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1. Genome-wide host-pathogen analyses reveal genetic interaction points in tuberculosis disease

Author

Phelan, Jody, Gomez-Gonzalez, Paula Josefina, Andreu, Nuria, Omae, Yosuke, Toyo-Oka, Licht, Yanai, Hideki, Miyahara, Reiko, Nedsuwan, Supalert, de Sessions, Paola Florez, Campino, Susana, Sallah, Neneh, Parkhill, Julian, Smittipat, Nat, Palittapongarnpim, Prasit, Mushiroda, Taisei, Kubo, Michiaki, Tokunaga, Katsushi, Mahasirimongkol, Surakameth, Hibberd, Martin L., and Clark, Taane G.

Published
2023
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2. Identification of novel locus associated with coronary artery aneurysms and validation of loci for susceptibility to Kawasaki disease.

Author

Hoggart, Clive, Shimizu, Chisato, Galassini, Rachel, Wright, Victoria J, Shailes, Hannah, Bellos, Evan, Herberg, Jethro A, Pollard, Andrew J, O'Connor, Daniel, Choi, Shing Wan, Seaby, Eleanor G, Menikou, Stephanie, Hibberd, Martin, Sallah, Neneh, Burgner, David, Brogan, Paul, Patel, Harsita, Kim, Jihoon, Tremoulet, Adriana H, Salo, Eeva, van Stijn, Diana, Kuijpers, Taco, Burns, Jane C, Levin, Michael, International Kawasaki Disease Genetics Consortium, UK Kawasaki Disease Genetics Consortium, and EUCLIDS Consortium

Subjects
International Kawasaki Disease Genetics Consortium, UK Kawasaki Disease Genetics Consortium, EUCLIDS Consortium, Humans, Coronary Aneurysm, Mucocutaneous Lymph Node Syndrome, Phosphotransferases (Alcohol Group Acceptor), Proteins, Receptors, IgG, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Caspase 3, Rare Diseases, Human Genome, Prevention, Genetics, Autoimmune Disease, Aetiology, 2.1 Biological and endogenous factors, Clinical Sciences, Genetics & Heredity
Abstract

Kawasaki disease (KD) is a paediatric vasculitis associated with coronary artery aneurysms (CAA). Genetic variants influencing susceptibility to KD have been previously identified, but no risk alleles have been validated that influence CAA formation. We conducted a genome-wide association study (GWAS) for CAA in KD patients of European descent with 200 cases and 276 controls. A second GWAS for susceptibility pooled KD cases with healthy paediatric controls from vaccine trials in the UK (n = 1609). Logistic regression mixed models were used for both GWASs. The susceptibility GWAS was meta-analysed with 400 KD cases and 6101 controls from a previous European GWAS, these results were further meta-analysed with Japanese GWASs at two putative loci. The CAA GWAS identified an intergenic region of chromosome 20q13 with multiple SNVs showing genome-wide significance. The risk allele of the most associated SNV (rs6017006) was present in 13% of cases and 4% of controls; in East Asian 1000 Genomes data, the allele was absent or rare. Susceptibility GWAS with meta-analysis with previously published European data identified two previously associated loci (ITPKC and FCGR2A). Further meta-analysis with Japanese GWAS summary data from the CASP3 and FAM167A genomic regions validated these loci in Europeans showing consistent effects of the top SNVs in both populations. We identified a novel locus for CAA in KD patients of European descent. The results suggest that different genes determine susceptibility to KD and development of CAA and future work should focus on the function of the intergenic region on chromosome 20q13.

Published
2021

5. Integrating polygenic risk scores in the prediction of type 2 diabetes risk and subtypes in British Pakistanis and Bangladeshis: A population-based cohort study

Author

Hodgson, Sam, Huang, Qin Qin, Sallah, Neneh, Griffiths, Chris J., Newman, William G., Trembath, Richard C., Wright, John, Lumbers, R. Thomas, Kuchenbaecker, Karoline, van Heel, David A., Mathur, Rohini, Martin, Hilary C., and Finer, Sarah

Subjects
Bangladeshis -- Health aspects -- Genetic aspects, Pakistanis -- Health aspects -- Genetic aspects, Type 2 diabetes -- Risk factors -- Genetic aspects, Biological sciences
Abstract

Background Type 2 diabetes (T2D) is highly prevalent in British South Asians, yet they are underrepresented in research. Genes & Health (G&H) is a large, population study of British Pakistanis and Bangladeshis (BPB) comprising genomic and routine health data. We assessed the extent to which genetic risk for T2D is shared between BPB and European populations (EUR). We then investigated whether the integration of a polygenic risk score (PRS) for T2D with an existing risk tool (QDiabetes) could improve prediction of incident disease and the characterisation of disease subtypes. Methods and findings In this observational cohort study, we assessed whether common genetic loci associated with T2D in EUR individuals were replicated in 22,490 BPB individuals in G&H. We replicated fewer loci in G&H (n = 76/338, 22%) than would be expected given power if all EUR-ascertained loci were transferable (n = 101, 30%; p = 0.001). Of the 27 transferable loci that were powered to interrogate this, only 9 showed evidence of shared causal variants. We constructed a T2D PRS and combined it with a clinical risk instrument (QDiabetes) in a novel, integrated risk tool (IRT) to assess risk of incident diabetes. To assess model performance, we compared categorical net reclassification index (NRI) versus QDiabetes alone. In 13,648 patients free from T2D followed up for 10 years, NRI was 3.2% for IRT versus QDiabetes (95% confidence interval (CI): 2.0% to 4.4%). IRT performed best in reclassification of individuals aged less than 40 years deemed low risk by QDiabetes alone (NRI 5.6%, 95% CI 3.6% to 7.6%), who tended to be free from comorbidities and slim. After adjustment for QDiabetes score, PRS was independently associated with progression to T2D after gestational diabetes (hazard ratio (HR) per SD of PRS 1.23, 95% CI 1.05 to 1.42, p = 0.028). Using cluster analysis of clinical features at diabetes diagnosis, we replicated previously reported disease subgroups, including Mild Age-Related, Mild Obesity-related, and Insulin-Resistant Diabetes, and showed that PRS distribution differs between subgroups (p = 0.002). Integrating PRS in this cluster analysis revealed a Probable Severe Insulin Deficient Diabetes (pSIDD) subgroup, despite the absence of clinical measures of insulin secretion or resistance. We also observed differences in rates of progression to micro- and macrovascular complications between subgroups after adjustment for confounders. Study limitations include the absence of an external replication cohort and the potential biases arising from missing or incorrect routine health data. Conclusions Our analysis of the transferability of T2D loci between EUR and BPB indicates the need for larger, multiancestry studies to better characterise the genetic contribution to disease and its varied aetiology. We show that a T2D PRS optimised for this high-risk BPB population has potential clinical application in BPB, improving the identification of T2D risk (especially in the young) on top of an established clinical risk algorithm and aiding identification of subgroups at diagnosis, which may help future efforts to stratify care and treatment of the disease., Author(s): Sam Hodgson 1, Qin Qin Huang 2, Neneh Sallah 3,4, Genes & Health Research Team 5,6, Chris J. Griffiths 5, William G. Newman 7,8, Richard C. Trembath 9, John [...]

