Search

Your search keyword '"Huan, Tianxiao"' showing total 461 results
Start Over Author "Huan, Tianxiao"
461 results on '"Huan, Tianxiao"'

2. Circulating metabolites may illustrate relationship of alcohol consumption with cardiovascular disease

Author

Li, Yi, Wang, Mengyao, Liu, Xue, Rong, Jian, Miller, Patricia Emogene, Joehanes, Roby, Huan, Tianxiao, Guo, Xiuqing, Rotter, Jerome I, Smith, Jennifer A, Yu, Bing, Nayor, Matthew, Levy, Daniel, Liu, Chunyu, and Ma, Jiantao

Subjects
Biomedical and Clinical Sciences, Public Health, Health Sciences, Alcoholism, Alcohol Use and Health, Heart Disease - Coronary Heart Disease, Substance Misuse, Prevention, Cardiovascular, Aging, Heart Disease, Oral and gastrointestinal, Cancer, Stroke, Good Health and Well Being, Humans, Female, Middle Aged, Male, Cardiovascular Diseases, Prospective Studies, Alcohol Drinking, Coronary Disease, Diet, Risk Factors, Alcohol consumption, Cardiovascular disease, Metabolites, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundMetabolite signatures of long-term alcohol consumption are lacking. To better understand the molecular basis linking alcohol drinking and cardiovascular disease (CVD), we investigated circulating metabolites associated with long-term alcohol consumption and examined whether these metabolites were associated with incident CVD.MethodsCumulative average alcohol consumption (g/day) was derived from the total consumption of beer, wine, and liquor on average of 19 years in 2428 Framingham Heart Study Offspring participants (mean age 56 years, 52% women). We used linear mixed models to investigate the associations of alcohol consumption with 211 log-transformed plasma metabolites, adjusting for age, sex, batch, smoking, diet, physical activity, BMI, and familial relationship. Cox models were used to test the association of alcohol-related metabolite scores with fatal and nonfatal incident CVD (myocardial infarction, coronary heart disease, stroke, and heart failure).ResultsWe identified 60 metabolites associated with cumulative average alcohol consumption (p

Published
2023

3. Epigenome-wide DNA methylation association study of circulating IgE levels identifies novel targets for asthma.

Author

Recto, Kathryn, Kachroo, Priyadarshini, Huan, Tianxiao, Van Den Berg, David, Lee, Gha, Bui, Helena, Lee, Dong, Gereige, Jessica, Yao, Chen, Hwang, Shih-Jen, Joehanes, Roby, Weiss, Scott, OConnor, George, Levy, Daniel, and DeMeo, Dawn

Subjects
Asthma, DNA methylation, Drug targets, EWAS, IgE, Lung, Mendelian randomization, RNA-Sequencing, eQTM, Female, Humans, Child, Male, DNA Methylation, Epigenome, Genome-Wide Association Study, Asthma, Immunoglobulin E, Ubiquitin Thiolesterase
Abstract

BACKGROUND: Identifying novel epigenetic signatures associated with serum immunoglobulin E (IgE) may improve our understanding of molecular mechanisms underlying asthma and IgE-mediated diseases. METHODS: We performed an epigenome-wide association study using whole blood from Framingham Heart Study (FHS; n = 3,471, 46% females) participants and validated results using the Childhood Asthma Management Program (CAMP; n = 674, 39% females) and the Genetic Epidemiology of Asthma in Costa Rica Study (CRA; n = 787, 41% females). Using the closest gene to each IgE-associated CpG, we highlighted biologically plausible pathways underlying IgE regulation and analyzed the transcription patterns linked to IgE-associated CpGs (expression quantitative trait methylation loci; eQTMs). Using prior UK Biobank summary data from genome-wide association studies of asthma and allergy, we performed Mendelian randomization (MR) for causal inference testing using the IgE-associated CpGs from FHS with methylation quantitative trait loci (mQTLs) as instrumental variables. FINDINGS: We identified 490 statistically significant differentially methylated CpGs associated with IgE in FHS, of which 193 (39.3%) replicated in CAMP and CRA (FDR < 0.05). Gene ontology analysis revealed enrichment in pathways related to transcription factor binding, asthma, and other immunological processes. eQTM analysis identified 124 cis-eQTMs for 106 expressed genes (FDR < 0.05). MR in combination with drug-target analysis revealed CTSB and USP20 as putatively causal regulators of IgE levels (Bonferroni adjusted P

