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1,378 results on '"Rexrode, Kathryn M"'

1. Lipidome changes due to improved dietary fat quality inform cardiometabolic risk reduction and precision nutrition

Author

Eichelmann, Fabian, Prada, Marcela, Sellem, Laury, Jackson, Kim G., Salas Salvadó, Jordi, Razquin Burillo, Cristina, Estruch, Ramon, Friedén, Michael, Rosqvist, Frederik, Risérus, Ulf, Rexrode, Kathryn M., Guasch-Ferré, Marta, Sun, Qi, Willett, Walter C., Martinez-Gonzalez, Miguel Angel, Lovegrove, Julie A., Hu, Frank B., Schulze, Matthias B., and Wittenbecher, Clemens

Published
2024
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3. 2024 Guideline for the Primary Prevention of Stroke: A Guideline From the American Heart Association/American Stroke Association

Author

Bushnell, Cheryl, Kernan, Walter N., Sharrief, Anjail Z., Chaturvedi, Seemant, Cole, John W., Cornwell, William K., III, Cosby-Gaither, Christine, Doyle, Sarah, Goldstein, Larry B., Lennon, Olive, Levine, Deborah A., Love, Mary, Miller, Eliza, Nguyen-Huynh, Mai, Rasmussen-Winkler, Jennifer, Rexrode, Kathryn M., Rosendale, Nicole, Sarma, Satyam, Shimbo, Daichi, Simpkins, Alexis N., Spatz, Erica S., Sun, Lisa R., Tangpricha, Vin, Turnage, Dawn, Velazquez, Gabriela, and Whelton, Paul

Published
2024
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4. Differences in Metabolomic Profiles Between Black and White Women and Risk of Coronary Heart Disease: an Observational Study of Women From Four US Cohorts

Author

Hu, Jie, Yao, Jie, Deng, Shuliang, Balasubramanian, Raji, Jiménez, Monik C, Li, Jun, Guo, Xiuqing, Cruz, Daniel E, Gao, Yan, Huang, Tianyi, Zeleznik, Oana A, Ngo, Debby, Liu, Simin, Rosal, Milagros C, Nassir, Rami, Paynter, Nina P, Albert, Christine M, Tracy, Russell P, Durda, Peter, Liu, Yongmei, Taylor, Kent D, Johnson, W Craig, Sun, Qi, Rimm, Eric B, Eliassen, A Heather, Rich, Stephen S, Rotter, Jerome I, Gerszten, Robert E, Clish, Clary B, and Rexrode, Kathryn M

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Heart Disease - Coronary Heart Disease, Atherosclerosis, Aging, Cardiovascular, Prevention, Clinical Research, Heart Disease, Good Health and Well Being, Amino Acids, Coronary Disease, Female, Hormones, Humans, Lipids, Risk Factors, United States, heart diseases, health status disparities, metabolomics, plasma, race, women, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences
Abstract

BackgroundRacial differences in metabolomic profiles may reflect underlying differences in social determinants of health by self-reported race and may be related to racial disparities in coronary heart disease (CHD) among women in the United States. However, the magnitude of differences in metabolomic profiles between Black and White women in the United States has not been well-described. It also remains unknown whether such differences are related to differences in CHD risk.MethodsPlasma metabolomic profiles were analyzed using liquid chromatography-tandem mass spectrometry in the WHI-OS (Women's Health Initiative-Observational Study; 138 Black and 696 White women), WHI-HT trials (WHI-Hormone Therapy; 156 Black and 1138 White women), MESA (Multi-Ethnic Study of Atherosclerosis; 114 Black and 219 White women), JHS (Jackson Heart Study; 1465 Black women with 107 incident CHD cases), and NHS (Nurses' Health Study; 2506 White women with 136 incident CHD cases). First, linear regression models were used to estimate associations between self-reported race and 472 metabolites in WHI-OS (discovery); findings were replicated in WHI-HT and validated in MESA. Second, we used elastic net regression to construct a racial difference metabolomic pattern (RDMP) representing differences in the metabolomic patterns between Black and White women in the WHI-OS; the RDMP was validated in the WHI-HT and MESA. Third, using conditional logistic regressions in the WHI (717 CHD cases and 719 matched controls), we examined associations of metabolites with large differences in levels by race and the RDMP with risk of CHD, and the results were replicated in Black women from the JHS and White women from the NHS.ResultsOf the 472 tested metabolites, levels of 259 (54.9%) metabolites, mostly lipid metabolites and amino acids, significantly differed between Black and White women in both WHI-OS and WHI-HT after adjusting for baseline characteristics, socioeconomic status, lifestyle factors, baseline health conditions, and medication use (false discovery rate

Published
2022

7. Host and gut microbial tryptophan metabolism and type 2 diabetes: an integrative analysis of host genetics, diet, gut microbiome and circulating metabolites in cohort studies

Author

Qi, Qibin, Li, Jun, Yu, Bing, Moon, Jee-Young, Chai, Jin C, Merino, Jordi, Hu, Jie, Ruiz-Canela, Miguel, Rebholz, Casey, Wang, Zheng, Usyk, Mykhaylo, Chen, Guo-Chong, Porneala, Bianca C, Wang, Wenshuang, Nguyen, Ngoc Quynh, Feofanova, Elena V, Grove, Megan L, Wang, Thomas J, Gerszten, Robert E, Dupuis, Josée, Salas-Salvadó, Jordi, Bao, Wei, Perkins, David L, Daviglus, Martha L, Thyagarajan, Bharat, Cai, Jianwen, Wang, Tao, Manson, JoAnn E, Martínez-González, Miguel A, Selvin, Elizabeth, Rexrode, Kathryn M, Clish, Clary B, Hu, Frank B, Meigs, James B, Knight, Rob, Burk, Robert D, Boerwinkle, Eric, and Kaplan, Robert C