Published
2022
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6. 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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7. Identification of novel locus associated with coronary artery aneurysms and validation of loci for susceptibility to Kawasaki disease

Author

Hoggart, Clive, Shimizu, Chisato, Galassini, Rachel, Wright, Victoria J., Shailes, Hannah, Bellos, Evan, Herberg, Jethro A., Pollard, Andrew J., O’Connor, Daniel, Choi, Shing Wan, Seaby, Eleanor G., Menikou, Stephanie, Hibberd, Martin, Sallah, Neneh, Burgner, David, Brogan, Paul, Patel, Harsita, Kim, Jihoon, Tremoulet, Adriana H., Salo, Eeva, van Stijn, Diana, Kuijpers, Taco, Burns, Jane C., and Levin, Michael

Abstract

Kawasaki disease (KD) is a paediatric vasculitis associated with coronary artery aneurysms (CAA). Genetic variants influencing susceptibility to KD have been previously identified, but no risk alleles have been validated that influence CAA formation. We conducted a genome-wide association study (GWAS) for CAA in KD patients of European descent with 200 cases and 276 controls. A second GWAS for susceptibility pooled KD cases with healthy paediatric controls from vaccine trials in the UK (n= 1609). Logistic regression mixed models were used for both GWASs. The susceptibility GWAS was meta-analysed with 400 KD cases and 6101 controls from a previous European GWAS, these results were further meta-analysed with Japanese GWASs at two putative loci. The CAA GWAS identified an intergenic region of chromosome 20q13 with multiple SNVs showing genome-wide significance. The risk allele of the most associated SNV (rs6017006) was present in 13% of cases and 4% of controls; in East Asian 1000 Genomes data, the allele was absent or rare. Susceptibility GWAS with meta-analysis with previously published European data identified two previously associated loci (ITPKCand FCGR2A). Further meta-analysis with Japanese GWAS summary data from the CASP3and FAM167Agenomic regions validated these loci in Europeans showing consistent effects of the top SNVs in both populations. We identified a novel locus for CAA in KD patients of European descent. The results suggest that different genes determine susceptibility to KD and development of CAA and future work should focus on the function of the intergenic region on chromosome 20q13.

Published
2024
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8. Systematic analysis of Kaposi's sarcoma (KS)‐associated herpesvirus genomes from a KS case‐control study in Cameroon: Evidence of dual infections but no association between viral sequence variation and KS risk

Author

Marshall, Vickie A., primary, Fisher, Nicholas C., additional, Goodman, Charles A., additional, Cornejo Castro, Elena M., additional, Liu, Isabella, additional, Khanal, Sirish, additional, Holdridge, Benjamin M., additional, Thorpe, Abigail L., additional, Labo, Nazzarena, additional, Stolka, Kristen B., additional, Hemingway‐Foday, Jennifer J., additional, Abassora, Mahamat, additional, N'Dom, Paul, additional, Smith, Jennifer S., additional, Sallah, Neneh, additional, Palser, Anne L., additional, Kellam, Paul, additional, Keele, Brandon F., additional, and Whitby, Denise, additional

Published
2022
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9. Low Levels of Factor H Family Proteins During Meningococcal Disease Indicate Systemic Processes Rather Than Specific Depletion by Neisseria meningitidis

Author

van Beek, Anna E., primary, Pouw, Richard B., additional, Wright, Victoria J., additional, Sallah, Neneh, additional, Inwald, David, additional, Hoggart, Clive, additional, Brouwer, Mieke C., additional, Galassini, Rachel, additional, Thomas, John, additional, Calvo-Bado, Leo, additional, Fink, Colin G., additional, Jongerius, Ilse, additional, Hibberd, Martin, additional, Wouters, Diana, additional, Levin, Michael, additional, and Kuijpers, Taco W., additional

Published
2022
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10. Immunogenic Mycobacterium africanum strains associated with ongoing transmission in The Gambia

Author

Gehre, Florian, Antonio, Martin, Otu, Jacob K., Sallah, Neneh, Secka, Oumie, Faal, Tutty, Owiafe, Patrick, Sutherland, Jayne S., Adetifa, Ifedayo M., Ota, Martin O., Kampmann, Beate, Corrah, Tumani, and de Jong, Bouke C.

Subjects
Gambia -- Health aspects, Mycobacterium -- Genetic aspects, Mycobacteria -- Genetic aspects, Tuberculosis -- Diagnosis -- Care and treatment -- Distribution, Disease transmission -- Research, Company distribution practices, Health
Abstract

Tuberculosis (TB), caused by bacterial pathogens of the Mycobacterium tuberculosis complex (MTBC), is a major global health problem. Sub-Saharan Africa has the highest rate of TB per capita and the [...]