Published
2023

4. Multi-tissue epigenetic analysis identifies distinct associations underlying insulin resistance and Alzheimer’s disease at CPT1A locus

Author

Sarnowski, Chloé, Huan, Tianxiao, Ma, Yiyi, Joehanes, Roby, Beiser, Alexa, DeCarli, Charles S, Heard-Costa, Nancy L, Levy, Daniel, Lin, Honghuang, Liu, Ching-Ti, Liu, Chunyu, Meigs, James B, Satizabal, Claudia L, Florez, Jose C, Hivert, Marie-France, Dupuis, Josée, De Jager, Philip L, Bennett, David A, Seshadri, Sudha, and Morrison, Alanna C

Subjects
Biological Sciences, Genetics, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, Neurodegenerative, Alzheimer's Disease, Human Genome, Aging, Brain Disorders, Acquired Cognitive Impairment, Neurosciences, 2.1 Biological and endogenous factors, Aetiology, Metabolic and endocrine, Neurological, Humans, Alzheimer Disease, Diabetes Mellitus, Type 2, DNA Methylation, Epigenesis, Genetic, Genetic Markers, Genome-Wide Association Study, Insulin Resistance, Epigenetics, Insulin resistance, Alzheimer's disease, FHS, ROSMAP, DNA methylation, Alzheimer’s disease, Clinical Sciences, Paediatrics and Reproductive Medicine
Abstract

BackgroundInsulin resistance (IR) is a major risk factor for Alzheimer's disease (AD) dementia. The mechanisms by which IR predisposes to AD are not well-understood. Epigenetic studies may help identify molecular signatures of IR associated with AD, thus improving our understanding of the biological and regulatory mechanisms linking IR and AD.MethodsWe conducted an epigenome-wide association study of IR, quantified using the homeostatic model assessment of IR (HOMA-IR) and adjusted for body mass index, in 3,167 participants from the Framingham Heart Study (FHS) without type 2 diabetes at the time of blood draw used for methylation measurement. We identified DNA methylation markers associated with IR at the genome-wide level accounting for multiple testing (P

Published
2023

6. Epigenome-wide association study of mitochondrial genome copy number.

Author

Wang, Penglong, Castellani, Christina A, Yao, Jie, Huan, Tianxiao, Bielak, Lawrence F, Zhao, Wei, Haessler, Jeffrey, Joehanes, Roby, Sun, Xianbang, Guo, Xiuqing, Longchamps, Ryan J, Manson, JoAnn E, Grove, Megan L, Bressler, Jan, Taylor, Kent D, Lappalainen, Tuuli, Kasela, Silva, Van Den Berg, David J, Hou, Lifang, Reiner, Alexander, Liu, Yongmei, Boerwinkle, Eric, Smith, Jennifer A, Peyser, Patricia A, Fornage, Myriam, Rich, Stephen S, Rotter, Jerome I, Kooperberg, Charles, Arking, Dan E, Levy, Daniel, and Liu, Chunyu

Subjects
Heart Disease, Human Genome, Genetics, Cardiovascular, Generic health relevance, Aged, DNA Copy Number Variations, DNA Methylation, DNA, Mitochondrial, Epigenome, Female, Genome, Mitochondrial, Humans, Male, Middle Aged, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

We conducted cohort- and race-specific epigenome-wide association analyses of mitochondrial deoxyribonucleic acid (mtDNA) copy number (mtDNA CN) measured in whole blood from participants of African and European origins in five cohorts (n = 6182, mean age = 57-67 years, 65% women). In the meta-analysis of all the participants, we discovered 21 mtDNA CN-associated DNA methylation sites (CpG) (P

Published
2021

7. Expression quantitative trait methylation analysis elucidates gene regulatory effects of DNA methylation: the Framingham Heart Study

Author

Keshawarz, Amena, Bui, Helena, Joehanes, Roby, Ma, Jiantao, Liu, Chunyu, Huan, Tianxiao, Hwang, Shih-Jen, Tejada, Brandon, Sooda, Meera, Courchesne, Paul, Munson, Peter J., Demirkale, Cumhur Y., Yao, Chen, Heard-Costa, Nancy L., Pitsillides, Achilleas N., Lin, Honghuang, Liu, Ching-Ti, Wang, Yuxuan, Peloso, Gina M., Lundin, Jessica, Haessler, Jeffrey, Du, Zhaohui, Cho, Michael, Hersh, Craig P., Castaldi, Peter, Raffield, Laura M., Wen, Jia, Li, Yun, Reiner, Alexander P., Feolo, Mike, Sharopova, Nataliya, Vasan, Ramachandran S., DeMeo, Dawn L., Carson, April P., Kooperberg, Charles, and Levy, Daniel

