. HIV infection was associated with higher TGs [SMD, 0.26; 95% confidence interval (CI), 0.08 to 0.44] and lower HDL (SMD, -0.59; 95% CI, -0.86 to -0.31), BMI (SMD, -0.32; 95% CI, -0.45 to -0.18), SBP (SMD, -0.40; 95% CI, -0.55 to -0.25) and DBP (SMD, -0.34; 95% CI, -0.51 to -0.17). Among HIV+ individuals, ART use was associated with higher LDL (SMD, 0.43; 95% CI, 0.14 to 0.72) and HDL (SMD, 0.39; 95% CI, 0.11 to 0.66), and lower HbA1c (SMD, -0.34; 95% CI, -0.62 to -0.06). Fully adjusted estimates from analyses of individual participant data were consistent with meta-analysis of summary estimates for most traits. CONCLUSIONS: Broadly consistent with results from populations of European descent, these results suggest differences in cardiometabolic traits between HIV-infected and uninfected individuals in SSA, which might be modified by ART use. In a region with the highest burden of HIV, it will be important to clarify these findings to reliably assess the need for monitoring and managing cardiometabolic risk in HIV-infected populations in SSA.

Published
2013

19. Discovery and refinement of loci associated with lipid levels

Author

Willer, Cristen J, Schmidt, Ellen M, Sengupta, Sebanti, Peloso, Gina M, Gustafsson, Stefan, Kanoni, Stavroula, Ganna, Andrea, Chen, Jin, Buchkovich, Martin L, Mora, Samia, Beckmann, Jacques S, Bragg-Gresham, Jennifer L, Chang, Hsing-Yi, Demirkan, Ayşe, Den Hertog, Heleen M, Do, Ron, Donnelly, Louise A, Ehret, Georg B, Esko, Tõnu, Feitosa, Mary F, Ferreira, Teresa, Fischer, Krista, Fontanillas, Pierre, Fraser, Ross M, Freitag, Daniel F, Gurdasani, Deepti, Heikkilä, Kauko, Hyppönen, Elina, Isaacs, Aaron, Jackson, Anne U, Johansson, Åsa, Johnson, Toby, Kaakinen, Marika, Kettunen, Johannes, Kleber, Marcus E, Li, Xiaohui, Luan, Jian’an, Lyytikäinen, Leo-Pekka, Magnusson, Patrik KE, Mangino, Massimo, Mihailov, Evelin, Montasser, May E, Müller-Nurasyid, Martina, Nolte, Ilja M, O’Connell, Jeffrey R, Palmer, Cameron D, Perola, Markus, Petersen, Ann-Kristin, Sanna, Serena, Saxena, Richa, Service, Susan K, Shah, Sonia, Shungin, Dmitry, Sidore, Carlo, Song, Ci, Strawbridge, Rona J, Surakka, Ida, Tanaka, Toshiko, Teslovich, Tanya M, Thorleifsson, Gudmar, Van den Herik, Evita G, Voight, Benjamin F, Volcik, Kelly A, Waite, Lindsay L, Wong, Andrew, Wu, Ying, Zhang, Weihua, Absher, Devin, Asiki, Gershim, Barroso, Inês, Been, Latonya F, Bolton, Jennifer L, Bonnycastle, Lori L, Brambilla, Paolo, Burnett, Mary S, Cesana, Giancarlo, Dimitriou, Maria, Doney, Alex SF, Döring, Angela, Elliott, Paul, Epstein, Stephen E, Ingi Eyjolfsson, Gudmundur, Gigante, Bruna, Goodarzi, Mark O, Grallert, Harald, Gravito, Martha L, Groves, Christopher J, Hallmans, Göran, Hartikainen, Anna-Liisa, Hayward, Caroline, Hernandez, Dena, Hicks, Andrew A, Holm, Hilma, Hung, Yi-Jen, Illig, Thomas, Jones, Michelle R, Kaleebu, Pontiano, Kastelein, John JP, Khaw, Kay-Tee, and Kim, Eric

Subjects
Biological Sciences, Genetics, Human Genome, Cardiovascular, 2.1 Biological and endogenous factors, Asian People, Black People, Cholesterol, HDL, Cholesterol, LDL, Coronary Artery Disease, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Lipids, Triglycerides, White People, Global Lipids Genetics Consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 × 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.