Subjects
Obesity, Human Genome, Prevention, Genetics, Nutrition, Diabetes, 2.2 Factors relating to the physical environment, Aetiology, Metabolic and endocrine, Oral and gastrointestinal, Bacteria, Cohort Studies, Diabetes Mellitus, Type 2, Diet, Gastrointestinal Microbiome, Humans, Kynurenine, Lactase, Tryptophan, diabetes mellitus, dietary factors, genetics, Clinical Sciences, Paediatrics and Reproductive Medicine, Gastroenterology & Hepatology
Abstract

ObjectiveTryptophan can be catabolised to various metabolites through host kynurenine and microbial indole pathways. We aimed to examine relationships of host and microbial tryptophan metabolites with incident type 2 diabetes (T2D), host genetics, diet and gut microbiota.MethodWe analysed associations between circulating levels of 11 tryptophan metabolites and incident T2D in 9180 participants of diverse racial/ethnic backgrounds from five cohorts. We examined host genome-wide variants, dietary intake and gut microbiome associated with these metabolites.ResultsTryptophan, four kynurenine-pathway metabolites (kynurenine, kynurenate, xanthurenate and quinolinate) and indolelactate were positively associated with T2D risk, while indolepropionate was inversely associated with T2D risk. We identified multiple host genetic variants, dietary factors, gut bacteria and their potential interplay associated with these T2D-relaetd metabolites. Intakes of fibre-rich foods, but not protein/tryptophan-rich foods, were the dietary factors most strongly associated with tryptophan metabolites. The fibre-indolepropionate association was partially explained by indolepropionate-associated gut bacteria, mostly fibre-using Firmicutes. We identified a novel association between a host functional LCT variant (determining lactase persistence) and serum indolepropionate, which might be related to a host gene-diet interaction on gut Bifidobacterium, a probiotic bacterium significantly associated with indolepropionate independent of other fibre-related bacteria. Higher milk intake was associated with higher levels of gut Bifidobacterium and serum indolepropionate only among genetically lactase non-persistent individuals.ConclusionHigher milk intake among lactase non-persistent individuals, and higher fibre intake were associated with a favourable profile of circulating tryptophan metabolites for T2D, potentially through the host-microbial cross-talk shifting tryptophan metabolism toward gut microbial indolepropionate production.

Published
2022

9. Plasma metabolomic profiles associated with mortality and longevity in a prospective analysis of 13,512 individuals

Author

Wang, Fenglei, Tessier, Anne-Julie, Liang, Liming, Wittenbecher, Clemens, Haslam, Danielle E., Fernández-Duval, Gonzalo, Heather Eliassen, A., Rexrode, Kathryn M., Tobias, Deirdre K., Li, Jun, Zeleznik, Oana, Grodstein, Francine, Martínez-González, Miguel A., Salas-Salvadó, Jordi, Clish, Clary, Lee, Kyu Ha, Sun, Qi, Stampfer, Meir J., Hu, Frank B., and Guasch-Ferré, Marta

Published
2023
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12. Plasma metabolites of a healthy lifestyle in relation to mortality and longevity: Four prospective US cohort studies

Author

Tessier, Anne-Julie, Wang, Fenglei, Liang, Liming, Wittenbecher, Clemens, Haslam, Danielle E., Eliassen, A. Heather, Tobias, Deirdre K., Li, Jun, Zeleznik, Oana A., Ascherio, Alberto, Sun, Qi, Stampfer, Meir J., Grodstein, Francine, Rexrode, Kathryn M., Manson, JoAnn E., Balasubramanian, Raji, Clish, Clary B., Martínez-González, Miguel A., Chavarro, Jorge E., Hu, Frank B., and Guasch-Ferré, Marta

Published
2024
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13. Association between Noise and Cardiovascular Disease in a Nationwide U.S. Prospective Cohort Study of Women Followed from 1988 to 2018

Author

Roscoe, Charlotte, Grady, Stephanie T., Hart, Jaime E., Iyer, Hari S., Munson, Jo Ann E., Rexrode, Kathryn M., Rimm, Eric B., Laden, Francine, and James, Peter

Subjects
Coronary heart disease -- Risk factors, Noise control -- Analysis, Mediation -- Analysis, Geospatial data -- Analysis, Air pollution -- Analysis, Sleep -- Analysis, Environmental issues, Health
Abstract