Published
2023
Full Text
View/download PDF

8. Smoking, blood DNA methylation sites and lung cancer risk

Author

Domingo-Relloso, Arce, Joehanes, Roby, Rodriguez-Hernandez, Zulema, Lahousse, Lies, Haack, Karin, Fallin, M. Daniele, Herreros-Martinez, Miguel, Umans, Jason G., Best, Lyle G., Huan, Tianxiao, Liu, Chunyu, Ma, Jiantao, Yao, Chen, Jerolon, Allan, Bermudez, Jose D., Cole, Shelley A., Rhoades, Dorothy A., Levy, Daniel, Navas-Acien, Ana, and Tellez-Plaza, Maria

Published
2023
Full Text
View/download PDF

9. Epigenome-wide DNA methylation association study of circulating IgE levels identifies novel targets for asthma

Author

Abe, Namiko, Abecasis, Gonçalo, Aguet, Francois, Albert, Christine, Almasy, Laura, Alonso, Alvaro, Ament, Seth, Anderson, Peter, Anugu, Pramod, Applebaum-Bowden, Deborah, Ardlie, Kristin, Arking, Dan, Arnett, Donna K., Ashley-Koch, Allison, Aslibekyan, Stella, Assimes, Tim, Auer, Paul, Avramopoulos, Dimitrios, Ayas, Najib, Balasubramanian, Adithya, Barnard, John, Barnes, Kathleen, Barr, R. Graham, Barron-Casella, Emily, Barwick, Lucas, Beaty, Terri, Beck, Gerald, Becker, Diane, Becker, Lewis, Beer, Rebecca, Beitelshees, Amber, Benjamin, Emelia, Benos, Takis, Bezerra, Marcos, Bielak, Larry, Bis, Joshua, Blackwell, Thomas, Blangero, John, Blue, Nathan, Boerwinkle, Eric, Bowden, Donald W., Bowler, Russell, Brody, Jennifer, Broeckel, Ulrich, Broome, Jai, Brown, Deborah, Bunting, Karen, Burchard, Esteban, Bustamante, Carlos, Buth, Erin, Cade, Brian, Cardwell, Jonathan, Carey, Vincent, Carrier, Julie, Carson, April P., Carty, Cara, Casaburi, Richard, Casas Romero, Juan P., Casella, James, Castaldi, Peter, Chaffin, Mark, Chang, Christy, Chang, Yi-Cheng, Chasman, Daniel, Chavan, Sameer, Chen, Bo-Juen, Chen, Wei-Min, Ida Chen, Yii-Der, Cho, Michael, Choi, Seung Hoan, Chuang, Lee-Ming, Chung, Mina, Chung, Ren-Hua, Clish, Clary, Comhair, Suzy, Conomos, Matthew, Cornell, Elaine, Correa, Adolfo, Crandall, Carolyn, Crapo, James, Cupples, L. Adrienne, Curran, Joanne, Curtis, Jeffrey, Custer, Brian, Damcott, Coleen, Darbar, Dawood, David, Sean, Davis, Colleen, Daya, Michelle, de Andrade, Mariza, de las Fuentes, Lisa, de Vries, Paul, DeBaun, Michael, Deka, Ranjan, DeMeo, Dawn, Devine, Scott, Dinh, Huyen, Doddapaneni, Harsha, Duan, Qing, Dugan-Perez, Shannon, Duggirala, Ravi, Durda, Jon Peter, Dutcher, Susan K., Eaton, Charles, Ekunwe, Lynette, El Boueiz, Adel, Ellinor, Patrick, Emery, Leslie, Erzurum, Serpil, Farber, Charles, Farek, Jesse, Fingerlin, Tasha, Flickinger, Matthew, Fornage, Myriam, Franceschini, Nora, Frazar, Chris, Fu, Mao, Fullerton, Stephanie M., Fulton, Lucinda, Gabriel, Stacey, Gan, Weiniu, Gao, Shanshan, Gao, Yan, Gass, Margery, Geiger, Heather, Gelb, Bruce, Geraci, Mark, Germer, Soren, Gerszten, Robert, Ghosh, Auyon, Gibbs, Richard, Gignoux, Chris, Gladwin, Mark, Glahn, David, Gogarten, Stephanie, Gong, Da-Wei, Goring, Harald, Graw, Sharon, Gray, Kathryn J., Grine, Daniel, Gross, Colin, Gu, C. Charles, Guan, Yue, Guo, Xiuqing, Gupta, Namrata, Haessler, Jeff, Hall, Michael, Han, Yi, Hanly, Patrick, Harris, Daniel, Hawley, Nicola L., He, Jiang, Heavner, Ben, Heckbert, Susan, Hernandez, Ryan, Herrington, David, Hersh, Craig, Hidalgo, Bertha, Hixson, James, Hobbs, Brian, Hokanson, John, Hong, Elliott, Hoth, Karin, Hsiung, Chao (Agnes), Hu, Jianhong, Hung, Yi-Jen, Huston, Haley, Hwu, Chii Min, Irvin, Marguerite Ryan, Jackson, Rebecca, Jain, Deepti, Jaquish, Cashell, Johnsen, Jill, Johnson, Andrew, Johnson, Craig, Johnston, Rich, Jones, Kimberly, Kang, Hyun