Published
2013

20. Common variants associated with plasma triglycerides and risk for coronary artery disease

Author

Do, Ron, Willer, Cristen J, Schmidt, Ellen M, Sengupta, Sebanti, Gao, Chi, Peloso, Gina M, Gustafsson, Stefan, Kanoni, Stavroula, Ganna, Andrea, Chen, Jin, Buchkovich, Martin L, Mora, Samia, Beckmann, Jacques S, Bragg-Gresham, Jennifer L, Chang, Hsing-Yi, Demirkan, Ayşe, Den Hertog, Heleen M, Donnelly, Louise A, Ehret, Georg B, Esko, Tõnu, Feitosa, Mary F, Ferreira, Teresa, Fischer, Krista, Fontanillas, Pierre, Fraser, Ross M, Freitag, Daniel F, Gurdasani, Deepti, Heikkilä, Kauko, Hyppönen, Elina, Isaacs, Aaron, Jackson, Anne U, Johansson, Åsa, Johnson, Toby, Kaakinen, Marika, Kettunen, Johannes, Kleber, Marcus E, Li, Xiaohui, Luan, Jian'an, Lyytikäinen, Leo-Pekka, Magnusson, Patrik KE, Mangino, Massimo, Mihailov, Evelin, Montasser, May E, Müller-Nurasyid, Martina, Nolte, Ilja M, O'Connell, Jeffrey R, Palmer, Cameron D, Perola, Markus, Petersen, Ann-Kristin, Sanna, Serena, Saxena, Richa, Service, Susan K, Shah, Sonia, Shungin, Dmitry, Sidore, Carlo, Song, Ci, Strawbridge, Rona J, Surakka, Ida, Tanaka, Toshiko, Teslovich, Tanya M, Thorleifsson, Gudmar, Van den Herik, Evita G, Voight, Benjamin F, Volcik, Kelly A, Waite, Lindsay L, Wong, Andrew, Wu, Ying, Zhang, Weihua, Absher, Devin, Asiki, Gershim, Barroso, Inês, Been, Latonya F, Bolton, Jennifer L, Bonnycastle, Lori L, Brambilla, Paolo, Burnett, Mary S, Cesana, Giancarlo, Dimitriou, Maria, Doney, Alex SF, Döring, Angela, Elliott, Paul, Epstein, Stephen E, Eyjolfsson, Gudmundur Ingi, Gigante, Bruna, Goodarzi, Mark O, Grallert, Harald, Gravito, Martha L, Groves, Christopher J, Hallmans, Göran, Hartikainen, Anna-Liisa, Hayward, Caroline, Hernandez, Dena, Hicks, Andrew A, Holm, Hilma, Hung, Yi-Jen, Illig, Thomas, Jones, Michelle R, Kaleebu, Pontiano, Kastelein, John JP, and Khaw, Kay-Tee

Subjects
Agricultural, Veterinary and Food Sciences, Biological Sciences, Bioinformatics and Computational Biology, Genetics, Agricultural Biotechnology, Atherosclerosis, Heart Disease, Heart Disease - Coronary Heart Disease, Cardiovascular, 2.1 Biological and endogenous factors, Biological Transport, Cholesterol, HDL, Cholesterol, LDL, Coronary Artery Disease, Humans, Polymorphism, Single Nucleotide, Risk Factors, Triglycerides, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 × 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.

Published
2013

22. Evaluating the Impact of Functional Genetic Variation on HIV-1 Control

Author

McLaren, Paul J., Pulit, Sara L., Gurdasani, Deepti, Bartha, Istvan, Shea, Patrick R., Pomilla, Cristina, Gupta, Namrata, Gkrania-Klotsas, Effrossyni, Young, Elizabeth H., Bannert, Norbert, Del Amo, Julia, Gill, M John, Gilmour, Jill, Kellam, Paul, Kelleher, Anthony D., Sönnerborg, Anders, Zangerle, Robert, Post, Frank A., Fisher, Martin, Haas, David W., Walker, Bruce D., Porter, Kholoud, Goldstein, David B., Sandhu, Manjinder S., de Bakker, Paul I.W., and Fellay, Jacques

Published
2017

23. Transcriptomics and chromatin accessibility in multiple African population samples

Author

DeGorter, Marianne K, primary, Goddard, Page C, additional, Karakoc, Emre, additional, Kundu, Soumya, additional, Yan, Stephanie M, additional, Nachun, Daniel, additional, Abell, Nathan, additional, Aguirre, Matthew, additional, Carstensen, Tommy, additional, Chen, Ziwei, additional, Durrant, Matthew, additional, Dwaracherla, Vikranth R, additional, Feng, Karen, additional, Gloudemans, Michael J, additional, Hunter, Naiomi, additional, Moorthy, Mohana P S, additional, Pomilla, Cristina, additional, Rodrigues, Kameron B, additional, Smith, Courtney J, additional, Smith, Kevin S, additional, Ungar, Rachel A, additional, Balliu, Brunilda, additional, Fellay, Jacques, additional, Flicek, Paul, additional, McLaren, Paul J, additional, Henn, Brenna, additional, McCoy, Rajiv C, additional, Sugden, Lauren, additional, Kundaje, Anshul, additional, Sandhu, Manjinder S, additional, Gurdasani, Deepti, additional, and Montgomery, Stephen B, additional

Published
2023
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24. Distinct genetic architectures and environmental factors associate with host response to the γ2-herpesvirus infections

Author

Sallah, Neneh, Miley, Wendell, Labo, Nazzarena, Carstensen, Tommy, Fatumo, Segun, Gurdasani, Deepti, Pollard, Martin O., Dilthey, Alexander T., Mentzer, Alexander J., Marshall, Vickie, Cornejo Castro, Elena M., Pomilla, Cristina, Young, Elizabeth H., Asiki, Gershim, Hibberd, Martin L., Sandhu, Manjinder, Kellam, Paul, Newton, Robert, Whitby, Denise, and Barroso, Inês