Published
2013
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11. The genomics of heart failure : design and rationale of the HERMES consortium

Author

Lumbers, R. Thomas, Shah, Sonia, Lin, Honghuang, Czuba, Tomasz, Henry, Albert, Swerdlow, Daniel I., Mälarstig, Anders, Andersson, Charlotte, Verweij, Niek, Holmes, Michael V., Ärnlöv, Johan, Svensson, Per, Hemingway, Harry, Sallah, Neneh, Almgren, Peter, Aragam, Krishna G., Asselin, Geraldine, Backman, Joshua D., Biggs, Mary L., Bloom, Heather L., Boersma, Eric, Brandimarto, Jeffrey, Brown, Michael R., Brunner‐La Rocca, Hans‐Peter, Carey, David J., Chaffin, Mark D., Chasman, Daniel I., Chazara, Olympe, Chen, Xing, Chen, Xu, Chung, Jonathan H., Chutkow, William, Cleland, John G.F., Cook, James P., Denus, Simon, Dehghan, Abbas, Delgado, Graciela E., Denaxas, Spiros, Doney, Alexander S., Dörr, Marcus, Dudley, Samuel C., Engström, Gunnar, Esko, Tõnu, Fatemifar, Ghazaleh, Felix, Stephan B., Finan, Chris, Ford, Ian, Fougerousse, Francoise, Fouodjio, René, Ghanbari, Mohsen, Giedraitis, Vilmantas, Lind, Lars, Smith, J. Gustav, Lumbers, R. Thomas, Shah, Sonia, Lin, Honghuang, Czuba, Tomasz, Henry, Albert, Swerdlow, Daniel I., Mälarstig, Anders, Andersson, Charlotte, Verweij, Niek, Holmes, Michael V., Ärnlöv, Johan, Svensson, Per, Hemingway, Harry, Sallah, Neneh, Almgren, Peter, Aragam, Krishna G., Asselin, Geraldine, Backman, Joshua D., Biggs, Mary L., Bloom, Heather L., Boersma, Eric, Brandimarto, Jeffrey, Brown, Michael R., Brunner‐La Rocca, Hans‐Peter, Carey, David J., Chaffin, Mark D., Chasman, Daniel I., Chazara, Olympe, Chen, Xing, Chen, Xu, Chung, Jonathan H., Chutkow, William, Cleland, John G.F., Cook, James P., Denus, Simon, Dehghan, Abbas, Delgado, Graciela E., Denaxas, Spiros, Doney, Alexander S., Dörr, Marcus, Dudley, Samuel C., Engström, Gunnar, Esko, Tõnu, Fatemifar, Ghazaleh, Felix, Stephan B., Finan, Chris, Ford, Ian, Fougerousse, Francoise, Fouodjio, René, Ghanbari, Mohsen, Giedraitis, Vilmantas, Lind, Lars, and Smith, J. Gustav

Abstract

Aims: The HERMES (HEart failure Molecular Epidemiology for Therapeutic targetS) consortium aims to identify the genomic and molecular basis of heart failure. Methods and results: The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34–90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of ≥1.10 for common variants (allele frequency ≥ 0.05) and ≥1.20 for low-frequency variants (allele frequency 0.01–0.05) at P < 5 × 10−8 under an additive genetic model. Conclusions: HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.

Published
2021
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12. The genomics of heart failure:design and rationale of the HERMES consortium

Author

Lumbers, R. Thomas, Shah, Sonia, Lin, Honghuang, Czuba, Tomasz, Henry, Albert, Swerdlow, Daniel I., Mälarstig, Anders, Andersson, Charlotte, Verweij, Niek, Holmes, Michael V., Ärnlöv, Johan, Svensson, Per, Hemingway, Harry, Sallah, Neneh, Almgren, Peter, Aragam, Krishna G., Asselin, Geraldine, Backman, Joshua D., Biggs, Mary L., Bloom, Heather L., Boersma, Eric, Brandimarto, Jeffrey, Brown, Michael R., Brunner-La Rocca, Hans Peter, Carey, David J., Chaffin, Mark D., Chasman, Daniel I., Chazara, Olympe, Chen, Xing, Chen, Xu, Chung, Jonathan H., Chutkow, William, Cleland, John G.F., Cook, James P., de Denus, Simon, Dehghan, Abbas, Delgado, Graciela E., Denaxas, Spiros, Doney, Alexander S., Dörr, Marcus, Dudley, Samuel C., Engström, Gunnar, Esko, Tõnu, Ghanbari, Mohsen, Kardys, Isabella, Kavousi, Maryam, Portilla-Fernandez, Eliana, Teumer, Alexander, Uitterlinden, Andre G., Yang, Jian, Vasan, RS, Smith, JG, Lumbers, R. Thomas, Shah, Sonia, Lin, Honghuang, Czuba, Tomasz, Henry, Albert, Swerdlow, Daniel I., Mälarstig, Anders, Andersson, Charlotte, Verweij, Niek, Holmes, Michael V., Ärnlöv, Johan, Svensson, Per, Hemingway, Harry, Sallah, Neneh, Almgren, Peter, Aragam, Krishna G., Asselin, Geraldine, Backman, Joshua D., Biggs, Mary L., Bloom, Heather L., Boersma, Eric, Brandimarto, Jeffrey, Brown, Michael R., Brunner-La Rocca, Hans Peter, Carey, David J., Chaffin, Mark D., Chasman, Daniel I., Chazara, Olympe, Chen, Xing, Chen, Xu, Chung, Jonathan H., Chutkow, William, Cleland, John G.F., Cook, James P., de Denus, Simon, Dehghan, Abbas, Delgado, Graciela E., Denaxas, Spiros, Doney, Alexander S., Dörr, Marcus, Dudley, Samuel C., Engström, Gunnar, Esko, Tõnu, Ghanbari, Mohsen, Kardys, Isabella, Kavousi, Maryam, Portilla-Fernandez, Eliana, Teumer, Alexander, Uitterlinden, Andre G., Yang, Jian, Vasan, RS, and Smith, JG

Abstract

Aims: The HERMES (HEart failure Molecular Epidemiology for Therapeutic targetS) consortium aims to identify the genomic and molecular basis of heart failure. Methods and results: The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34–90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of ≥1.10 for common variants (allele frequency ≥ 0.05) and ≥1.20 for low-frequency variants (allele frequency 0.01–0.05) at P < 5 × 10−8 under an additive genetic model. Conclusions: HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.