BACKGROUND: Long-term noise exposure is associated with cardiovascular disease (CVD), including acute cardiovascular events such as myocardial infarction and stroke. However, longitudinal cohort studies in the U.S. of long- term noise and CVD are almost exclusively from Europe and few modeled nighttime noise, when an individual is likely at home or asleep, separately from daytime noise. We aimed to examine the prospective association of outdoor long-term nighttime and daytime noise from anthropogenic sources with incident CVD using a U.S.-based, nationwide cohort of women. METHODS: We linked [L.sub.50] nighttime and [L.sub.50] daytime anthropogenic modeled noise estimates from a U.S. National Parks Service model ([L.sub.50]: sound pressure levels exceeded 50 percent of the time) to geocoded residential addresses of 114,116 participants in the Nurses' Health Study. We used time-varying Cox proportional hazards models to estimate risk of incident CVD, coronary heart disease (CHD), and stroke associated with long-term average (14-y measurement period) noise exposure, adjusted for potential individual- and area-level confounders and CVD risk factors (1988- 2018; biennial residential address updates; monthly CVD updates). We assessed effect modification by population density, region, air pollution, vegetation cover, and neighborhood socioeconomic status, and explored mediation by self-reported average nightly sleep duration. RESULTS: Over 2,548,927 person-years, there were 10,331 incident CVD events. In fully adjusted models, the hazard ratios for each interquartile range increase in [L.sub.50] nighttime noise (3.67 dBA) and [L.sub.50] daytime noise (4.35 dBA), respectively, were 1.04 (95% CI: 1.02, 1.06) and 1.04 (95% CI: 1.02, 1.07). Associations for total energy-equivalent noise level ([L.sub.eq]) measures were stronger than for the anthropogenic statistical [L.sub.50] noise measures. Similar associations were observed for CHD and stroke. Interaction analyses suggested that associations of [L.sub.50] nighttime and [L.sub.50] daytime noise with CVD did not differ by prespecified effect modifiers. We found no evidence that inadequate sleep ( DISCUSSION: Outdoor [L.sub.50] anthropogenic nighttime and daytime noise at the residential address was associated with a small increase in CVD risk in a cohort of adult female nurses. https://doi.org/10.1289/EHP12906, Introduction Noise, or unwanted sound exposure, is the second largest environmental cause of health problems, after air pollution, and has been associated with multiple adverse outcomes, such as annoyance, sleep [...]

Published
2023
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19. Metabolome-wide Association Study with Habitual Physical Activity in Four Prospective Cohort Studies

Author

Ding, Ming, Zeleznik, Oana A, Guasch-Ferre, Marta, Hu, Jie, Lasky-Su, Jessica, Lee, I-Min, Jackson, Rebecca D, Shadyab, Aladdin H, LaMonte, Michael J, Clish, Clary, Eliassen, A Heather, Sacks, Frank, Willett, Walter C, Hu, Frank B, Rexrode, Kathryn M, and Kraft, Peter

Subjects
Public Health, Health Sciences, Clinical Research, Adult, Case-Control Studies, Exercise, Female, Humans, Lipid Metabolism, Metabolome, Middle Aged, Molecular Epidemiology, cohort studies, metabolomics, physical activity, Mathematical Sciences, Medical and Health Sciences, Epidemiology
Abstract

We identified plasma metabolites associated with habitual physical activity among 5,197 US participants from the Nurses' Health Study (NHS), Nurses' Health Study II (NHS II), and the Health Professionals Follow-up Study (HPFS). Physical activity was assessed every 2-4 years via self-report questionnaires. Blood was collected in the NHS in 1989-1990, in NHS II during 1996-1999, and in the HPFS during 1993-1995. Metabolic profiling was conducted by liquid chromatography-mass spectrometry. Our study included 337 known metabolites, with 256 of them classified as lipids. We corrected for multiple testing by controlling the tail probability of the proportion of false positives (TPPFP) and accounted for correlated tests using bootstrapping. Physical activity was significantly associated with 20 metabolites after correction for multiple testing (TPPFP < 0.05), and positive associations were found for most of the metabolites, including 2 amino acids (citrulline and glycine), 4 cholesteryl esters (C18:2, C18:1, C16:0, C18:3), 8 phosphocholines (PCs) (C36:4 PC-A, C34:3 PC plasmalogen, C36:3 PC plasmalogen, C34:2 PC plasmalogen, C36:2 PC) and lysophosphatidylcholines (C18:2, C20:5, C18:1), and 3 phosphatidylethanolamines (PEs) (C38:3 PE plasmalogen) and lysophosphatidylethanolamines (C18:2, C18:1). We independently replicated the 20 metabolites among 2,305 women in the Women's Health Initiative using 1993 data, and half of the metabolites were replicated. Our study may help identify biomarkers of physical activity and provide insight into biological mechanisms underlying the beneficial effect of being physically active on cardiometabolic health.