Published
2020
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25. Hospital admissions linked to SARS-CoV-2 infection in children and adolescents: cohort study of 3.2 million first ascertained infections in England

Author

Wilde, Harrison, primary, Tomlinson, Christopher, additional, Mateen, Bilal A, additional, Selby, David, additional, Kanthimathinathan, Hari Krishnan, additional, Ramnarayan, Padmanabhan, additional, Du Pre, Pascale, additional, Johnson, Mae, additional, Pathan, Nazima, additional, Gonzalez-Izquierdo, Arturo, additional, Lai, Alvina G, additional, Gurdasani, Deepti, additional, Pagel, Christina, additional, Denaxas, Spiros, additional, Vollmer, Sebastian, additional, and Brown, Katherine, additional

Published
2023
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27. The transferability of lipid loci across African, Asian and European cohorts

Author

Kuchenbaecker, Karoline, Telkar, Nikita, Reiker, Theresa, Walters, Robin G., Lin, Kuang, Eriksson, Anders, Gurdasani, Deepti, Gilly, Arthur, Southam, Lorraine, Tsafantakis, Emmanouil, Karaleftheri, Maria, Seeley, Janet, Kamali, Anatoli, Asiki, Gershim, Millwood, Iona Y., Holmes, Michael, Du, Huaidong, Guo, Yu, Kumari, Meena, Dedoussis, George, Li, Liming, Chen, Zhengming, Sandhu, Manjinder S., Zeggini, Eleftheria, and Understanding Society Scientific Group

Published
2019
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28. Assessment of COVID-19 as the Underlying Cause of Death Among Children and Young People Aged 0 to 19 Years in the US

Author

Flaxman, Seth, Whittaker, Charles, Semenova, Elizaveta, Rashid, Theo, Parks, Robbie M., Blenkinsop, Alexandra, Unwin, H. Juliette T., Mishra, Swapnil, Bhatt, Samir, Gurdasani, Deepti, Ratmann, Oliver, Flaxman, Seth, Whittaker, Charles, Semenova, Elizaveta, Rashid, Theo, Parks, Robbie M., Blenkinsop, Alexandra, Unwin, H. Juliette T., Mishra, Swapnil, Bhatt, Samir, Gurdasani, Deepti, and Ratmann, Oliver

Abstract

Importance COVID-19 was the underlying cause of death for more than 940 000 individuals in the US, including at least 1289 children and young people (CYP) aged 0 to 19 years, with at least 821 CYP deaths occurring in the 1-year period from August 1, 2021, to July 31, 2022. Because deaths among US CYP are rare, the mortality burden of COVID-19 in CYP is best understood in the context of all other causes of CYP death. Objective To determine whether COVID-19 is a leading (top 10) cause of death in CYP in the US. Design, Setting, and Participants This national population-level cross-sectional epidemiological analysis for the years 2019 to 2022 used data from the US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (WONDER) database on underlying cause of death in the US to identify the ranking of COVID-19 relative to other causes of death among individuals aged 0 to 19 years. COVID-19 deaths were considered in 12-month periods between April 1, 2020, and August 31, 2022, compared with deaths from leading non–COVID-19 causes in 2019, 2020, and 2021. Main Outcomes and Measures Cause of death rankings by total number of deaths, crude rates per 100 000 population, and percentage of all causes of death, using the National Center for Health Statistics 113 Selected Causes of Death, for ages 0 to 19 and by age groupings (<1 year, 1-4 years, 5-9 years, 10-14 years, 15-19 years). Results There were 821 COVID-19 deaths among individuals aged 0 to 19 years during the study period, resulting in a crude death rate of 1.0 per 100 000 population overall; 4.3 per 100 000 for those younger than 1 year; 0.6 per 100 000 for those aged 1 to 4 years; 0.4 per 100 000 for those aged 5 to 9 years; 0.5 per 100 000 for those aged 10 to 14 years; and 1.8 per 100 000 for those aged 15 to 19 years. COVID-19 mortality in the time period of August 1, 2021, to July 31, 2022, was among the 10 leading causes of death in CY, Importance: COVID-19 was the underlying cause of death for more than 940 000 individuals in the US, including at least 1289 children and young people (CYP) aged 0 to 19 years, with at least 821 CYP deaths occurring in the 1-year period from August 1, 2021, to July 31, 2022. Because deaths among US CYP are rare, the mortality burden of COVID-19 in CYP is best understood in the context of all other causes of CYP death. Objective: To determine whether COVID-19 is a leading (top 10) cause of death in CYP in the US. Design, Setting, and Participants: This national population-level cross-sectional epidemiological analysis for the years 2019 to 2022 used data from the US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (WONDER) database on underlying cause of death in the US to identify the ranking of COVID-19 relative to other causes of death among individuals aged 0 to 19 years. COVID-19 deaths were considered in 12-month periods between April 1, 2020, and August 31, 2022, compared with deaths from leading non-COVID-19 causes in 2019, 2020, and 2021. Main Outcomes and Measures: Cause of death rankings by total number of deaths, crude rates per 100 000 population, and percentage of all causes of death, using the National Center for Health Statistics 113 Selected Causes of Death, for ages 0 to 19 and by age groupings (<1 year, 1-4 years, 5-9 years, 10-14 years, 15-19 years). Results: There were 821 COVID-19 deaths among individuals aged 0 to 19 years during the study period, resulting in a crude death rate of 1.0 per 100 000 population overall; 4.3 per 100 000 for those younger than 1 year; 0.6 per 100 000 for those aged 1 to 4 years; 0.4 per 100 000 for those aged 5 to 9 years; 0.5 per 100 000 for those aged 10 to 14 years; and 1.8 per 100 000 for those aged 15 to 19 years. COVID-19 mortality in the time period of August 1, 2021, to July 31, 2022, was among the 10 leading causes of death in CYP aged 0 to 19 years in the