Published
2021

14. Loss of Factor H family proteins associates with meningococcal disease severity

Author

van Beek, Anna E., primary, Pouw, Richard B., additional, Wright, Victoria J., additional, Sallah, Neneh, additional, Inwald, David, additional, Hoggart, Clive, additional, Brouwer, Mieke C., additional, Galassini, Rachel, additional, Thomas, John, additional, Calvo-Bado, Leo, additional, Fink, Colin, additional, Jongerius, Ilse, additional, Hibberd, Martin, additional, Wouters, Diana, additional, Levin, Michael, additional, and Kuijpers, Taco W., additional

Published
2021
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15. High Genotypic Diversity among Rotavirus Strains Infecting Gambian Children

Author

Kwambana, Brenda A., primary, Ikumapayi, Usman N., additional, Sallah, Neneh, additional, Dione, Michel, additional, Jarju, Sheikh, additional, Panchalingham, Sandra, additional, Jafali, James, additional, Lamin, Modou, additional, Betts, Modupeh, additional, Adeyemi, Mitchell, additional, Akinsola, Adebayo, additional, Bittaye, Ousman, additional, Jasseh, Momodou, additional, Kotloff, Karen L., additional, Levine, Myron M., additional, Nataro, James P., additional, Corrah, Tumani, additional, Hossain, M. Jahangir, additional, Saha, Debasish, additional, and Antonio, Martin, additional

Published
2014
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16. ImmunogenicMycobacterium africanumStrains Associated with Ongoing Transmission in The Gambia

Author

Gehre, Florian, primary, Antonio, Martin, additional, Otu, Jacob K., additional, Sallah, Neneh, additional, Secka, Oumie, additional, Faal, Tutty, additional, Owiafe, Patrick, additional, Sutherland, Jayne S., additional, Adetifa, Ifedayo M., additional, Ota, Martin O., additional, Kampmann, Beate, additional, Corrah, Tumani, additional, and de Jong, Bouke C., additional

Published
2013
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17. Chrysomya putoria, a Putative Vector of Diarrheal Diseases

Author

Lindsay, Steven W., primary, Lindsay, Thomas C., additional, Duprez, Jessica, additional, Hall, Martin J. R., additional, Kwambana, Brenda A., additional, Jawara, Musa, additional, Nurudeen, Ikumapayi U., additional, Sallah, Neneh, additional, Wyatt, Nigel, additional, D'Alessandro, Umberto, additional, Pinder, Margaret, additional, and Antonio, Martin, additional

Published
2012
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18. Chrysomya putoria, a Putative Vector of Diarrheal Diseases

Author

Lindsay, Steven W., Lindsay, Thomas C., Duprez, Jessica, Hall, Martin J. R., Kwambana, Brenda A., Jawara, Musa, Nurudeen, Ikumapayi U., Sallah, Neneh, Wyatt, Nigel, D'Alessandro, Umberto, Pinder, Margaret, and Antonio, Martin

Subjects
BLOWFLIES, FECES, DIARRHEA, PATHOGENIC microorganisms, DISEASE vectors
Abstract

Background: Chrysomya spp are common blowflies in Africa, Asia and parts of South America and some species can reproduce in prodigious numbers in pit latrines. Because of their strong association with human feces and their synanthropic nature, we examined whether these flies are likely to be vectors of diarrheal pathogens. Methodology/Principal Findings: Flies were sampled using exit traps placed over the drop holes of latrines in Gambian villages. Odor-baited fly traps were used to determine the relative attractiveness of different breeding and feeding media. The presence of bacteria on flies was confirmed by culture and bacterial DNA identified using PCR. A median of 7.00 flies/latrine/day (IQR = 0.0–25.25) was collected, of which 95% were Chrysomya spp, and of these nearly all were Chrysomya putoria (99%). More flies were collected from traps with feces from young children (median = 3.0, IQR = 1.75–10.75) and dogs (median = 1.50, IQR = 0.0–13.25) than from herbivores (median = 0.0, IQR = 0.0–0.0; goat, horse, cow and calf; p<0.001). Flies were strongly attracted to raw meat (median = 44.5, IQR = 26.25–143.00) compared with fish (median = 0.0, IQR = 0.0–19.75, ns), cooked and uncooked rice, and mangoes (median = 0.0, IQR = 0.0–0.0; p<0.001). Escherichia coli were cultured from the surface of 21% (15/72 agar plates) of Chrysomya spp and 10% of these were enterotoxigenic. Enteroaggregative E. coli were identified by PCR in 2% of homogenized Chrysomya spp, Shigella spp in 1.4% and Salmonella spp in 0.6% of samples. Conclusions/Significance: The large numbers of C. putoria that can emerge from pit latrines, the presence of enteric pathogens on flies, and their strong attraction to raw meat and fish suggests these flies may be common vectors of diarrheal diseases in Africa. [ABSTRACT FROM AUTHOR]

Published
2012
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19. Genome-Wide Sequence Analysis of Kaposi Sarcoma-Associated Herpesvirus Shows Diversification Driven by Recombination

Author

Sallah, Neneh, Palser, Anne L, Watson, Simon J, Labo, Nazzarena, Asiki, Gershim, Marshall, Vickie, Newton, Robert, Whitby, Denise, Kellam, Paul, and Barroso, Inês