Min, Kaplan, Robert, Kardia, Sharon, Kelly, Shannon, Kenny, Eimear, Kessler, Michael, Khan, Alyna, Khan, Ziad, Kim, Wonji, Kimoff, John, Kinney, Greg, Konkle, Barbara, Kooperberg, Charles, Kramer, Holly, Lange, Christoph, Lange, Ethan, Lange, Leslie, Laurie, Cathy, Laurie, Cecelia, LeBoff, Meryl, Lee, Jiwon, Lee, Sandra, Lee, Wen-Jane, LeFaive, Jonathon, Levine, David, Levy, Daniel, Lewis, Joshua, Li, Xiaohui, Li, Yun, Lin, Henry, Lin, Honghuang, Lin, Xihong, Liu, Simin, Liu, Yongmei, Liu, Yu, Loos, Ruth J.F., Lubitz, Steven, Lunetta, Kathryn, Luo, James, Magalang, Ulysses, Mahaney, Michael, Make, Barry, Manichaikul, Ani, Manning, Alisa, Manson, JoAnn, Martin, Lisa, Marton, Melissa, Mathai, Susan, Mathias, Rasika, May, Susanne, McArdle, Patrick, McDonald, Merry-Lynn, McFarland, Sean, McGarvey, Stephen, McGoldrick, Daniel, McHugh, Caitlin, McNeil, Becky, Mei, Hao, Meigs, James, Menon, Vipin, Mestroni, Luisa, Metcalf, Ginger, Meyers, Deborah A., Mignot, Emmanuel, Mikulla, Julie, Min, Nancy, Minear, Mollie, Minster, Ryan L., Mitchell, Braxton D., Moll, Matt, Momin, Zeineen, Montasser, May E., Montgomery, Courtney, Muzny, Donna, Mychaleckyj, Josyf C., Nadkarni, Girish, Naik, Rakhi, Naseri, Take, Natarajan, Pradeep, Nekhai, Sergei, Nelson, Sarah C., Neltner, Bonnie, Nessner, Caitlin, Nickerson, Deborah, Nkechinyere, Osuji, North, Kari, O'Connell, Jeff, O'Connor, Tim, Ochs-Balcom, Heather, Okwuonu, Geoffrey, Pack, Allan, Paik, David T., Palmer, Nicholette, Pankow, James, Papanicolaou, George, Parker, Cora, Peloso, Gina, Peralta, Juan Manuel, Perez, Marco, Perry, James, Peters, Ulrike, Peyser, Patricia, Phillips, Lawrence S., Pleiness, Jacob, Pollin, Toni, Post, Wendy, Powers Becker, Julia, Preethi Boorgula, Meher, Preuss, Michael, Psaty, Bruce, Qasba, Pankaj, Qiao, Dandi, Qin, Zhaohui, Rafaels, Nicholas, Raffield, Laura, Rajendran, Mahitha, Ramachandran, Vasan S., Rao, D.C., Rasmussen-Torvik, Laura, Ratan, Aakrosh, Redline, Susan, Reed, Robert, Reeves, Catherine, Regan, Elizabeth, Reiner, Alex, Reupena, Muagututi‘a Sefuiva, Rice, Ken, Rich, Stephen, Robillard, Rebecca, Robine, Nicolas, Roden, Dan, Roselli, Carolina, Rotter, Jerome, Ruczinski, Ingo, Runnels, Alexi, Russell, Pamela, Ruuska, Sarah, Ryan, Kathleen, Sabino, Ester Cerdeira, Saleheen, Danish, Salimi, Shabnam, Salvi, Sejal, Salzberg, Steven, Sandow, Kevin, Sankaran, Vijay G., Santibanez, Jireh, Schwander, Karen, Schwartz, David, Sciurba, Frank, Seidman, Christine, Seidman, Jonathan, Sériès, Frédéric, Sheehan, Vivien, Sherman, Stephanie L., Shetty, Amol, Shetty, Aniket, Sheu, Wayne Hui-Heng, Shoemaker, M. Benjamin, Silver, Brian, Silverman, Edwin, Skomro, Robert, Smith, Albert Vernon, Smith, Jennifer, Smith, Josh, Smith, Nicholas, Smith, Tanja, Smoller, Sylvia, Snively, Beverly, Snyder, Michael, Sofer, Tamar, Sotoodehnia, Nona, Stilp, Adrienne M., Storm, Garrett, Streeten, Elizabeth, Su, Jessica Lasky, Sung, Yun Ju, Sylvia, Jody, Szpiro, Adam, Taliun, Daniel, Tang, Hua, Taub, Margaret, Taylor, Kent, Taylor, Matthew, Taylor, Simeon, Telen, Marilyn, Thornton, Timothy A., Threlkeld, Machiko, Tinker, Lesley, Tirschwell, David, Tishkoff, Sarah, Tiwari, Hemant, Tong, Catherine, Tracy, Russell, Tsai, Michael, Vaidya, Dhananjay, Van Den Berg, David, VandeHaar, Peter, Vrieze, Scott, Walker, Tarik, Wallace, Robert, Walts, Avram, Wang, Fei Fei, Wang, Heming, Wang, Jiongming, Watson, Karol, Watt, Jennifer, Weeks, Daniel E., Weinstock, Joshua, Weir, Bruce, Weiss, Scott T., Weng, Lu-Chen, Wessel, Jennifer, Willer, Cristen, Williams, Kayleen, Williams, L. Keoki, Williams, Scott, Wilson, Carla, Wilson, James, Winterkorn, Lara, Wong, Quenna, Wu, Baojun, Wu, Joseph, Xu, Huichun, Yanek, Lisa, Yang, Ivana, Yu, Ketian, Zekavat, Seyedeh Maryam, Zhang, Yingze, Zhao, Snow Xueyan, Zhao, Wei, Zhu, Xiaofeng, Ziv, Elad, Zody, Michael, Zoellner, Sebastian, Recto, Kathryn, Kachroo, Priyadarshini, Huan, Tianxiao, Lee, Gha Young, Bui, Helena, Lee, Dong Heon, Gereige, Jessica, Yao, Chen, Hwang, Shih-Jen, Joehanes, Roby, O’Connor, George T., and DeMeo, Dawn L.