Published
2019

20. Multi‐phenotype analyses of hemostatic traits with cardiovascular events reveal novel genetic associations

Author

Temprano‐Sagrera, Gerard, Sitlani, Colleen M., Bone, William P., Martin‐Bornez, Miguel, Voight, Benjamin F., Morrison, Alanna C., Damrauer, Scott M., de Vries, Paul S., Smith, Nicholas L., Sabater‐Lleal, Maria, Dehghan, Abbas, Heath, Adam S, Morrison, Alanna C, Reiner, Alex P, Johnson, Andrew, Richmond, Anne, Peters, Annette, van Hylckama Vlieg, Astrid, McKnight, Barbara, Psaty, Bruce M, Hayward, Caroline, Ward‐Caviness, Cavin, O’Donnell, Christopher, Chasman, Daniel, Strachan, David P, Tregouet, David A, Mook‐Kanamori, Dennis, Gill, Dipender, Thibord, Florian, Asselbergs, Folkert W, Leebeek, Frank W.G., Rosendaal, Frits R, Davies, Gail, Homuth, Georg, Temprano, Gerard, Campbell, Harry, Taylor, Herman A, Bressler, Jan, Huffman, Jennifer E, Rotter, Jerome I, Yao, Jie, Wilson, James F, Bis, Joshua C, Hahn, Julie M, Desch, Karl C, Wiggins, Kerri L, Raffield, Laura M, Bielak, Lawrence F, Yanek, Lisa R, Kleber, Marcus E, Mueller, Martina, Kavousi, Maryam, Mangino, Massimo, Liu, Melissa, Brown, Michael R, Conomos, Matthew P, Jhun, Min‐A, Chen, Ming‐Huei, de Maat, Moniek P.M., Pankratz, Nathan, Smith, Nicholas L, Peyser, Patricia A, Elliot, Paul, de Vries, Paul S, Wei, Peng, Wild, Philipp S, Morange, Pierre E, van der Harst, Pim, Yang, Qiong, Le, Ngoc‐Quynh, Marioni, Riccardo, Li, Ruifang, Damrauer, Scott M, Cox, Simon R, Trompet, Stella, Felix, Stephan B, Völker, Uwe, Tang, Weihong, Koenig, Wolfgang, Jukema, J. Wouter, Guo, Xiuqing, Lindstrom, Sara, Wang, Lu, Smith, Erin N, Gordon, William, de Andrade, Mariza, Brody, Jennifer A, Pattee, Jack W, Haessler, Jeffrey, Brumpton, Ben M, Chasman, Daniel I, Suchon, Pierre, Turman, Constance, Germain, Marine, MacDonald, James, Braekkan, Sigrid K, Armasu, Sebastian M, Jackson, Rabecca D, Nielsen, Jonas B, Giulianini, Franco, Puurunen, Marja K, Ibrahim, Manal, Heckbert, Susan R, Bammler, Theo K, Frazer, Kelly A, McCauley, Bryan M, Taylor, Kent, Pankow, James S, Reiner, Alexander P, Gabrielsen, Maiken E, Deleuze, Jean‐François, O’Donnell, Chris J, Kim, Jihye, Kraft, Peter, Hansen, John‐Bjarne, Heit, John A, Kooperberg, Charles, Hveem, Kristian, Ridker, Paul M, Morange, Pierre‐Emmanuel, Johnson, Andrew D, Kabrhel, Christopher, Trégouët, David‐Alexandre, Malik, Rainer, Chauhan, Ganesh, Traylor, Matthew, Sargurupremraj, Muralidharan, Okada, Yukinori, Mishra, Aniket, Rutten‐Jacobs, Loes, Giese, Anne‐Katrin, van der Laan, Sander W, Gretarsdottir, Solveig, Anderson, Christopher D, Chong, Michael, Adams, Hieab HH, Ago, Tetsuro, Almgren, Peter, Amouyel, Philippe, Ay, Hakan, Bartz, Traci M, Benavente, Oscar R, Bevan, Steve, Boncoraglio, Giorgio B, Brown, Robert D, Butterworth, Adam S, Carrera, Caty, Carty, Cara L, Chen, Wei‐Min, Cole, John W, Correa, Adolfo, Cotlarciuc, Ioana, Cruchaga, Carlos, Danesh, John, de Bakker, Paul IW, DeStefano, Anita L, den Hoed, Marcel, Duan, Qing, Engelter, Stefan T, Falcone, Guido J, Gottesman, Rebecca F, Grewal, Raji P, Gudnason, Vilmundur, Gustafsson, Stefan, Harris, Tamara B, Hassan, Ahamad, Havulinna, Aki S, Holliday, Elizabeth G, Howard, George, Hsu, Fang‐Chi, Hyacinth, Hyacinth I, Arfan Ikram, M, Ingelsson, Erik, Irvin, Marguerite R, Jian, Xueqiu, Jiménez‐Conde, Jordi, Johnson, Julie A, Jukema, J Wouter, Kanai, Masahiro, Keene, Keith L, Kissela, Brett M, Kleindorfer, Dawn O, Kubo, Michiaki, Lange, Leslie A, Langefeld, Carl D, Langenberg, Claudia, Launer, Lenore J, Lee, Jin‐Moo, Lemmens, Robin, Leys, Didier, Lewis, Cathryn M, Lin, Wei‐Yu, Lindgren, Arne G, Lorentzen, Erik, Magnusson, Patrik K, Maguire, Jane, Manichaikul, Ani, McArdle, Patrick F, Meschia, James F, Mitchell, Braxton D, Mosley, Thomas H, Nalls, Michael A, Ninomiya, Toshiharu, O’Donnell, Martin J, Pulit, Sara L, Rannikmäe, Kristiina, Rexrode, Kathryn M, Rice, Kenneth, Rich, Stephen S, Rost, Natalia S, Rothwell, Peter M, Rundek, Tatjana, Sacco, Ralph L, Sakaue, Saori, Sale, Michele M, Salomaa, Veikko, Sapkota, Bishwa R, Schmidt, Reinhold, Schmidt, Carsten O, Schminke, Ulf, Sharma, Pankaj, Slowik, Agnieszka, Sudlow, Cathie LM, Tanislav, Christian, Tatlisumak, Turgut, Taylor, Kent D, Thijs, Vincent NS, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tiedt, Steffen, Tzourio, Christophe, van Duijn, Cornelia M, Walters, Matthew, Wareham, Nicholas J, Wassertheil‐Smoller, Sylvia, Wilson, James G, Yusuf, Salim, Amin, Najaf, Aparicio, Hugo S, Arnett, Donna K, Attia, John, Beiser, Alexa S, Berr, Claudine, Buring, Julie E, Bustamante, Mariana, Caso, Valeria, Cheng, Yu‐Ching, Hoan Choi, Seung, Chowhan, Ayesha, Cullell, Natalia, Dartigues, Jean‐François, Delavaran, Hossein, Delgado, Pilar, Dörr, Marcus, Engström, Gunnar, Ford, Ian, Gurpreet, Wander S, Hamsten, Anders, Heitsch, Laura, Hozawa, Atsushi, Ibanez, Laura, Ilinca, Andreea, Ingelsson, Martin, Iwasaki, Motoki, Jackson, Rebecca D, Jood, Katarina, Jousilahti, Pekka, Kaffashian, Sara, Kalra, Lalit, Kamouchi, Masahiro, Kitazono, Takanari, Kjartansson, Olafur, Kloss, Manja, Koudstaal, Peter J, Krupinski, Jerzy, Labovitz, Daniel L, Laurie, Cathy C, Levi, Christopher R, Li, Linxin, Lind, Lars, Lindgren, Cecilia M, Lioutas, Vasileios, Mei Liu, Yong, Lopez, Oscar L, Makoto, Hirata, Martinez‐Majander, Nicolas, Matsuda, Koichi, Minegishi, Naoko, Montaner, Joan, Morris, Andrew P, Muiño, Elena, Müller‐Nurasyid, Martina, Norrving, Bo, Ogishima, Soichi, Parati, Eugenio A, Reddy Peddareddygari, Leema, Pedersen, Nancy L, Pera, Joanna, Perola, Markus, Pezzini, Alessandro, Pileggi, Silvana, Rabionet, Raquel, Riba‐Llena, Iolanda, Ribasés, Marta, Romero, Jose R, Roquer, Jaume, Rudd, Anthony G, Sarin, Antti‐Pekka, Sarju, Ralhan, Sarnowski, Chloe, Sasaki, Makoto, Satizabal, Claudia L, Satoh, Mamoru, Sattar, Naveed, Sawada, Norie, Sibolt, Gerli, Sigurdsson, Ásgeir, Smith, Albert, Sobue, Kenji, Soriano‐Tárraga, Carolina, Stanne, Tara, Colin Stine, O, Stott, David J, Strauch, Konstantin, Takai, Takako, Tanaka, Hideo, Tanno, Kozo, Teumer, Alexander, Tomppo, Liisa, Torres‐Aguila, Nuria P, Touze, Emmanuel, Tsugane, Shoichiro, Uitterlinden, Andre G, Valdimarsson, Einar M, van der Lee, Sven J, Völzke, Henry, Wakai, Kenji, Weir, David, Williams, Stephen R, Wolfe, Charles DA, Wong, Quenna, Xu, Huichun, Yamaji, Taiki, Sanghera, Dharambir K, Melander, Olle, Jern, Christina, Strbian, Daniel, Fernandez‐Cadenas, Israel, Longstreth, W T, Rolfs, Arndt, Hata, Jun, Woo, Daniel, Rosand, Jonathan, Pare, Guillaume, Hopewell, Jemma C, Saleheen, Danish, Stefansson, Kari, Worrall, Bradford B, Kittner, Steven J, Seshadri, Sudha, Fornage, Myriam, Markus, Hugh S, Howson, Joanna MM, Kamatani, Yoichiro, Debette, Stephanie, and Dichgans, Martin