Subjects
Adult, Aged, 80 and over, Male, Recombination, Genetic, Adolescent, viruses, virus diseases, Genomics, Sequence Analysis, DNA, biochemical phenomena, metabolism, and nutrition, Middle Aged, 3. Good health, Cohort Studies, Young Adult, DNA, Viral, Herpesvirus 8, Human, Humans, Female, Uganda, Sarcoma, Kaposi, Aged, Genome-Wide Association Study
Abstract

BACKGROUND: Kaposi sarcoma-associated herpesvirus (KSHV) establishes lifelong infection in the human host and has been associated with a variety of malignancies. KSHV displays striking geographic variation in prevalence, which is highest in sub-Saharan Africa. The current KSHV genome sequences available are all tumor cell line-derived or primary tumor-associated viruses, which have provided valuable insights into KSHV genetic diversity. METHODS: Here, we sequenced 45 KSHV genomes from a Ugandan population cohort in which KSHV is endemic; these are the only genome sequences obtained from nondiseased individuals and of KSHV DNA isolated from saliva. RESULTS: Population structure analysis, along with the 25 published genome sequences from other parts of the world, showed whole-genome variation, separating sequences and variation within the central genome contributing to clustering of genomes by geography. We reveal new evidence for the presence of intragenic recombination and multiple recombination events contributing to the divergence of genomes into at least 5 distinct types. DISCUSSION: This study shows that large-scale genome-wide sequencing from clinical and epidemiological samples is necessary to capture the full extent of genetic diversity of KSHV, including recombination, and provides evidence to suggest a revision of KSHV genotype nomenclature.

20. The genomics of heart failure: design and rationale of the HERMES consortium

Author

Lumbers, R. Thomas, Shah, Sonia, Lin, Honghuang, Czuba, Tomasz, Henry, Albert, Swerdlow, Daniel I., Mälarstig, Anders, Andersson, Charlotte, Verweij, Niek, Holmes, Michael V., Ärnlöv, Johan, Svensson, Per, Hemingway, Harry, Sallah, Neneh, Almgren, Peter, Aragam, Krishna G., Asselin, Geraldine, Backman, Joshua D., Biggs, Mary L., Bloom, Heather L., Boersma, Eric, Brandimarto, Jeffrey, Brown, Michael R., Brunner‐La Rocca, Hans‐Peter, Carey, David J., Chaffin, Mark D., Chasman, Daniel I., Chazara, Olympe, Chen, Xing, Chen, Xu, Chung, Jonathan H., Chutkow, William, Cleland, John G.F., Cook, James P., De Denus, Simon, Dehghan, Abbas, Delgado, Graciela E., Denaxas, Spiros, Doney, Alexander S., Dörr, Marcus, Dudley, Samuel C., Engström, Gunnar, Esko, Tõnu, Fatemifar, Ghazaleh, Felix, Stephan B., Finan, Chris, Ford, Ian, Fougerousse, Francoise, Fouodjio, René, Ghanbari, Mohsen, Ghasemi, Sahar, Giedraitis, Vilmantas, Giulianini, Franco, Gottdiener, John S., Gross, Stefan, Guðbjartsson, Daníel F., Gui, Hongsheng, Gutmann, Rebecca, Haggerty, Christopher M., Van Der Harst, Pim, Hedman, Åsa K., Helgadottir, Anna, Hillege, Hans, Hyde, Craig L., Jacob, Jaison, Jukema, J. Wouter, Kamanu, Frederick, Kardys, Isabella, Kavousi, Maryam, Khaw, Kay‐Tee, Kleber, Marcus E., Køber, Lars, Koekemoer, Andrea, Kraus, Bill, Kuchenbaecker, Karoline, Langenberg, Claudia, Lind, Lars, Lindgren, Cecilia M., London, Barry, Lotta, Luca A., Lovering, Ruth C., Luan, Jian'an, Magnusson, Patrik, Mahajan, Anubha, Mann, Douglas, Margulies, Kenneth B., Marston, Nicholas A., März, Winfried, McMurray, John J.V., Melander, Olle, Melloni, Giorgio, Mordi, Ify R., Morley, Michael P., Morris, Andrew D., Morris, Andrew P., Morrison, Alanna C., Nagle, Michael W., Nelson, Christopher P., Newton‐Cheh, Christopher, Niessner, Alexander, Niiranen, Teemu, Nowak, Christoph, O'Donoghue, Michelle L., Owens, Anjali T., Palmer, Colin N.A., Paré, Guillaume, Perola, Markus, Perreault, Louis‐Philippe Lemieux, Portilla‐Fernandez, Eliana, Psaty, Bruce M., Rice, Kenneth M., Ridker, Paul M., Romaine, Simon P.R., Roselli, Carolina, Rotter, Jerome I., Ruff, Christian T., Sabatine, Marc S., Salo, Perttu, Salomaa, Veikko, Van Setten, Jessica, Shalaby, Alaa A., Smelser, Diane T., Smith, Nicholas L., Stefansson, Kari, Stender, Steen, Stott, David J., Sveinbjörnsson, Garðar, Tammesoo, Mari‐Liis, Tardif, Jean‐Claude, Taylor, Kent D., Teder‐Laving, Maris, Teumer, Alexander, Thorgeirsson, Guðmundur, Thorsteinsdottir, Unnur, Torp‐Pedersen, Christian, Trompet, Stella, Tuckwell, Danny, Tyl, Benoit, Uitterlinden, Andre G., Vaura, Felix, Veluchamy, Abirami, Visscher, Peter M., Völker, Uwe, Voors, Adriaan A., Wang, Xiaosong, Wareham, Nicholas J., Weeke, Peter E., Weiss, Raul, White, Harvey D., Wiggins, Kerri L., Xing, Heming, Yang, Jian, Yang, Yifan, Yerges‐Armstrong, Laura M., Yu, Bing, Zannad, Faiez, Zhao, Faye, Regeneron Genetics Center, Wilk, Jemma B., Holm, Hilma, Sattar, Naveed, Lubitz, Steven A., Lanfear, David E., Shah, Svati, Dunn, Michael E., Wells, Quinn S., Asselbergs, Folkert W., Hingorani, Aroon D., Dubé, Marie‐Pierre, Samani, Nilesh J., Lang, Chim C., Cappola, Thomas P., Ellinor, Patrick T., Vasan, Ramachandran S., and Smith, J. Gustav