Published
2023

30. Polymorphisms of large effect explain the majority of the host genetic contribution to variation of HIV-1 virus load

Author

McLaren, Paul J., Coulonges, Cedric, Bartha, István, Lenz, Tobias L., Deutsch, Aaron J., Bashirova, Arman, Buchbinder, Susan, Carrington, Mary N., Cossarizza, Andrea, Dalmau, Judith, De Luca, Andrea, Goedert, James J., Gurdasani, Deepti, Haas, David W., Herbeck, Joshua T., Johnson, Eric O., Kirk, Gregory D., Lambotte, Olivier, Luo, Ma, Mallal, Simon, van Manen, Daniëlle, Martinez-Picado, Javier, Meyer, Laurence, Miro, José M., Mullins, James I., Obel, Niels, Poli, Guido, Sandhu, Manjinder S., Schuitemaker, Hanneke, Shea, Patrick R., Theodorou, Ioannis, Walker, Bruce D., Weintrob, Amy C., Winkler, Cheryl A., Wolinsky, Steven M., Raychaudhuri, Soumya, Goldstein, David B., Telenti, Amalio, de Bakker, Paul I. W., Zagury, Jean-François, and Fellay, Jacques

Published
2015

31. Assessment of COVID-19 as the Underlying Cause of Death Among Children and Young People Aged 0 to 19 Years in the US

Author

Flaxman, Seth, primary, Whittaker, Charles, additional, Semenova, Elizaveta, additional, Rashid, Theo, additional, Parks, Robbie M., additional, Blenkinsop, Alexandra, additional, Unwin, H. Juliette T., additional, Mishra, Swapnil, additional, Bhatt, Samir, additional, Gurdasani, Deepti, additional, and Ratmann, Oliver, additional

Published
2023
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32. High-resolution African HLA resource uncovers HLA-DRB1expression effects underlying vaccine response

Author

Mentzer, Alexander J., Dilthey, Alexander T., Pollard, Martin, Gurdasani, Deepti, Karakoc, Emre, Carstensen, Tommy, Muhwezi, Allan, Cutland, Clare, Diarra, Amidou, da Silva Antunes, Ricardo, Paul, Sinu, Smits, Gaby, Wareing, Susan, Kim, HwaRan, Pomilla, Cristina, Chong, Amanda Y., Brandt, Debora Y. C., Nielsen, Rasmus, Neaves, Samuel, Timpson, Nicolas, Crinklaw, Austin, Lindestam Arlehamn, Cecilia S., Rautanen, Anna, Kizito, Dennison, Parks, Tom, Auckland, Kathryn, Elliott, Kate E., Mills, Tara, Ewer, Katie, Edwards, Nick, Fatumo, Segun, Webb, Emily, Peacock, Sarah, Jeffery, Katie, van der Klis, Fiona R. M., Kaleebu, Pontiano, Vijayanand, Pandurangan, Peters, Bjorn, Sette, Alessandro, Cereb, Nezih, Sirima, Sodiomon, Madhi, Shabir A., Elliott, Alison M., McVean, Gil, Hill, Adrian V. S., and Sandhu, Manjinder S.

Abstract

How human genetic variation contributes to vaccine effectiveness in infants is unclear, and data are limited on these relationships in populations with African ancestries. We undertook genetic analyses of vaccine antibody responses in infants from Uganda (n= 1391), Burkina Faso (n= 353) and South Africa (n= 755), identifying associations between human leukocyte antigen (HLA) and antibody response for five of eight tested antigens spanning pertussis, diphtheria and hepatitis B vaccines. In addition, through HLA typing 1,702 individuals from 11 populations of African ancestry derived predominantly from the 1000 Genomes Project, we constructed an imputation resource, fine-mapping class II HLA-DR and DQ associations explaining up to 10% of antibody response variance in our infant cohorts. We observed differences in the genetic architecture of pertussis antibody response between the cohorts with African ancestries and an independent cohort with European ancestry, but found no in silico evidence of differences in HLA peptide binding affinity or breadth. Using immune cell expression quantitative trait loci datasets derived from African-ancestry samples from the 1000 Genomes Project, we found evidence of differential HLA-DRB1expression correlating with inferred protection from pertussis following vaccination. This work suggests that HLA-DRB1expression may play a role in vaccine response and should be considered alongside peptide selection to improve vaccine design.

