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5. Genetic effects on the timing of parturition and links to fetal birth weight

Author

Solé-Navais, Pol, Flatley, Christopher, Steinthorsdottir, Valgerdur, Vaudel, Marc, Juodakis, Julius, Chen, Jing, Laisk, Triin, LaBella, Abigail L., Westergaard, David, Bacelis, Jonas, Brumpton, Ben, Skotte, Line, Borges, Maria C., Helgeland, Øyvind, Mahajan, Anubha, Wielscher, Matthias, Lin, Frederick, Briggs, Catherine, Wang, Carol A., Moen, Gunn-Helen, Beaumont, Robin N., Bradfield, Jonathan P., Abraham, Abin, Thorleifsson, Gudmar, Gabrielsen, Maiken E., Ostrowski, Sisse R., Modzelewska, Dominika, Nohr, Ellen A., Hypponen, Elina, Srivastava, Amit, Talbot, Octavious, Allard, Catherine, Williams, Scott M., Menon, Ramkumar, Shields, Beverley M., Sveinbjornsson, Gardar, Xu, Huan, Melbye, Mads, Lowe, Jr, William, Bouchard, Luigi, Oken, Emily, Pedersen, Ole B., Gudbjartsson, Daniel F., Erikstrup, Christian, Sørensen, Erik, Lie, Rolv T., Teramo, Kari, Hallman, Mikko, Juliusdottir, Thorhildur, Hakonarson, Hakon, Ullum, Henrik, Hattersley, Andrew T., Sletner, Line, Merialdi, Mario, Rifas-Shiman, Sheryl L., Steingrimsdottir, Thora, Scholtens, Denise, Power, Christine, West, Jane, Nyegaard, Mette, Capra, John A., Skogholt, Anne H., Magnus, Per, Andreassen, Ole A., Thorsteinsdottir, Unnur, Grant, Struan F. A., Qvigstad, Elisabeth, Pennell, Craig E., Hivert, Marie-France, Hayes, Geoffrey M., Jarvelin, Marjo-Riitta, McCarthy, Mark I., Lawlor, Deborah A., Nielsen, Henriette S., Mägi, Reedik, Rokas, Antonis, Hveem, Kristian, Stefansson, Kari, Feenstra, Bjarke, Njolstad, Pål, Muglia, Louis J., Freathy, Rachel M., Johansson, Stefan, Zhang, Ge, and Jacobsson, Bo

Published
2023
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7. A multi-cohort genome-wide association study in African ancestry individuals reveals risk loci for primary open-angle glaucoma

Author

Verma, Shefali S., Gudiseva, Harini V., Chavali, Venkata R.M., Salowe, Rebecca J., Bradford, Yuki, Guare, Lindsay, Lucas, Anastasia, Collins, David W., Vrathasha, Vrathasha, Nair, Rohini M., Rathi, Sonika, Zhao, Bingxin, He, Jie, Lee, Roy, Zenebe-Gete, Selam, Bowman, Anita S., McHugh, Caitlin P., Zody, Michael C., Pistilli, Maxwell, Khachatryan, Naira, Daniel, Ebenezer, Murphy, Windell, Henderer, Jeffrey, Kinzy, Tyler G., Iyengar, Sudha K., Peachey, Neal S., Taylor, Kent D., Guo, Xiuqing, Chen, Yii-Der Ida, Zangwill, Linda, Girkin, Christopher, Ayyagari, Radha, Liebmann, Jeffrey, Chuka-Okosa, Chimd M., Williams, Susan E., Akafo, Stephen, Budenz, Donald L., Olawoye, Olusola O., Ramsay, Michele, Ashaye, Adeyinka, Akpa, Onoja M., Aung, Tin, Wiggs, Janey L., Ross, Ahmara G., Cui, Qi N., Addis, Victoria, Lehman, Amanda, Miller-Ellis, Eydie, Sankar, Prithvi S., Williams, Scott M., Ying, Gui-shuang, Cooke Bailey, Jessica, Rotter, Jerome I., Weinreb, Robert, Khor, Chiea Chuen, Hauser, Michael A., Ritchie, Marylyn D., and O’Brien, Joan M.