Subjects
Study Design, Cardiomyopathy, FOS: Biological sciences, Study Designs, Genetics, Heart failure, Biomarkers, 3. Good health, Association studies
Abstract

Funder: Knut and Alice Wallenberg Foundation; Id: http://dx.doi.org/10.13039/501100004063, Funder: Swedish National Health Service, Funder: Skåne University Hospital; Id: http://dx.doi.org/10.13039/501100011077, Funder: Crafoord Foundation; Id: http://dx.doi.org/10.13039/501100003173, Funder: Department of Medicine, Boston University School of Medicine; Id: http://dx.doi.org/10.13039/100008748, Funder: Evans Medical Foundation; Id: http://dx.doi.org/10.13039/100015927, Funder: National Heart, Lung, and Blood Institute; Id: http://dx.doi.org/10.13039/100000050, Funder: British Heart Foundation Cardiovascular Biomedicine, Funder: NIHR UCLH Biomedical Research Centre; Id: http://dx.doi.org/10.13039/501100012317, Aims: The HERMES (HEart failure Molecular Epidemiology for Therapeutic targetS) consortium aims to identify the genomic and molecular basis of heart failure. Methods and results: The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome‐wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow‐up following heart failure diagnosis ranged from 2 to 116 months. Forty‐nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34–90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of ≥1.10 for common variants (allele frequency ≥ 0.05) and ≥1.20 for low‐frequency variants (allele frequency 0.01–0.05) at P < 5 × 10−8 under an additive genetic model. Conclusions: HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.

21. The genomics of heart failure: design and rationale of the HERMES consortium

Author

Lumbers, R Thomas, Shah, Sonia, Lin, Honghuang, Czuba, Tomasz, Henry, Albert, Swerdlow, Daniel I, Mälarstig, Anders, Andersson, Charlotte, Verweij, Niek, Holmes, Michael V, Ärnlöv, Johan, Svensson, Per, Hemingway, Harry, Sallah, Neneh, Almgren, Peter, Aragam, Krishna G, Asselin, Geraldine, Backman, Joshua D, Biggs, Mary L, Bloom, Heather L, Boersma, Eric, Brandimarto, Jeffrey, Brown, Michael R, Brunner-La Rocca, Hans-Peter, Carey, David J, Chaffin, Mark D, Chasman, Daniel I, Chazara, Olympe, Chen, Xing, Chen, Xu, Chung, Jonathan H, Chutkow, William, Cleland, John GF, Cook, James P, De Denus, Simon, Dehghan, Abbas, Delgado, Graciela E, Denaxas, Spiros, Doney, Alexander S, Dörr, Marcus, Dudley, Samuel C, Engström, Gunnar, Esko, Tõnu, Fatemifar, Ghazaleh, Felix, Stephan B, Finan, Chris, Ford, Ian, Fougerousse, Francoise, Fouodjio, René, Ghanbari, Mohsen, Ghasemi, Sahar, Giedraitis, Vilmantas, Giulianini, Franco, Gottdiener, John S, Gross, Stefan, Guðbjartsson, Daníel F, Gui, Hongsheng, Gutmann, Rebecca, Haggerty, Christopher M, Van Der Harst, Pim, Hedman, Åsa K, Helgadottir, Anna, Hillege, Hans, Hyde, Craig L, Jacob, Jaison, Jukema, J Wouter, Kamanu, Frederick, Kardys, Isabella, Kavousi, Maryam, Khaw, Kay-Tee, Kleber, Marcus E, Køber, Lars, Koekemoer, Andrea, Kraus, Bill, Kuchenbaecker, Karoline, Langenberg, Claudia, Lind, Lars, Lindgren, Cecilia M, London, Barry, Lotta, Luca A, Lovering, Ruth C, Luan, Jian'an, Magnusson, Patrik, Mahajan, Anubha, Mann, Douglas, Margulies, Kenneth B, Marston, Nicholas A, März, Winfried, McMurray, John JV, Melander, Olle, Melloni, Giorgio, Mordi, Ify R, Morley, Michael P, Morris, Andrew D, Morris, Andrew P, Morrison, Alanna C, Nagle, Michael W, Nelson, Christopher P, Newton-Cheh, Christopher, Niessner, Alexander, Niiranen, Teemu, Nowak, Christoph, O'Donoghue, Michelle L, Owens, Anjali T, Palmer, Colin NA, Paré, Guillaume, Perola, Markus, Perreault, Louis-Philippe Lemieux, Portilla-Fernandez, Eliana, Psaty, Bruce M, Rice, Kenneth M, Ridker, Paul M, Romaine, Simon PR, Roselli, Carolina, Rotter, Jerome I, Ruff, Christian T, Sabatine, Marc S, Salo, Perttu, Salomaa, Veikko, Van Setten, Jessica, Shalaby, Alaa A, Smelser, Diane T, Smith, Nicholas L, Stefansson, Kari, Stender, Steen, Stott, David J, Sveinbjörnsson, Garðar, Tammesoo, Mari-Liis, Tardif, Jean-Claude, Taylor, Kent D, Teder-Laving, Maris, Teumer, Alexander, Thorgeirsson, Guðmundur, Thorsteinsdottir, Unnur, Torp-Pedersen, Christian, Trompet, Stella, Tuckwell, Danny, Tyl, Benoit, Uitterlinden, Andre G, Vaura, Felix, Veluchamy, Abirami, Visscher, Peter M, Völker, Uwe, Voors, Adriaan A, Wang, Xiaosong, Wareham, Nicholas J, Weeke, Peter E, Weiss, Raul, White, Harvey D, Wiggins, Kerri L, Xing, Heming, Yang, Jian, Yang, Yifan, Yerges-Armstrong, Laura M, Yu, Bing, Zannad, Faiez, Zhao, Faye, Regeneron Genetics Center, Wilk, Jemma B, Holm, Hilma, Sattar, Naveed, Lubitz, Steven A, Lanfear, David E, Shah, Svati, Dunn, Michael E, Wells, Quinn S, Asselbergs, Folkert W, Hingorani, Aroon D, Dubé, Marie-Pierre, Samani, Nilesh J, Lang, Chim C, Cappola, Thomas P, Ellinor, Patrick T, Vasan, Ramachandran S, and Smith, J Gustav