Published
2024
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33. High-resolution African HLA resource uncoversHLA-DRB1expression effects underlying vaccine response

Author

Mentzer, Alexander J., primary, Dilthey, Alexander T., additional, Pollard, Martin, additional, Gurdasani, Deepti, additional, Karakoc, Emre, additional, Carstensen, Tommy, additional, Muhwezi, Allan, additional, Cutland, Clare, additional, Diarra, Amidou, additional, Antunes, Ricardo da Silva, additional, Paul, Sinu, additional, Smits, Gaby, additional, Wareing, Susan, additional, Kim, HwaRan, additional, Pomilla, Cristina, additional, Chong, Amanda Y., additional, Brandt, Debora Y.C., additional, Nielsen, Rasmus, additional, Neaves, Samuel, additional, Timpson, Nicolas, additional, Crinklaw, Austin, additional, Lindestam Arlehamn, Cecilia S., additional, Rautanen, Anna, additional, Kizito, Dennison, additional, Parks, Tom, additional, Auckland, Kathryn, additional, Elliott, Kate E., additional, Mills, Tara, additional, Ewer, Katie, additional, Edwards, Nick, additional, Fatumo, Segun, additional, Peacock, Sarah, additional, Jeffery, Katie, additional, van der Klis, Fiona R.M., additional, Kaleebu, Pontiano, additional, Vijayanand, Pandurangan, additional, Peters, Bjorn, additional, Sette, Alessandro, additional, Cereb, Nezih, additional, Sirima, Sodiomon, additional, Madhi, Shabir A., additional, Elliott, Alison M., additional, McVean, Gil, additional, Hill, Adrian V.S., additional, and Sandhu, Manjinder S., additional

Published
2022
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35. COVID-19 and children

Author

Pierce, Carl A., primary, Herold, Kevan C., additional, Herold, Betsy C., additional, Chou, Janet, additional, Randolph, Adrienne, additional, Kane, Binita, additional, McFarland, Sammie, additional, Gurdasani, Deepti, additional, Pagel, Christina, additional, Hotez, Peter, additional, Cobey, Sarah, additional, and Hensley, Scott E., additional

Published
2022
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37. Covid-19 in the UK: policy on children and schools

Author

Gurdasani, Deepti, primary, Pagel, Christina, additional, McKee, Martin, additional, Michie, Susan, additional, Greenhalgh, Trish, additional, Yates, Christopher, additional, Scally, Gabriel, additional, and Ziauddeen, Hisham, additional

Published
2022
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38. COVID-19 trajectories among 57 million adults in England: a cohort study using electronic health records