Published
2024
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14. Author Correction: Genetic effects on the timing of parturition and links to fetal birth weight

Author

Solé-Navais, Pol, Flatley, Christopher, Steinthorsdottir, Valgerdur, Vaudel, Marc, Juodakis, Julius, Chen, Jing, Laisk, Triin, LaBella, Abigail L., Westergaard, David, Bacelis, Jonas, Brumpton, Ben, Skotte, Line, Borges, Maria C., Helgeland, Øyvind, Mahajan, Anubha, Wielscher, Matthias, Lin, Frederick, Briggs, Catherine, Wang, Carol A., Moen, Gunn-Helen, Beaumont, Robin N., Bradfield, Jonathan P., Abraham, Abin, Thorleifsson, Gudmar, Gabrielsen, Maiken E., Ostrowski, Sisse R., Modzelewska, Dominika, Nohr, Ellen A., Hypponen, Elina, Srivastava, Amit, Talbot, Octavious, Allard, Catherine, Williams, Scott M., Menon, Ramkumar, Shields, Beverley M., Sveinbjornsson, Gardar, Xu, Huan, Melbye, Mads, Lowe, Jr, William, Bouchard, Luigi, Oken, Emily, Pedersen, Ole B., Gudbjartsson, Daniel F., Erikstrup, Christian, Sørensen, Erik, Lie, Rolv T., Teramo, Kari, Hallman, Mikko, Juliusdottir, Thorhildur, Hakonarson, Hakon, Ullum, Henrik, Hattersley, Andrew T., Sletner, Line, Merialdi, Mario, Rifas-Shiman, Sheryl L., Steingrimsdottir, Thora, Scholtens, Denise, Power, Christine, West, Jane, Nyegaard, Mette, Capra, John A., Skogholt, Anne H., Magnus, Per, Andreassen, Ole A., Thorsteinsdottir, Unnur, Grant, Struan F. A., Qvigstad, Elisabeth, Pennell, Craig E., Hivert, Marie-France, Hayes, Geoffrey M., Jarvelin, Marjo-Riitta, McCarthy, Mark I., Lawlor, Deborah A., Nielsen, Henriette S., Mägi, Reedik, Rokas, Antonis, Hveem, Kristian, Stefansson, Kari, Feenstra, Bjarke, Njolstad, Pål, Muglia, Louis J., Freathy, Rachel M., Johansson, Stefan, Zhang, Ge, and Jacobsson, Bo

Published
2023
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17. Causal Effect of Plasminogen Activator Inhibitor Type 1 on Coronary Heart Disease

Author

Song, Ci, Burgess, Stephen, Eicher, John D, O'Donnell, Christopher J, Johnson, Andrew D, Huang, Jie, Sabater‐Lleal, Maria, Asselbergs, Folkert W, Tregouet, David, Shin, So‐Youn, Ding, Jingzhong, Baumert, Jens, Oudot‐Mellakh, Tiphaine, Folkersen, Lasse, Smith, Nicholas L, Williams, Scott M, Ikram, Mohammad A, Kleber, Marcus E, Becker, Diane M, Truong, Vinh, Mychaleckyj, Josyf C, Tang, Weihong, Yang, Qiong, Sennblad, Bengt, Moore, Jason H, Williams, Frances MK, Dehghan, Abbas, Silbernagel, Günther, Schrijvers, Elisabeth MC, Smith, Shelly, Karakas, Mahir, Tofler, Geoffrey H, Silveira, Angela, Navis, Gerjan J, Lohman, Kurt, Chen, Ming‐Huei, Peters, Annette, Goel, Anuj, Hopewell, Jemma C, Chambers, John C, Saleheen, Danish, Lundmark, Per, Psaty, Bruce M, Strawbridge, Rona J, Boehm, Bernhard O, Carter, Angela M, Meisinger, Christa, Peden, John F, Bis, Joshua C, McKnight, Barbara, Öhrvik, John, Taylor, Kent, Franzosi, Maria Grazia, Seedorf, Udo, Collins, Rory, Franco‐Cereceda, Anders, Syvänen, Ann‐Christine, Goodall, Alison H, Yanek, Lisa R, Cushman, Mary, Müller‐Nurasyid, Martina, Folsom, Aaron R, Basu, Saonli, Matijevic, Nena, van Gilst, Wiek H, Kooner, Jaspal S, Hofman, Albert, Danesh, John, Clarke, Robert, Meigs, James B, Kathiresan, Sekar, Reilly, Muredach P, Klopp, Norman, Harris, Tamara B, Winkelmann, Bernhard R, Grant, Peter J, Hillege, Hans L, Watkins, Hugh, Spector, Timothy D, Becker, Lewis C, Tracy, Russell P, März, Winfried, Uitterlinden, Andre G, Eriksson, Per, Cambien, Francois, Morange, Pierre‐Emmanuel, Koenig, Wolfgang, Soranzo, Nicole, van der Harst, Pim, Liu, Yongmei, Hamsten, Anders, Ehret, Georg B, Munroe, Patricia B, Rice, Kenneth M, Bochud, Murielle, Chasman, Daniel I, Smith, Albert V, Tobin, Martin D, and Verwoert, Germaine C