Subjects
Aged, 80 and over, Heart Failure, Male, Cardiomyopathy, Genomics, Middle Aged, 16. Peace & justice, Prognosis, 3. Good health, FOS: Biological sciences, Genetics, Humans, Female, Biomarkers, Association studies, Aged, Genome-Wide Association Study
Abstract

AIMS: The HERMES (HEart failure Molecular Epidemiology for Therapeutic targetS) consortium aims to identify the genomic and molecular basis of heart failure. METHODS AND RESULTS: The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of ≥1.10 for common variants (allele frequency ≥ 0.05) and ≥1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 × 10-8 under an additive genetic model. CONCLUSIONS: HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.

22. Genome-wide host-pathogen analyses reveal genetic interaction points in tuberculosis disease

Author

Jody Phelan, Paula Josefina Gomez-Gonzalez, Nuria Andreu, Yosuke Omae, Licht Toyo-Oka, Hideki Yanai, Reiko Miyahara, Supalert Nedsuwan, Paola Florez de Sessions, Susana Campino, Neneh Sallah, Julian Parkhill, Nat Smittipat, Prasit Palittapongarnpim, Taisei Mushiroda, Michiaki Kubo, Katsushi Tokunaga, Surakameth Mahasirimongkol, Martin L. Hibberd, Taane G. Clark, Phelan, Jody [0000-0001-8323-7019], Toyo-Oka, Licht [0000-0002-9738-2441], Campino, Susana [0000-0003-1403-6138], Sallah, Neneh [0000-0002-2953-5311], Parkhill, Julian [0000-0002-7069-5958], Kubo, Michiaki [0000-0002-0095-2322], Hibberd, Martin L [0000-0001-8587-1849], Clark, Taane G [0000-0001-8985-9265], and Apollo - University of Cambridge Repository

Subjects
Multidisciplinary, Genome, Host-Pathogen Interactions, General Physics and Astronomy, Humans, Tuberculosis, General Chemistry, Mycobacterium tuberculosis, General Biochemistry, Genetics and Molecular Biology, Phylogeny, Genome-Wide Association Study
Abstract

The genetics underlying tuberculosis (TB) pathophysiology are poorly understood. Human genome-wide association studies have failed so far to reveal reproducible susceptibility loci, attributed in part to the influence of the underlying Mycobacterium tuberculosis (Mtb) bacterial genotype on the outcome of the infection. Several studies have found associations of human genetic polymorphisms with Mtb phylo-lineages, but studies analysing genome-genome interactions are needed. By implementing a phylogenetic tree-based Mtb-to-human analysis for 714 TB patients from Thailand, we identify eight putative genetic interaction points (P −8) including human loci DAP and RIMS3, both linked to the IFNγ cytokine and host immune system, as well as FSTL5, previously associated with susceptibility to TB. Many of the corresponding Mtb markers are lineage specific. The genome-to-genome analysis reveals a complex interactome picture, supports host-pathogen adaptation and co-evolution in TB, and has potential applications to large-scale studies across many TB endemic populations matched for host-pathogen genomic diversity.

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

Author

Denise Whitby, Alexander T. Dilthey, Deepti Gurdasani, Martin L. Hibberd, Wendell Miley, Manjinder S. Sandhu, Cristina Pomilla, Paul Kellam, Nazzarena Labo, Robert U. Newton, Gershim Asiki, Elena M. Cornejo Castro, Vickie Marshall, Alexander J. Mentzer, Elizabeth H. Young, Martin O. Pollard, Inês Barroso, Neneh Sallah, Tommy Carstensen, Segun Fatumo, Sallah, Neneh [0000-0002-2953-5311], Pollard, Martin O [0000-0001-8738-0920], Dilthey, Alexander T [0000-0002-6394-4581], Mentzer, Alexander J [0000-0002-4502-2209], Cornejo Castro, Elena M [0000-0003-1480-1397], Asiki, Gershim [0000-0002-9966-1153], Hibberd, Martin L [0000-0001-8587-1849], Sandhu, Manjinder [0000-0002-2725-142X], Kellam, Paul [0000-0003-3166-4734], Barroso, Inês [0000-0001-5800-4520], Apollo - University of Cambridge Repository, Pollard, Martin O. [0000-0001-8738-0920], Dilthey, Alexander T. [0000-0002-6394-4581], Mentzer, Alexander J. [0000-0002-4502-2209], Cornejo Castro, Elena M. [0000-0003-1480-1397], and Hibberd, Martin L. [0000-0001-8587-1849]