Published
2023
Full Text
View/download PDF

15. Blood Leukocyte DNA Methylation Predicts Risk of Future Myocardial Infarction and Coronary Heart Disease

Author

Agha, Golareh, Mendelson, Michael M, Ward-Caviness, Cavin K, Joehanes, Roby, Huan, TianXiao, Gondalia, Rahul, Salfati, Elias, Brody, Jennifer A, Fiorito, Giovanni, Bressler, Jan, Chen, Brian H, Ligthart, Symen, Guarrera, Simonetta, Colicino, Elena, Just, Allan C, Wahl, Simone, Gieger, Christian, Vandiver, Amy R, Tanaka, Toshiko, Hernandez, Dena G, Pilling, Luke C, Singleton, Andrew B, Sacerdote, Carlotta, Krogh, Vittorio, Panico, Salvatore, Tumino, Rosario, Li, Yun, Zhang, Guosheng, Stewart, James D, Floyd, James S, Wiggins, Kerri L, Rotter, Jerome I, Multhaup, Michael, Bakulski, Kelly, Horvath, Steven, Tsao, Philip S, Absher, Devin M, Vokonas, Pantel, Hirschhorn, Joel, Fallin, M Daniele, Liu, Chunyu, Bandinelli, Stefania, Boerwinkle, Eric, Dehghan, Abbas, Schwartz, Joel D, Psaty, Bruce M, Feinberg, Andrew P, Hou, Lifang, Ferrucci, Luigi, Sotoodehnia, Nona, Matullo, Giuseppe, Peters, Annette, Fornage, Myriam, Assimes, Themistocles L, Whitsel, Eric A, Levy, Daniel, and Baccarelli, Andrea A