Published
2022
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23. Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes

Author

Malik, Rainer, Chauhan, Ganesh, Traylor, Matthew, Sargurupremraj, Muralidharan, Okada, Yukinori, Mishra, Aniket, Rutten-Jacobs, Loes, Giese, Anne-Katrin, van der Laan, Sander W, Gretarsdottir, Solveig, Anderson, Christopher D, Chong, Michael, Adams, Hieab HH, Ago, Tetsuro, Almgren, Peter, Amouyel, Philippe, Ay, Hakan, Bartz, Traci M, Benavente, Oscar R, Bevan, Steve, Boncoraglio, Giorgio B, Brown, Robert D, Butterworth, Adam S, Carrera, Caty, Carty, Cara L, Chasman, Daniel I, Chen, Wei-Min, Cole, John W, Correa, Adolfo, Cotlarciuc, Ioana, Cruchaga, Carlos, Danesh, John, de Bakker, Paul IW, DeStefano, Anita L, den Hoed, Marcel, Duan, Qing, Engelter, Stefan T, Falcone, Guido J, Gottesman, Rebecca F, Grewal, Raji P, Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeffrey, Harris, Tamara B, Hassan, Ahamad, Havulinna, Aki S, Heckbert, Susan R, Holliday, Elizabeth G, Howard, George, Hsu, Fang-Chi, Hyacinth, Hyacinth I, Ikram, M Arfan, Ingelsson, Erik, Irvin, Marguerite R, Jian, Xueqiu, Jiménez-Conde, Jordi, Johnson, Julie A, Jukema, J Wouter, Kanai, Masahiro, Keene, Keith L, Kissela, Brett M, Kleindorfer, Dawn O, Kooperberg, Charles, Kubo, Michiaki, Lange, Leslie A, Langefeld, Carl D, Langenberg, Claudia, Launer, Lenore J, Lee, Jin-Moo, Lemmens, Robin, Leys, Didier, Lewis, Cathryn M, Lin, Wei-Yu, Lindgren, Arne G, Lorentzen, Erik, Magnusson, Patrik K, Maguire, Jane, Manichaikul, Ani, McArdle, Patrick F, Meschia, James F, Mitchell, Braxton D, Mosley, Thomas H, Nalls, Michael A, Ninomiya, Toshiharu, O’Donnell, Martin J, Psaty, Bruce M, Pulit, Sara L, Rannikmäe, Kristiina, Reiner, Alexander P, Rexrode, Kathryn M, Rice, Kenneth, Rich, Stephen S, Ridker, Paul M, Rost, Natalia S, Rothwell, Peter M, Rotter, Jerome I, Rundek, Tatjana, Sacco, Ralph L, Sakaue, Saori, and Sale, Michele M