Subjects
Clinical Research, Heart Disease - Coronary Heart Disease, Cardiovascular, Heart Disease, Aging, Biomarkers, Blood Glucose, Coronary Disease, Fibrinolysis, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Incidence, Lipoproteins, HDL, Mendelian Randomization Analysis, Multivariate Analysis, Observational Studies as Topic, Odds Ratio, Plasminogen Activator Inhibitor 1, Polymorphism, Single Nucleotide, Risk Assessment, Risk Factors, coronary heart disease, genome-wide association study, Mendelian randomization, plasminogen activator inhibitor type 1, single nucleotide polymorphism, genome‐wide association study, Cardiorespiratory Medicine and Haematology
Abstract

Plasminogen activator inhibitor type 1 (PAI-1) plays an essential role in the fibrinolysis system and thrombosis. Population studies have reported that blood PAI-1 levels are associated with increased risk of coronary heart disease (CHD). However, it is unclear whether the association reflects a causal influence of PAI-1 on CHD risk. To evaluate the association between PAI-1 and CHD, we applied a 3-step strategy. First, we investigated the observational association between PAI-1 and CHD incidence using a systematic review based on a literature search for PAI-1 and CHD studies. Second, we explored the causal association between PAI-1 and CHD using a Mendelian randomization approach using summary statistics from large genome-wide association studies. Finally, we explored the causal effect of PAI-1 on cardiovascular risk factors including metabolic and subclinical atherosclerosis measures. In the systematic meta-analysis, the highest quantile of blood PAI-1 level was associated with higher CHD risk comparing with the lowest quantile (odds ratio=2.17; 95% CI: 1.53, 3.07) in an age- and sex-adjusted model. The effect size was reduced in studies using a multivariable-adjusted model (odds ratio=1.46; 95% CI: 1.13, 1.88). The Mendelian randomization analyses suggested a causal effect of increased PAI-1 level on CHD risk (odds ratio=1.22 per unit increase of log-transformed PAI-1; 95% CI: 1.01, 1.47). In addition, we also detected a causal effect of PAI-1 on elevating blood glucose and high-density lipoprotein cholesterol. Our study indicates a causal effect of elevated PAI-1 level on CHD risk, which may be mediated by glucose dysfunction.

Published
2017

19. Transdisciplinary approaches enhance the production of translational knowledge

Author

Ciesielski, Timothy H, Aldrich, Melinda C, Marsit, Carmen J, Hiatt, Robert A, and Williams, Scott M

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Clinical Sciences, Biological Sciences, Clinical Research, Generic health relevance, Animals, Decision Making, Epidemiologists, Humans, Interdisciplinary Communication, Models, Biological, Translational Research, Biomedical, Translational Medical Research, General Clinical Medicine, Biochemistry and cell biology, Clinical sciences
Abstract

The primary goal of translational research is to generate and apply knowledge that can improve human health. Although research conducted within the confines of a single discipline has helped us to achieve this goal in many settings, this unidisciplinary approach may not be optimal when disease causation is complex and health decisions are pressing. To address these issues, we suggest that transdisciplinary approaches can facilitate the progress of translational research, and we review publications that demonstrate what these approaches can look like. These examples serve to (1) demonstrate why transdisciplinary research is useful, and (2) stimulate a conversation about how it can be further promoted. While we note that open-minded communication is a prerequisite for germinating any transdisciplinary work and that epidemiologists can play a key role in promoting it, we do not propose a rigid protocol for conducting transdisciplinary research, as one really does not exist. These achievements were developed in settings where typical disciplinary and institutional barriers were surmountable, but they were not accomplished with a single predetermined plan. The benefits of cross-disciplinary communication are hard to predict a priori and a detailed research protocol or process may impede the realization of novel and important insights. Overall, these examples demonstrate that enhanced cross-disciplinary information exchange can serve as a starting point that helps researchers frame better questions, integrate more relevant evidence, and advance translational knowledge more effectively. Specifically, we discuss examples where transdisciplinary approaches are helping us to better explore, assess, and intervene to improve human health.