Subjects
Human Genome, Heart Disease, Clinical Research, Prevention, Heart Disease - Coronary Heart Disease, Atherosclerosis, Cardiovascular, Genetics, Adult, Aged, Cohort Studies, Coronary Disease, CpG Islands, DNA Methylation, Europe, Female, Genome-Wide Association Study, Humans, Incidence, Leukocytes, Male, Middle Aged, Myocardial Infarction, Population Groups, Prognosis, Prospective Studies, Risk, United States, coronary artery disease, coronary heart disease, epigenetics, genomics, gene expression regulation, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Public Health and Health Services, Cardiovascular System & Hematology
Abstract

BackgroundDNA methylation is implicated in coronary heart disease (CHD), but current evidence is based on small, cross-sectional studies. We examined blood DNA methylation in relation to incident CHD across multiple prospective cohorts.MethodsNine population-based cohorts from the United States and Europe profiled epigenome-wide blood leukocyte DNA methylation using the Illumina Infinium 450k microarray, and prospectively ascertained CHD events including coronary insufficiency/unstable angina, recognized myocardial infarction, coronary revascularization, and coronary death. Cohorts conducted race-specific analyses adjusted for age, sex, smoking, education, body mass index, blood cell type proportions, and technical variables. We conducted fixed-effect meta-analyses across cohorts.ResultsAmong 11 461 individuals (mean age 64 years, 67% women, 35% African American) free of CHD at baseline, 1895 developed CHD during a mean follow-up of 11.2 years. Methylation levels at 52 CpG (cytosine-phosphate-guanine) sites were associated with incident CHD or myocardial infarction (false discovery rate

Published
2019

16. Integrative Genomics Analysis Unravels Tissue-Specific Pathways, Networks, and Key Regulators of Blood Pressure Regulation

Author

Zhao, Yuqi, Blencowe, Montgomery, Shi, Xingyi, Shu, Le, Levian, Candace, Ahn, In Sook, Kim, Stuart K, Huan, Tianxiao, Levy, Daniel, and Yang, Xia

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Heart Disease, Cardiovascular, Genetics, Biotechnology, Human Genome, Hypertension, Women's Health, Prevention, 2.1 Biological and endogenous factors, Inflammatory and immune system, Good Health and Well Being, blood pressure, genome wide association studies, integrative genomics, regulatory networks, key drivers, Cardiovascular medicine and haematology
Abstract

Blood pressure (BP) is a highly heritable trait and a major cardiovascular disease risk factor. Genome wide association studies (GWAS) have implicated a number of susceptibility loci for systolic (SBP) and diastolic (DBP) blood pressure. However, a large portion of the heritability cannot be explained by the top GWAS loci and a comprehensive understanding of the underlying molecular mechanisms is still lacking. Here, we utilized an integrative genomics approach that leveraged multiple genetic and genomic datasets including (a) GWAS for SBP and DBP from the International Consortium for Blood Pressure (ICBP), (b) expression quantitative trait loci (eQTLs) from genetics of gene expression studies of human tissues related to BP, (c) knowledge-driven biological pathways, and (d) data-driven tissue-specific regulatory gene networks. Integration of these multidimensional datasets revealed tens of pathways and gene subnetworks in vascular tissues, liver, adipose, blood, and brain functionally associated with DBP and SBP. Diverse processes such as platelet production, insulin secretion/signaling, protein catabolism, cell adhesion and junction, immune and inflammation, and cardiac/smooth muscle contraction, were shared between DBP and SBP. Furthermore, "Wnt signaling" and "mammalian target of rapamycin (mTOR) signaling" pathways were found to be unique to SBP, while "cytokine network", and "tryptophan catabolism" to DBP. Incorporation of gene regulatory networks in our analysis informed on key regulator genes that orchestrate tissue-specific subnetworks of genes whose variants together explain ~20% of BP heritability. Our results shed light on the complex mechanisms underlying BP regulation and highlight potential novel targets and pathways for hypertension and cardiovascular diseases.

Published
2019

17. Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function.