Subjects
Biological Sciences, Genetics, Human Genome, Stroke, Clinical Research, Brain Disorders, Aetiology, 2.1 Biological and endogenous factors, Cardiovascular, Computational Biology, Databases, Genetic, Epigenesis, Genetic, Female, Gene Regulatory Networks, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, INDEL Mutation, Linkage Disequilibrium, Male, Models, Genetic, Polymorphism, Single Nucleotide, Risk Factors, AFGen Consortium, Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, International Genomics of Blood Pressure (iGEN-BP) Consortium, INVENT Consortium, STARNET, BioBank Japan Cooperative Hospital Group, COMPASS Consortium, EPIC-CVD Consortium, EPIC-InterAct Consortium, International Stroke Genetics Consortium, METASTROKE Consortium, Neurology Working Group of the CHARGE Consortium, NINDS Stroke Genetics Network, UK Young Lacunar DNA Study, MEGASTROKE Consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Stroke has multiple etiologies, but the underlying genes and pathways are largely unknown. We conducted a multiancestry genome-wide-association meta-analysis in 521,612 individuals (67,162 cases and 454,450 controls) and discovered 22 new stroke risk loci, bringing the total to 32. We further found shared genetic variation with related vascular traits, including blood pressure, cardiac traits, and venous thromboembolism, at individual loci (n = 18), and using genetic risk scores and linkage-disequilibrium-score regression. Several loci exhibited distinct association and pleiotropy patterns for etiological stroke subtypes. Eleven new susceptibility loci indicate mechanisms not previously implicated in stroke pathophysiology, with prioritization of risk variants and genes accomplished through bioinformatics analyses using extensive functional datasets. Stroke risk loci were significantly enriched in drug targets for antithrombotic therapy.

Published
2018

27. Analysis of potential protein-modifying variants in 9000 endometriosis patients and 150000 controls of European ancestry.

Author

Sapkota, Yadav, Vivo, Immaculata De, Steinthorsdottir, Valgerdur, Fassbender, Amelie, Bowdler, Lisa, Buring, Julie E, Edwards, Todd L, Jones, Sarah, O, Dorien, Peterse, Daniëlle, Rexrode, Kathryn M, Ridker, Paul M, Schork, Andrew J, Thorleifsson, Gudmar, Wallace, Leanne M, iPSYCH-SSI-Broad Group, Kraft, Peter, Morris, Andrew P, Nyholt, Dale R, Edwards, Digna R Velez, Nyegaard, Mette, D'Hooghe, Thomas, Chasman, Daniel I, Stefansson, Kari, Missmer, Stacey A, and Montgomery, Grant W

Subjects
iPSYCH-SSI-Broad Group, Humans, Endometriosis, Genetic Predisposition to Disease, Case-Control Studies, Chromosome Mapping, Polymorphism, Single Nucleotide, European Continental Ancestry Group, Female, Meta-Analysis as Topic, Genetic Variation, Genome-Wide Association Study, Exome, Biomarkers, Whole Exome Sequencing, Genetics, Human Genome, Clinical Research, 2.1 Biological and endogenous factors
Abstract

Genome-wide association (GWA) studies have identified 19 independent common risk loci for endometriosis. Most of the GWA variants are non-coding and the genes responsible for the association signals have not been identified. Herein, we aimed to assess the potential role of protein-modifying variants in endometriosis using exome-array genotyping in 7164 cases and 21005 controls, and a replication set of 1840 cases and 129016 controls of European ancestry. Results in the discovery sample identified significant evidence for association with coding variants in single-variant (rs1801232-CUBN) and gene-level (CIITA and PARP4) meta-analyses, but these did not survive replication. In the combined analysis, there was genome-wide significant evidence for rs13394619 (P = 2.3 × 10-9) in GREB1 at 2p25.1 - a locus previously identified in a GWA meta-analysis of European and Japanese samples. Despite sufficient power, our results did not identify any protein-modifying variants (MAF > 0.01) with moderate or large effect sizes in endometriosis, although these variants may exist in non-European populations or in high-risk families. The results suggest continued discovery efforts should focus on genotyping large numbers of surgically-confirmed endometriosis cases and controls, and/or sequencing high-risk families to identify novel rare variants to provide greater insights into the molecular pathogenesis of the disease.

Published
2017

28. Detection of genetic loci associated with plasma fetuin-A: a meta-analysis of genome-wide association studies from the CHARGE Consortium

Author

Jensen, Majken K, Jensen, Richard A, Mukamal, Kenneth J, Guo, Xiuqing, Yao, Jie, Sun, Qi, Cornelis, Marilyn, Liu, Yongmei, Chen, Ming-Huei, Kizer, Jorge R, Djoussé, Luc, Siscovick, David S, Psaty, Bruce M, Zmuda, Joseph M, Rotter, Jerome I, Garcia, Melissa, Harris, Tamara, Chen, Ida, Goodarzi, Mark O, Nalls, Michael A, Keller, Margaux, Arnold, Alice M, Newman, Anne B, Hoogeveen, Ron C, Rexrode, Kathryn M, Rimm, Eric B, Hu, Frank B, Ramachandran, Vasan S, Katz, Ronit, Pankow, James S, and Ix, Joachim H

Subjects
Human Genome, Genetics, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Adult, Black or African American, Aged, Diabetes Mellitus, Type 2, Female, Genetic Loci, Genome-Wide Association Study, Genotype, Humans, Male, Metabolic Syndrome, Middle Aged, Polymorphism, Single Nucleotide, White People, alpha-2-HS-Glycoprotein, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Plasma fetuin-A is associated with type 2 diabetes, and AHSG, the gene encoding fetuin-A, has been identified as a susceptibility locus for diabetes and metabolic syndrome. Thus far, unbiased investigations of the genetic determinants of plasma fetuin-A concentrations have not been conducted. We searched for single nucleotide polymorphisms (SNPs) related to fetuin-A concentrations by a genome-wide association study in six population-based studies. We examined the association of fetuin-A levels with ∼ 2.5 million genotyped and imputed SNPs in 9,055 participants of European descent and 2,119 African Americans. In both ethnicities, the strongest associations were centered in a region with a high degree of LD near the AHSG locus. Among 136 genome-wide significant (P

Published
2017

29. Meta-analysis identifies five novel loci associated with endometriosis highlighting key genes involved in hormone metabolism.