Published
2017

21. The African Society of Human Genetics successfully launches global data science workshops

Author

Nembaware, Victoria, primary, Bennett, Declan, additional, Chimusa, Emile R., additional, Chikowore, Tinashe, additional, Daodu, Richard, additional, Bitoungui, Valential Ngo, additional, Williams, Scott M., additional, Fatumo, Segun, additional, Healy, Sandra, additional, Seoighe, Cathal, additional, Wonkam, Ambroise, additional, Landouré, Guida, additional, Ndiaye, Rokhaya, additional, Dandara, Collet, additional, Mutesa, Leon, additional, Ramsay, Michele, additional, El-Kamah, Ghada, additional, Sirugo, Giorgio, additional, Makani, Julie, additional, Sadki, Khalid, additional, Alimohamed, Mohamed Zahir, additional, Nkya, Siana, additional, Gaye, Amadou, additional, Ramesar, Raj, additional, Choudhury, Ananyo, additional, Happi, Christian, additional, Munung, Nchangwi Syntia, additional, Kherji, Nadia, additional, Hotchkiss, Jade, additional, Ras, Verena, additional, Ghansay, Anita, additional, Musanabaganwa, Clarisse, additional, Esoh, Kevin Kum, additional, Adadey, Samuel Mawuli, additional, and Coughlan, Simone Christina, additional

Published
2023
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27. Genome-wide Association Analysis of Blood-Pressure Traits in African-Ancestry Individuals Reveals Common Associated Genes in African and Non-African Populations

Author

Franceschini, Nora, Fox, Ervin, Zhang, Zhaogong, Edwards, Todd L, Nalls, Michael A, Sung, Yun Ju, Tayo, Bamidele O, Sun, Yan V, Gottesman, Omri, Adeyemo, Adebawole, Johnson, Andrew D, Young, J Hunter, Rice, Ken, Duan, Qing, Chen, Fang, Li, Yun, Tang, Hua, Fornage, Myriam, Keene, Keith L, Andrews, Jeanette S, Smith, Jennifer A, Faul, Jessica D, Guangfa, Zhang, Guo, Wei, Liu, Yu, Murray, Sarah S, Musani, Solomon K, Srinivasan, Sathanur, Edwards, Digna R Velez, Wang, Heming, Becker, Lewis C, Bovet, Pascal, Bochud, Murielle, Broeckel, Ulrich, Burnier, Michel, Carty, Cara, Chasman, Daniel I, Ehret, Georg, Chen, Wei-Min, Chen, Guanjie, Chen, Wei, Ding, Jingzhong, Dreisbach, Albert W, Evans, Michele K, Guo, Xiuqing, Garcia, Melissa E, Jensen, Rich, Keller, Margaux F, Lettre, Guillaume, Lotay, Vaneet, Martin, Lisa W, Moore, Jason H, Morrison, Alanna C, Mosley, Thomas H, Ogunniyi, Adesola, Palmas, Walter, Papanicolaou, George, Penman, Alan, Polak, Joseph F, Ridker, Paul M, Salako, Babatunde, Singleton, Andrew B, Shriner, Daniel, Taylor, Kent D, Vasan, Ramachandran, Wiggins, Kerri, Williams, Scott M, Yanek, Lisa R, Zhao, Wei, Zonderman, Alan B, Becker, Diane M, Berenson, Gerald, Boerwinkle, Eric, Bottinger, Erwin, Cushman, Mary, Eaton, Charles, Nyberg, Fredrik, Heiss, Gerardo, Hirschhron, Joel N, Howard, Virginia J, Karczewsk, Konrad J, Lanktree, Matthew B, Liu, Kiang, Liu, Yongmei, Loos, Ruth, Margolis, Karen, Snyder, Michael, Consortium, the Asian Genetic Epidemiology Network, Go, Min Jin, Kim, Young Jin, Lee, Jong-Young, Jeon, Jae-Pil, Kim, Sung Soo, Han, Bok-Ghee, Cho, Yoon Shin, Sim, Xueling, Tay, Wan Ting, Ong, Rick Twee Hee, Seielstad, Mark, and Liu, Jian Jun

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Cardiovascular, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Africa, Black People, Blood Pressure, Cohort Studies, Databases, Genetic, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Quantitative Trait, Heritable, Reproducibility of Results, Asian Genetic Epidemiology Network Consortium, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