Author

Wyss, Annah B, Sofer, Tamar, Lee, Mi Kyeong, Terzikhan, Natalie, Nguyen, Jennifer N, Lahousse, Lies, Latourelle, Jeanne C, Smith, Albert Vernon, Bartz, Traci M, Feitosa, Mary F, Gao, Wei, Ahluwalia, Tarunveer S, Tang, Wenbo, Oldmeadow, Christopher, Duan, Qing, de Jong, Kim, Wojczynski, Mary K, Wang, Xin-Qun, Noordam, Raymond, Hartwig, Fernando Pires, Jackson, Victoria E, Wang, Tianyuan, Obeidat, Ma'en, Hobbs, Brian D, Huan, Tianxiao, Gui, Hongsheng, Parker, Margaret M, Hu, Donglei, Mogil, Lauren S, Kichaev, Gleb, Jin, Jianping, Graff, Mariaelisa, Harris, Tamara B, Kalhan, Ravi, Heckbert, Susan R, Paternoster, Lavinia, Burkart, Kristin M, Liu, Yongmei, Holliday, Elizabeth G, Wilson, James G, Vonk, Judith M, Sanders, Jason L, Barr, R Graham, de Mutsert, Renée, Menezes, Ana Maria Baptista, Adams, Hieab HH, van den Berge, Maarten, Joehanes, Roby, Levin, Albert M, Liberto, Jennifer, Launer, Lenore J, Morrison, Alanna C, Sitlani, Colleen M, Celedón, Juan C, Kritchevsky, Stephen B, Scott, Rodney J, Christensen, Kaare, Rotter, Jerome I, Bonten, Tobias N, Wehrmeister, Fernando César, Bossé, Yohan, Xiao, Shujie, Oh, Sam, Franceschini, Nora, Brody, Jennifer A, Kaplan, Robert C, Lohman, Kurt, McEvoy, Mark, Province, Michael A, Rosendaal, Frits R, Taylor, Kent D, Nickle, David C, Williams, L Keoki, Burchard, Esteban G, Wheeler, Heather E, Sin, Don D, Gudnason, Vilmundur, North, Kari E, Fornage, Myriam, Psaty, Bruce M, Myers, Richard H, O'Connor, George, Hansen, Torben, Laurie, Cathy C, Cassano, Patricia A, Sung, Joohon, Kim, Woo Jin, Attia, John R, Lange, Leslie, Boezen, H Marike, Thyagarajan, Bharat, Rich, Stephen S, Mook-Kanamori, Dennis O, Horta, Bernardo Lessa, Uitterlinden, André G, Im, Hae Kyung, Cho, Michael H, Brusselle, Guy G, and Gharib, Sina A

Subjects
Lung, Humans, Lung Diseases, Pulmonary Disease, Chronic Obstructive, Genetic Predisposition to Disease, Vital Capacity, Forced Expiratory Volume, Regression Analysis, Sample Size, Smoking, Genomics, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Quantitative Trait Loci, African Continental Ancestry Group, Asian Americans, European Continental Ancestry Group, Hispanic Americans, Female, Male, Genome-Wide Association Study, Polymorphism, Single Nucleotide, Pulmonary Disease, Chronic Obstructive
Abstract

Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of lung function and clinical relevance of implicated loci.

Published
2018

18. Whole genome DNA and RNA sequencing of whole blood elucidates the genetic architecture of gene expression underlying a wide range of diseases

Author

Liu, Chunyu, Joehanes, Roby, Ma, Jiantao, Wang, Yuxuan, Sun, Xianbang, Keshawarz, Amena, Sooda, Meera, Huan, Tianxiao, Hwang, Shih-Jen, Bui, Helena, Tejada, Brandon, Munson, Peter J., Demirkale, Cumhur Y., Heard-Costa, Nancy L., Pitsillides, Achilleas N., Peloso, Gina M., Feolo, Michael, Sharopova, Nataliya, Vasan, Ramachandran S., and Levy, Daniel

Published
2022
Full Text
View/download PDF

20. Plasma Extracellular MicroRNAs Associated With Cardiovascular Disease Risk Factors in Middle‐Aged and Older Adults

Author

Karlin, Hannah, primary, Sooda, Meera, additional, Larson, Martin, additional, Rong, Jian, additional, Huan, Tianxiao, additional, Mens, Michelle M. J., additional, van Rooij, Frank J. A., additional, Ikram, M. Arfan, additional, Courchesne, Paul, additional, Freedman, Jane E., additional, Joehanes, Roby, additional, Mueller, Gregory P., additional, Kavousi, Maryam, additional, Ghanbari, Mohsen, additional, and Levy, Daniel, additional