Subjects
0301 basic medicine, Male, Rural Population, Epstein-Barr Virus Infections, Herpesvirus 4, Human, Urban Population, viruses, 45/43, General Physics and Astronomy, Gene Expression, Genome-wide association study, Disease, Antibodies, Viral, 0302 clinical medicine, hemic and lymphatic diseases, Uganda, lcsh:Science, Antigens, Viral, Disease Resistance, Henipavirus Infections, Multidisciplinary, 631/208/729, Transmission (medicine), Coinfection, Incidence, virus diseases, Genomics, 631/208/721, 631/208/248, Middle Aged, 631/208/727, 030220 oncology & carcinogenesis, 631/208/212, Herpesvirus 8, Human, Host-Pathogen Interactions, Female, 82/1, 141, Adult, HIV Positivity, Genotype, Adolescent, Science, 45/23, Human leukocyte antigen, Biology, General Biochemistry, Genetics and Molecular Biology, Virus, Article, HLA-DQ alpha-Chains, 03 medical and health sciences, Antigen, medicine, Immunogenetics, Humans, Sarcoma, Kaposi, HIV, General Chemistry, medicine.disease, 030104 developmental biology, Epstein-Barr Virus Nuclear Antigens, Immunology, Genetic markers, lcsh:Q, Heritable quantitative trait, Capsid Proteins, Genome-Wide Association Study
Abstract

Kaposi’s sarcoma-associated herpesvirus (KSHV) and Epstein-Barr Virus (EBV) establish life-long infections and are associated with malignancies. Striking geographic variation in incidence and the fact that virus alone is insufficient to cause disease, suggests other co-factors are involved. Here we present epidemiological analysis and genome-wide association study (GWAS) in 4365 individuals from an African population cohort, to assess the influence of host genetic and non-genetic factors on virus antibody responses. EBV/KSHV co-infection (OR = 5.71(1.58–7.12)), HIV positivity (OR = 2.22(1.32–3.73)) and living in a more rural area (OR = 1.38(1.01–1.89)) are strongly associated with immunogenicity. GWAS reveals associations with KSHV antibody response in the HLA-B/C region (p = 6.64 × 10−09). For EBV, associations are identified for VCA (rs71542439, p = 1.15 × 10−12). Human leucocyte antigen (HLA) and trans-ancestry fine-mapping substantiate that distinct variants in HLA-DQA1 (p = 5.24 × 10−44) are driving associations for EBNA-1 in Africa. This study highlights complex interactions between KSHV and EBV, in addition to distinct genetic architectures resulting in important differences in pathogenesis and transmission., Disease prognosis after infection with Kaposi’s sarcoma-associated herpesvirus and Epstein-Barr Virus is highly variable. Here the authors carry out epidemiological and genetic analysis of a Ugandan cohort and suggest complex interactions may influence pathogenesis and transmission.

Published
2020

24. The genomics of heart failure: design and rationale of the HERMES consortium.

Author

Lumbers RT, Shah S, Lin H, Czuba T, Henry A, Swerdlow DI, Mälarstig A, Andersson C, Verweij N, Holmes MV, Ärnlöv J, Svensson P, Hemingway H, Sallah N, Almgren P, Aragam KG, Asselin G, Backman JD, Biggs ML, Bloom HL, Boersma E, Brandimarto J, Brown MR, Brunner-La Rocca HP, Carey DJ, Chaffin MD, Chasman DI, Chazara O, Chen X, Chen X, Chung JH, Chutkow W, Cleland JGF, Cook JP, de Denus S, Dehghan A, Delgado GE, Denaxas S, Doney AS, Dörr M, Dudley SC, Engström G, Esko T, Fatemifar G, Felix SB, Finan C, Ford I, Fougerousse F, Fouodjio R, Ghanbari M, Ghasemi S, Giedraitis V, Giulianini F, Gottdiener JS, Gross S, Guðbjartsson DF, Gui H, Gutmann R, Haggerty CM, van der Harst P, Hedman ÅK, Helgadottir A, Hillege H, Hyde CL, Jacob J, Jukema JW, Kamanu F, Kardys I, Kavousi M, Khaw KT, Kleber ME, Køber L, Koekemoer A, Kraus B, Kuchenbaecker K, Langenberg C, Lind L, Lindgren CM, London B, Lotta LA, Lovering RC, Luan J, Magnusson P, Mahajan A, Mann D, Margulies KB, Marston NA, März W, McMurray JJV, Melander O, Melloni G, Mordi IR, Morley MP, Morris AD, Morris AP, Morrison AC, Nagle MW, Nelson CP, Newton-Cheh C, Niessner A, Niiranen T, Nowak C, O'Donoghue ML, Owens AT, Palmer CNA, Paré G, Perola M, Perreault LL, Portilla-Fernandez E, Psaty BM, Rice KM, Ridker PM, Romaine SPR, Roselli C, Rotter JI, Ruff CT, Sabatine MS, Salo P, Salomaa V, van Setten J, Shalaby AA, Smelser DT, Smith NL, Stefansson K, Stender S, Stott DJ, Sveinbjörnsson G, Tammesoo ML, Tardif JC, Taylor KD, Teder-Laving M, Teumer A, Thorgeirsson G, Thorsteinsdottir U, Torp-Pedersen C, Trompet S, Tuckwell D, Tyl B, Uitterlinden AG, Vaura F, Veluchamy A, Visscher PM, Völker U, Voors AA, Wang X, Wareham NJ, Weeke PE, Weiss R, White HD, Wiggins KL, Xing H, Yang J, Yang Y, Yerges-Armstrong LM, Yu B, Zannad F, Zhao F, Wilk JB, Holm H, Sattar N, Lubitz SA, Lanfear DE, Shah S, Dunn ME, Wells QS, Asselbergs FW, Hingorani AD, Dubé MP, Samani NJ, Lang CC, Cappola TP, Ellinor PT, Vasan RS, and Smith JG

Subjects
Aged, Aged, 80 and over, Female, Genomics, Humans, Male, Middle Aged, Prognosis, Genome-Wide Association Study, Heart Failure genetics
Abstract

Aims: The HERMES (HEart failure Molecular Epidemiology for Therapeutic targetS) consortium aims to identify the genomic and molecular basis of heart failure., Methods and Results: The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of ≥1.10 for common variants (allele frequency ≥ 0.05) and ≥1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 × 10 -8 under an additive genetic model., Conclusions: HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Published
2021
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