Author

Sapkota, Yadav, Steinthorsdottir, Valgerdur, Morris, Andrew P, Fassbender, Amelie, Rahmioglu, Nilufer, De Vivo, Immaculata, Buring, Julie E, Zhang, Futao, Edwards, Todd L, Jones, Sarah, O, Dorien, Peterse, Daniëlle, Rexrode, Kathryn M, Ridker, Paul M, Schork, Andrew J, MacGregor, Stuart, Martin, Nicholas G, Becker, Christian M, Adachi, Sosuke, Yoshihara, Kosuke, Enomoto, Takayuki, Takahashi, Atsushi, Kamatani, Yoichiro, Matsuda, Koichi, Kubo, Michiaki, Thorleifsson, Gudmar, Geirsson, Reynir T, Thorsteinsdottir, Unnur, Wallace, Leanne M, iPSYCH-SSI-Broad Group, Yang, Jian, Velez Edwards, Digna R, Nyegaard, Mette, Low, Siew-Kee, Zondervan, Krina T, Missmer, Stacey A, D'Hooghe, Thomas, Montgomery, Grant W, Chasman, Daniel I, Stefansson, Kari, Tung, Joyce Y, and Nyholt, Dale R

Subjects
iPSYCH-SSI-Broad Group, Humans, Endometriosis, Genetic Predisposition to Disease, Gonadal Steroid Hormones, Estrogen Receptor alpha, Genotype, Polymorphism, Single Nucleotide, Adult, Aged, Middle Aged, Female, Metabolic Networks and Pathways, Genome-Wide Association Study, Genetic Loci, Genetics, Pain Research, Human Genome, Contraception/Reproduction, Clinical Research, Prevention, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning
Abstract

Endometriosis is a heritable hormone-dependent gynecological disorder, associated with severe pelvic pain and reduced fertility; however, its molecular mechanisms remain largely unknown. Here we perform a meta-analysis of 11 genome-wide association case-control data sets, totalling 17,045 endometriosis cases and 191,596 controls. In addition to replicating previously reported loci, we identify five novel loci significantly associated with endometriosis risk (P

Published
2017

33. Plasma metabolites of a healthy lifestyle in relation to mortality and longevity:Four prospective US cohort studies

Author

Tessier, Anne Julie, Wang, Fenglei, Liang, Liming, Wittenbecher, Clemens, Haslam, Danielle E., Eliassen, A. Heather, Tobias, Deirdre K., Li, Jun, Zeleznik, Oana A., Ascherio, Alberto, Sun, Qi, Stampfer, Meir J., Grodstein, Francine, Rexrode, Kathryn M., Manson, Jo Ann E., Balasubramanian, Raji, Clish, Clary B., Martínez-González, Miguel A., Chavarro, Jorge E., Hu, Frank B., Guasch-Ferré, Marta, Tessier, Anne Julie, Wang, Fenglei, Liang, Liming, Wittenbecher, Clemens, Haslam, Danielle E., Eliassen, A. Heather, Tobias, Deirdre K., Li, Jun, Zeleznik, Oana A., Ascherio, Alberto, Sun, Qi, Stampfer, Meir J., Grodstein, Francine, Rexrode, Kathryn M., Manson, Jo Ann E., Balasubramanian, Raji, Clish, Clary B., Martínez-González, Miguel A., Chavarro, Jorge E., Hu, Frank B., and Guasch-Ferré, Marta

Abstract

Background: A healthy lifestyle is associated with a lower premature mortality risk and with longer life expectancy. However, the metabolic pathways of a healthy lifestyle and how they relate to mortality and longevity are unclear. We aimed to identify and replicate a healthy lifestyle metabolomic signature and examine how it is related to total and cause-specific mortality risk and longevity. Methods: In four large cohorts with 13,056 individuals and 28-year follow-up, we assessed five healthy lifestyle factors, used liquid chromatography mass spectrometry to profile plasma metabolites, and ascertained deaths with death certificates. The unique healthy lifestyle metabolomic signature was identified using an elastic regression. Multivariable Cox regressions were used to assess associations of the signature with mortality and longevity. Findings: The identified healthy lifestyle metabolomic signature was reflective of lipid metabolism pathways. Shorter and more saturated triacylglycerol and diacylglycerol metabolite sets were inversely associated with the healthy lifestyle score, whereas cholesteryl ester and phosphatidylcholine plasmalogen sets were positively associated. Participants with a higher healthy lifestyle metabolomic signature had a 17% lower risk of all-cause mortality, 19% for cardiovascular disease mortality, and 17% for cancer mortality and were 25% more likely to reach longevity. The healthy lifestyle metabolomic signature explained 38% of the association between the self-reported healthy lifestyle score and total mortality risk and 49% of the association with longevity. Conclusions: This study identifies a metabolomic signature that measures adherence to a healthy lifestyle and shows prediction of total and cause-specific mortality and longevity. Funding: This work was funded by the NIH, CIHR, AHA, Novo Nordisk Foundation, and SciLifeLab.