High blood pressure (BP) is more prevalent and contributes to more severe manifestations of cardiovascular disease (CVD) in African Americans than in any other United States ethnic group. Several small African-ancestry (AA) BP genome-wide association studies (GWASs) have been published, but their findings have failed to replicate to date. We report on a large AA BP GWAS meta-analysis that includes 29,378 individuals from 19 discovery cohorts and subsequent replication in additional samples of AA (n = 10,386), European ancestry (EA) (n = 69,395), and East Asian ancestry (n = 19,601). Five loci (EVX1-HOXA, ULK4, RSPO3, PLEKHG1, and SOX6) reached genome-wide significance (p < 1.0 × 10(-8)) for either systolic or diastolic BP in a transethnic meta-analysis after correction for multiple testing. Three of these BP loci (EVX1-HOXA, RSPO3, and PLEKHG1) lack previous associations with BP. We also identified one independent signal in a known BP locus (SOX6) and provide evidence for fine mapping in four additional validated BP loci. We also demonstrate that validated EA BP GWAS loci, considered jointly, show significant effects in AA samples. Consequently, these findings suggest that BP loci might have universal effects across studied populations, demonstrating that multiethnic samples are an essential component in identifying, fine mapping, and understanding their trait variability.

Published
2013

35. Evidence of epistasis in regions of long-range linkage disequilibrium across five complex diseases in the UK Biobank and eMERGE datasets

Author

Singhal, Pankhuri, primary, Veturi, Yogasudha, additional, Dudek, Scott M., additional, Lucas, Anastasia, additional, Frase, Alex, additional, van Steen, Kristel, additional, Schrodi, Steven J., additional, Fasel, David, additional, Weng, Chunhua, additional, Pendergrass, Rion, additional, Schaid, Daniel J., additional, Kullo, Iftikhar J., additional, Dikilitas, Ozan, additional, Sleiman, Patrick M.A., additional, Hakonarson, Hakon, additional, Moore, Jason H., additional, Williams, Scott M., additional, Ritchie, Marylyn D., additional, and Verma, Shefali S., additional

Published
2023
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39. Supplementary Data from The Cytochrome P450 Slow Metabolizers CYP2C9*2 and CYP2C9*3 Directly Regulate Tumorigenesis via Reduced Epoxyeicosatrienoic Acid Production

Author

Sausville, Lindsay N., primary, Gangadhariah, Mahesha H., primary, Chiusa, Manuel, primary, Mei, Shaojun, primary, Wei, Shouzuo, primary, Zent, Roy, primary, Luther, James M., primary, Shuey, Megan M., primary, Capdevila, Jorge H., primary, Falck, John R., primary, Guengerich, F. Peter, primary, Williams, Scott M., primary, and Pozzi, Ambra, primary

Published
2023
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40. Data from The Cytochrome P450 Slow Metabolizers CYP2C9*2 and CYP2C9*3 Directly Regulate Tumorigenesis via Reduced Epoxyeicosatrienoic Acid Production

Author

Sausville, Lindsay N., primary, Gangadhariah, Mahesha H., primary, Chiusa, Manuel, primary, Mei, Shaojun, primary, Wei, Shouzuo, primary, Zent, Roy, primary, Luther, James M., primary, Shuey, Megan M., primary, Capdevila, Jorge H., primary, Falck, John R., primary, Guengerich, F. Peter, primary, Williams, Scott M., primary, and Pozzi, Ambra, primary

Published
2023
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43. G Protein-Coupled Receptor Kinase 4 Gene Variants in Human Essential Hypertension

Author

Felder, Robin A., Sanada, Hironobu, Xu, Jing, Yu, Pei-Ying, Wang, Zheng, Watanabe, Hidetsuna, Asico, Laureano D., Wang, Wei, Zheng, Shaopeng, Yamaguchi, Ikuyo, Williams, Scott M., Gainer, James, Brown, Nancy J., Hazen-Martin, Debra, Wong, Lee-Jun C., Robillard, Jean E., Carey, Robert M., Eisner, Gilbert M., and Jose, Pedro A.

Published
2002

46. The quagmire of race, genetic ancestry, and health disparities

Author

Sirugo, Giorgio, Tishkoff, Sarah A., and Williams, Scott M.

Subjects
Race -- Health aspects, Equality -- Health aspects, Heredity -- Health aspects, Health care industry
Abstract

The debate on human categorization based on 'race,' its relationship to genetic variation among populations, and its scientific legitimacy has been raging for decades. Yet, there is still no clear [...]

Published
2021
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