Author

Thygesen, Johan H, primary, Tomlinson, Christopher, additional, Hollings, Sam, additional, Mizani, Mehrdad A, additional, Handy, Alex, additional, Akbari, Ashley, additional, Banerjee, Amitava, additional, Cooper, Jennifer, additional, Lai, Alvina G, additional, Li, Kezhi, additional, Mateen, Bilal A, additional, Sattar, Naveed, additional, Sofat, Reecha, additional, Torralbo, Ana, additional, Wu, Honghan, additional, Wood, Angela, additional, Sterne, Jonathan A C, additional, Pagel, Christina, additional, Whiteley, William N, additional, Sudlow, Cathie, additional, Hemingway, Harry, additional, Denaxas, Spiros, additional, Abbasizanjani, Hoda, additional, Ahmed, Nida, additional, Ahmed, Badar, additional, Akinoso-Imran, Abdul Qadr, additional, Allara, Elias, additional, Allery, Freya, additional, Angelantonio, Emanuele Di, additional, Ashworth, Mark, additional, Ayyar-Gupta, Vandana, additional, Babu-Narayan, Sonya, additional, Bacon, Seb, additional, Ball, Steve, additional, Banerjee, Ami, additional, Barber, Mark, additional, Barrett, Jessica, additional, Bennie, Marion, additional, Berry, Colin, additional, Beveridge, Jennifer, additional, Birney, Ewan, additional, Bojanić, Lana, additional, Bolton, Thomas, additional, Bone, Anna, additional, Boyle, Jon, additional, Braithwaite, Tasanee, additional, Bray, Ben, additional, Briffa, Norman, additional, Brind, David, additional, Brown, Katherine, additional, Buch, Maya, additional, Canoy, Dexter, additional, Caputo, Massimo, additional, Carragher, Raymond, additional, Carson, Alan, additional, Cezard, Genevieve, additional, Chang, Jen-Yu Amy, additional, Cheema, Kate, additional, Chin, Richard, additional, Chudasama, Yogini, additional, Copland, Emma, additional, Crallan, Rebecca, additional, Cripps, Rachel, additional, Cromwell, David, additional, Curcin, Vasa, additional, Curry, Gwenetta, additional, Dale, Caroline, additional, Danesh, John, additional, Das-Munshi, Jayati, additional, Dashtban, Ashkan, additional, Davies, Alun, additional, Davies, Joanna, additional, Davies, Gareth, additional, Davies, Neil, additional, Day, Joshua, additional, Delmestri, Antonella, additional, Denholm, Rachel, additional, Dennis, John, additional, Denniston, Alastair, additional, Deo, Salil, additional, Dhillon, Baljean, additional, Docherty, Annemarie, additional, Dong, Tim, additional, Douiri, Abdel, additional, Downs, Johnny, additional, Dregan, Alexandru, additional, Ellins, Elizabeth A, additional, Elwenspoek, Martha, additional, Falck, Fabian, additional, Falter, Florian, additional, Fan, Yat Yi, additional, Firth, Joseph, additional, Fraser, Lorna, additional, Friebel, Rocco, additional, Gavrieli, Amir, additional, Gerstung, Moritz, additional, Gilbert, Ruth, additional, Gillies, Clare, additional, Glickman, Myer, additional, Goldacre, Ben, additional, Goldacre, Raph, additional, Greaves, Felix, additional, Green, Mark, additional, Grieco, Luca, additional, Griffiths, Rowena, additional, Gurdasani, Deepti, additional, Halcox, Julian, additional, Hall, Nick, additional, Hama, Tuankasfee, additional, Hansell, Anna, additional, Hardelid, Pia, additional, Hardy, Flavien, additional, Harris, Daniel, additional, Harrison, Camille, additional, Harron, Katie, additional, Hassaine, Abdelaali, additional, Hassan, Lamiece, additional, Healey, Russell, additional, Henderson, Angela, additional, Herz, Naomi, additional, Heyl, Johannes, additional, Hidajat, Mira, additional, Higginson, Irene, additional, Hinchliffe, Rosie, additional, Hippisley-Cox, Julia, additional, Ho, Frederick, additional, Hocaoglu, Mevhibe, additional, Horne, Elsie, additional, Hughes, David, additional, Humberstone, Ben, additional, Inouye, Mike, additional, Ip, Samantha, additional, Islam, Nazrul, additional, Jackson, Caroline, additional, Jenkins, David, additional, Jiang, Xiyun, additional, Johnson, Shane, additional, Kadam, Umesh, additional, Kallis, Costas, additional, Karim, Zainab, additional, Kasan, Jake, additional, Katsoulis, Michalis, additional, Kavanagh, Kim, additional, Kee, Frank, additional, Keene, Spencer, additional, Kent, Seamus, additional, Khalid, Sara, additional, Khawaja, Anthony, additional, Khunti, Kamlesh, additional, Killick, Richard, additional, Kinnear, Deborah, additional, Knight, Rochelle, additional, Kolamunnage-Dona, Ruwanthi, additional, Kontopantelis, Evan, additional, Kurdi, Amanj, additional, Lacey, Ben, additional, Lai, Alvina, additional, Lambarth, Andrew, additional, Larzjan, Milad Nazarzadeh, additional, Lawler, Deborah, additional, Lawrence, Thomas, additional, Lawson, Claire, additional, Li, Qiuju, additional, Li, Ken, additional, Llinares, Miguel Bernabeu, additional, Lorgelly, Paula, additional, Lowe, Deborah, additional, Lyons, Jane, additional, Lyons, Ronan, additional, Machado, Pedro, additional, Macleod, Mary Joan, additional, Macleod, John, additional, Malgapo, Evaleen, additional, Mamas, Mamas, additional, Mamouei, Mohammad, additional, Manohar, Sinduja, additional, Mapeta, Rutendo, additional, Martelli, Javiera Leniz, additional, Martos, David Moreno, additional, Mateen, Bilal, additional, McCarthy, Aoife, additional, Melville, Craig, additional, Milton, Rebecca, additional, Mizani, Mehrdad, additional, Moncusi, Marta Pineda, additional, Morales, Daniel, additional, Mordi, Ify, additional, Morrice, Lynn, additional, Morris, Carole, additional, Morris, Eva, additional, Mu, Yi, additional, Mueller, Tanja, additional, Murdock, Lars, additional, Nafilyan, Vahé, additional, Nicholson, George, additional, Nikiphorou, Elena, additional, Nolan, John, additional, Norris, Tom, additional, Norris, Ruth, additional, North, Laura, additional, North, Teri-Louise, additional, O'Connell, Dan, additional, Oliver, Dominic, additional, Oluyase, Adejoke, additional, Olvera-Barrios, Abraham, additional, Omigie, Efosa, additional, Onida, Sarah, additional, Padmanabhan, Sandosh, additional, Palmer, Tom, additional, Pasea, Laura, additional, Patel, Riyaz, additional, Payne, Rupert, additional, Pell, Jill, additional, Petitjean, Carmen, additional, Pherwani, Arun, additional, Pickrell, Owen, additional, Pierotti, Livia, additional, Pirmohamed, Munir, additional, Priedon, Rouven, additional, Prieto-Alhambra, Dani, additional, Proudfoot, Alastair, additional, Quinn, Terry, additional, Quint, Jennifer, additional, Raffetti, Elena, additional, Rahimi, Kazem, additional, Rao, Shishir, additional, Razieh, Cameron, additional, Roberts, Brian, additional, Rogers, Caroline, additional, Rossdale, Jennifer, additional, Salim, Safa, additional, Samani, Nilesh, additional, Schnier, Christian, additional, Schwartz, Roy, additional, Selby, David, additional, Seminog, Olena, additional, Shabnam, Sharmin, additional, Shah, Ajay, additional, Shelton, Jon, additional, Sheppard, James, additional, Sinha, Shubhra, additional, Skrypak, Mirek, additional, Slapkova, Martina, additional, Sleeman, Katherine, additional, Smith, Craig, additional, Sosenko, Filip, additional, Sperrin, Matthew, additional, Steeg, Sarah, additional, Sterne, Jonathan, additional, Stoica, Serban, additional, Sudell, Maria, additional, Sun, Luanluan, additional, Suseeladevi, Arun Karthikeyan, additional, Sweeting, Michael, additional, Sydes, Matt, additional, Takhar, Rohan, additional, Tang, Howard, additional, Thygesen, Johan, additional, Tilston, George, additional, Tochel, Claire, additional, Toit, Clea du, additional, Toms, Renin, additional, Torabi, Fatemeh, additional, Townson, Julia, additional, Tufail, Adnan, additional, Tungamirai, Tapiwa, additional, Varma, Susheel, additional, Vollmer, Sebastian, additional, Walker, Venexia, additional, Wang, Tianxiao, additional, Wang, Huan, additional, Warwick, Alasdair, additional, Watkinson, Ruth, additional, Watson, Harry, additional, Whiteley, William, additional, Whittaker, Hannah, additional, Wilde, Harry, additional, Wilkinson, Tim, additional, Williams, Gareth, additional, Williams, Michelle, additional, Williams, Richard, additional, Withnell, Eloise, additional, Wolfe, Charles, additional, Wright, Lucy, additional, Wu, Jinge, additional, Wu, Jianhua, additional, Yates, Tom, additional, Zaccardi, Francesco, additional, Zhang, Haoting, additional, Zhang, Huayu, additional, and Zuccolo, Luisa, additional