Published
2024

37. Mixtures of Urinary Phenol and Phthalate Metabolite Concentrations in Relation to Serum Lipid Levels among Pregnant Women: Results from the EARTH Study.

Author

Shen, Xilin, Génard-Walton, Maximilien, Williams, Paige L., James-Todd, Tamarra, Ford, Jennifer B., Rexrode, Kathryn M., Calafat, Antonia M., Zhang, Dan, Chavarro, Jorge E., Hauser, Russ, and Mínguez-Alarcón, Lidia

Subjects
BLOOD lipids, LDL cholesterol, HIGH density lipoproteins, ENDOCRINE disruptors, PREGNANT women, PARABENS
Abstract

We examined whether mixtures of urinary concentrations of bisphenol A (BPA), parabens and phthalate metabolites were associated with serum lipid levels among 175 pregnant women who enrolled in the Environment and Reproductive Health (EARTH) Study (2005–2017), including triglycerides, total cholesterol, high-density lipoprotein (HDL), non-HDL, and low-density lipoprotein (LDL). We applied Bayesian Kernel Machine Regression (BKMR) and quantile g-computation while adjusting for confounders. In the BKMR models, we found no associations between chemical mixture and lipid levels, e.g., total cholesterol [mean difference (95% CRI, credible interval) = 0.02 (−0.31, 0.34)] and LDL [mean difference (95% CRI) = 0.10 (−0.22, 0.43)], when comparing concentrations at the 75th to the 25th percentile. When stratified by BMI, we found suggestive positive relationships between urinary propylparaben and total cholesterol and LDL among women with high BMI [mean difference (95% CRI) = 0.25 (−0.26, 0.75) and 0.35 (−0.25, 0.95)], but not with low BMI [mean difference (95% CRI) = 0.00 (−0.06, 0.07) and 0.00 (−0.07, 0.07)]. No association was found by quantile g-computation. This exploratory study suggests mixtures of phenol and phthalate metabolites were not associated with serum lipid levels during pregnancy, while there were some suggestive associations for certain BMI subgroups. Larger longitudinal studies with multiple assessments of both exposure and outcome are needed to corroborate these novel findings. [ABSTRACT FROM AUTHOR]

Published
2024
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38. Assault-related anoxia and neck injuries in US emergency departments.

Author

Khurana, Bharti, Prakash, Jaya, Lewis O'Connor, Annie, Green, William, Rexrode, Kathryn M., and Loder, Randall T.

Subjects
NECK injuries, WOUNDS & injuries, INTIMATE partner violence, RESEARCH funding, CRIMINALS, SPOUSES, HOSPITAL emergency services, RETROSPECTIVE studies, DESCRIPTIVE statistics, ASPHYXIA, EPIDEMIOLOGY, MEDICAL screening, ASSAULT & battery, HYPOXEMIA, DISEASE risk factors, DISEASE complications
Published
2024
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39. A Plasma Metabolite Score Related to Psychological Distress and Diabetes Risk: A Nested Case-control Study in US Women.

Author

Huang, Tianyi, Zhu, Yiwen, Shutta, Katherine H, Balasubramanian, Raji, Zeleznik, Oana A, Rexrode, Kathryn M, Clish, Clary B, Sun, Qi, Hu, Frank B, Kubzansky, Laura D, and Hankinson, Susan E

Subjects
PSYCHOLOGICAL distress, PSILOCYBIN, DIABETES, GESTATIONAL diabetes, CASE-control method, BODY mass index, HEALTH behavior
Abstract

Context Psychological distress has been linked to diabetes risk. Few population-based, epidemiologic studies have investigated the potential molecular mechanisms (eg, metabolic dysregulation) underlying this association. Objective To evaluate the association between a metabolomic signature for psychological distress and diabetes risk. Methods We conducted a nested case-control study of plasma metabolomics and diabetes risk in the Nurses' Health Study, including 728 women (mean age: 55.2 years) with incident diabetes and 728 matched controls. Blood samples were collected between 1989 and 1990 and incident diabetes was diagnosed between 1992 and 2008. Based on our prior work, we calculated a weighted plasma metabolite-based distress score (MDS) comprised of 19 metabolites. We used conditional logistic regression accounting for matching factors and other diabetes risk factors to estimate odds ratios (OR) and 95% confidence intervals (CI) for diabetes risk according to MDS. Results After adjusting for sociodemographic factors, family history of diabetes, and health behaviors, the OR (95% CI) for diabetes risk across quintiles of the MDS was 1.00 (reference) for Q1, 1.16 (0.77, 1.73) for Q2, 1.30 (0.88, 1.91) for Q3, 1.99 (1.36, 2.92) for Q4, and 2.47 (1.66, 3.67) for Q5. Each SD increase in MDS was associated with 36% higher diabetes risk (95% CI: 1.21, 1.54; P -trend <.0001). This association was moderately attenuated after additional adjustment for body mass index (comparable OR: 1.17; 95% CI: 1.02, 1.35; P -trend =.02). The MDS explained 17.6% of the association between self-reported psychological distress (defined as presence of depression or anxiety symptoms) and diabetes risk (P =.04). Conclusion MDS was significantly associated with diabetes risk in women. These results suggest that differences in multiple lipid and amino acid metabolites may underlie the observed association between psychological distress and diabetes risk. [ABSTRACT FROM AUTHOR]

Published
2024
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