Published
2022
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42. The African Genome Variation Project shapes medical genetics in Africa

Author

Gurdasani, Deepti, Carstensen, Tommy, Tekola-Ayele, Fasil, Pagani, Luca, Tachmazidou, Ioanna, Hatzikotoulas, Konstantinos, Karthikeyan, Savita, Iles, Louise, Pollard, Martin O., Choudhury, Ananyo, Ritchie, Graham R.S., Xue, Yali, Asimit, Jennifer, Nsubuga, Rebecca N., Young, Elizabeth H., and Pomilla, Cristina

Subjects
Research, Medical genetics -- Research, Genetic research, Genetic variation -- Research
Abstract

Author(s): Deepti Gurdasani [sup.1] [sup.2] , Tommy Carstensen [sup.1] [sup.2] , Fasil Tekola-Ayele [sup.3] , Luca Pagani [sup.1] [sup.4] , Ioanna Tachmazidou [sup.1] , Konstantinos Hatzikotoulas [sup.1] , Savita Karthikeyan [...], Given the importance of Africa to studies of human origins and disease susceptibility, detailed characterization of African genetic diversity is needed. The African Genome Variation Project provides a resource with which to design, implement and interpret genomic studies in sub-Saharan Africa and worldwide. The African Genome Variation Project represents dense genotypes from 1,481 individuals and whole-genome sequences from 320 individuals across sub-Saharan Africa. Using this resource, we find novel evidence of complex, regionally distinct hunter-gatherer and Eurasian admixture across sub-Saharan Africa. We identify new loci under selection, including loci related to malaria susceptibility and hypertension. We show that modern imputation panels (sets of reference genotypes from which unobserved or missing genotypes in study sets can be inferred) can identify association signals at highly differentiated loci across populations in sub-Saharan Africa. Using whole-genome sequencing, we demonstrate further improvements in imputation accuracy, strengthening the case for large-scale sequencing efforts of diverse African haplotypes. Finally, we present an efficient genotype array design capturing common genetic variation in Africa. The African Genome Variation Project contains the whole-genome sequences of 320 individuals and dense genotypes on 1,481 individuals from sub-Saharan Africa; it enables the design and interpretation of genomic studies, with implications for finding disease loci and clues to human origins. Genetic variation in sub-Saharan Africa The African Genome Variation Project (AGVP) is collecting data on the structure of African genomes to provide a central resource for genetic disease studies in Africa. It currently represents dense genotypes from 1,481 individuals and whole-genome sequences from 320 individuals across sub-Saharan Africa. Using these data, Manjinder Sandhu and colleagues identify new loci under selection, including those associated with malaria and hypertension. They show that modern imputation panels can identify association signals at highly differentiated loci across population groups. They demonstrate the utility of whole-genome sequences in further improving the imputation accuracy. In addition, they describe the first efficient genotype array design capturing common genetic variation in Africa.

Published
2015
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43. Long COVID in children

Author

Gurdasani, Deepti, primary, Akrami, Athena, additional, Bradley, Valerie C, additional, Costello, Anthony, additional, Greenhalgh, Trisha, additional, Flaxman, Seth, additional, McKee, Martin, additional, Michie, Susan, additional, Pagel, Christina, additional, Rasmussen, Sarah, additional, Scally, Gabriel, additional, Yates, Christian, additional, and Ziauddeen, Hisham, additional

Published
2022
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44. Africa-specific human genetic variation near CHD1Lassociates with HIV-1 load

Author

McLaren, Paul J., Porreca, Immacolata, Iaconis, Gennaro, Mok, Hoi Ping, Mukhopadhyay, Subhankar, Karakoc, Emre, Cristinelli, Sara, Pomilla, Cristina, Bartha, István, Thorball, Christian W., Tough, Riley H., Angelino, Paolo, Kiar, Cher S., Carstensen, Tommy, Fatumo, Segun, Porter, Tarryn, Jarvis, Isobel, Skarnes, William C., Bassett, Andrew, DeGorter, Marianne K., Sathya Moorthy, Mohana Prasad, Tuff, Jeffrey F., Kim, Eun-Young, Walter, Miriam, Simons, Lacy M., Bashirova, Arman, Buchbinder, Susan, Carrington, Mary, Cossarizza, Andrea, De Luca, Andrea, Goedert, James J., Goldstein, David B., Haas, David W., Herbeck, Joshua T., Johnson, Eric O., Kaleebu, Pontiano, Kilembe, William, Kirk, Gregory D., Kootstra, Neeltje A., Kral, Alex H., Lambotte, Olivier, Luo, Ma, Mallal, Simon, Martinez-Picado, Javier, Meyer, Laurence, Miro, José M., Moodley, Pravi, Motala, Ayesha A., Mullins, James I., Nam, Kireem, Obel, Niels, Pirie, Fraser, Plummer, Francis A., Poli, Guido, Price, Matthew A., Rauch, Andri, Theodorou, Ioannis, Trkola, Alexandra, Walker, Bruce D., Winkler, Cheryl A., Zagury, Jean-François, Montgomery, Stephen B., Ciuffi, Angela, Hultquist, Judd F., Wolinsky, Steven M., Dougan, Gordon, Lever, Andrew M. L., Gurdasani, Deepti, Groom, Harriet, Sandhu, Manjinder S., and Fellay, Jacques

Abstract

HIV-1 remains a global health crisis1, highlighting the need to identify new targets for therapies. Here, given the disproportionate HIV-1 burden and marked human genome diversity in Africa2, we assessed the genetic determinants of control of set-point viral load in 3,879 people of African ancestries living with HIV-1 participating in the international collaboration for the genomics of HIV3. We identify a previously undescribed association signal on chromosome 1 where the peak variant associates with an approximately 0.3 log10-transformed copies per ml lower set-point viral load per minor allele copy and is specific to populations of African descent. The top associated variant is intergenic and lies between a long intergenic non-coding RNA (LINC00624) and the coding gene CHD1L, which encodes a helicase that is involved in DNA repair4. Infection assays in iPS cell-derived macrophages and other immortalized cell lines showed increased HIV-1 replication in CHD1L-knockdown and CHD1L-knockout cells. We provide evidence from population genetic studies that Africa-specific genetic variation near CHD1Lassociates with HIV replication in vivo. Although experimental studies suggest that CHD1L is able to limit HIV infection in some cell types in vitro, further investigation is required to understand the mechanisms underlying our observations, including any potential indirect effects of CHD1L on HIV spread in vivo that our cell-based assays cannot recapitulate.

Published
2023
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47. Vaccinating adolescents against SARS-CoV-2 in England: a risk–benefit analysis

Author

Gurdasani, Deepti, primary, Bhatt, Samir, additional, Costello, Anthony, additional, Denaxas, Spiros, additional, Flaxman, Seth, additional, Greenhalgh, Trisha, additional, Griffin, Stephen, additional, Hyde, Zoë, additional, Katzourakis, Aris, additional, McKee, Martin, additional, Michie, Susan, additional, Ratmann, Oliver, additional, Reicher, Stephen, additional, Scally, Gabriel, additional, Tomlinson, Christopher, additional, Yates, Christian, additional, Ziauddeen, Hisham, additional, and Pagel, Christina, additional

Published
2021
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50. The World Health Network: a global citizens' initiative

Author

Bar-Yam, Yaneer, primary, Gurdasani, Deepti, additional, Baker, Michael G, additional, Scally, Gabriel, additional, George, Simone, additional, Kvalsvig, Amanda, additional, Fhaoláin, Sinéad Ní, additional, Chiou, Shu-Ti, additional, Drury, John, additional, Duckett, Stephen, additional, Ding, Eric L, additional, Gershenson, Carlos, additional, Gibson, Christine, additional, Greenhalgh, Trisha, additional, Hamdy, Adam, additional, Hyde, Zoë, additional, James, Tiffany, additional, Jimenez, Jose L, additional, McKee, Martin, additional, Michie, Susan, additional, Pagel, Christina, additional, Philippe, Cecile, additional, Prather, Kim, additional, Raina, Sunil K, additional, Ricciardi, Walter, additional, Rubin, Meir, additional, Ryan, Tomás, additional, Schneider, Matthias F, additional, Staines, Anthony, additional, West, Robert, additional, and Ziauddeen, Hisham, additional

Published
2021
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