Published
2024
Full Text
View/download PDF

23. DNA Methylation Analysis Identifies Loci for Blood Pressure Regulation

Author

Richard, Melissa A, Huan, Tianxiao, Ligthart, Symen, Gondalia, Rahul, Jhun, Min A, Brody, Jennifer A, Irvin, Marguerite R, Marioni, Riccardo, Shen, Jincheng, Tsai, Pei-Chien, Montasser, May E, Jia, Yucheng, Syme, Catriona, Salfati, Elias L, Boerwinkle, Eric, Guan, Weihua, Mosley, Thomas H, Bressler, Jan, Morrison, Alanna C, Liu, Chunyu, Mendelson, Michael M, Uitterlinden, André G, van Meurs, Joyce B, Consortium, BIOS, Heijmans, Bastiaan T, Hoen, Peter AC ’t, van Meurs, Joyce, Isaacs, Aaron, Jansen, Rick, Franke, Lude, Boomsma, Dorret I, Pool, René, van Dongen, Jenny, Hottenga, Jouke J, van Greevenbroek, Marleen MJ, Stehouwer, Coen DA, van der Kallen, Carla JH, Schalkwijk, Casper G, Wijmenga, Cisca, Zhernakova, Alexandra, Tigchelaar, Ettje F, Slagboom, P Eline, Beekman, Marian, Deelen, Joris, van Heemst, Diana, Veldink, Jan H, van den Berg, Leonard H, van Duijn, Cornelia M, Hofman, Albert, Jhamai, P Mila, Verbiest, Michael, Suchiman, H Eka D, Verkerk, Marijn, van der Breggen, Ruud, van Rooij, Jeroen, Lakenberg, Nico, Mei, Hailiang, van Iterson, Maarten, van Galen, Michiel, Bot, Jan, van ’t Hof, Peter, Deelen, Patrick, Nooren, Irene, Moed, Matthijs, Vermaat, Martijn, Zhernakova, Dasha V, Luijk, René, Bonder, Marc Jan, van Dijk, Freerk, Arindrarto, Wibowo, Kielbasa, Szymon M, Swertz, Morris A, van Zwet, Erik W, Franco, Oscar H, Zhang, Guosheng, Li, Yun, Stewart, James D, Bis, Joshua C, Psaty, Bruce M, Chen, Yii-Der Ida, Kardia, Sharon LR, Zhao, Wei, Turner, Stephen T, Absher, Devin, Aslibekyan, Stella, Starr, John M, McRae, Allan F, Hou, Lifang, Just, Allan C, Schwartz, Joel D, Vokonas, Pantel S, Menni, Cristina, Spector, Tim D, Shuldiner, Alan, Damcott, Coleen M, Rotter, Jerome I, Palmas, Walter, Liu, Yongmei, and Paus, Tomáš

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Human Genome, Biotechnology, Aetiology, 2.1 Biological and endogenous factors, Aged, Blood Pressure, CpG Islands, Cross-Sectional Studies, DNA Methylation, Epigenesis, Genetic, Genetic Variation, Genome-Wide Association Study, Humans, Mendelian Randomization Analysis, Middle Aged, Nerve Tissue Proteins, Quantitative Trait Loci, Tetraspanins, BIOS Consortium, DNA methylation, Mendelian randomization, blood pressure, epigenome-wide association study, gene expression, sequence variation, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Genome-wide association studies have identified hundreds of genetic variants associated with blood pressure (BP), but sequence variation accounts for a small fraction of the phenotypic variance. Epigenetic changes may alter the expression of genes involved in BP regulation and explain part of the missing heritability. We therefore conducted a two-stage meta-analysis of the cross-sectional associations of systolic and diastolic BP with blood-derived genome-wide DNA methylation measured on the Infinium HumanMethylation450 BeadChip in 17,010 individuals of European, African American, and Hispanic ancestry. Of 31 discovery-stage cytosine-phosphate-guanine (CpG) dinucleotides, 13 replicated after Bonferroni correction (discovery: N = 9,828, p < 1.0 × 10-7; replication: N = 7,182, p  30%) and independent of known BP genetic variants, explaining an additional 1.4% and 2.0% of the interindividual variation in systolic and diastolic BP, respectively. Bidirectional Mendelian randomization among up to 4,513 individuals of European ancestry from 4 cohorts suggested that methylation at cg08035323 (TAF1B-YWHAQ) influences BP, while BP influences methylation at cg00533891 (ZMIZ1), cg00574958 (CPT1A), and cg02711608 (SLC1A5). Gene expression analyses further identified six genes (TSPAN2, SLC7A11, UNC93B1, CPT1A, PTMS, and LPCAT3) with evidence of triangular associations between methylation, gene expression, and BP. Additional integrative Mendelian randomization analyses of gene expression and DNA methylation suggested that the expression of TSPAN2 is a putative mediator of association between DNA methylation at cg23999170 and BP. These findings suggest that heritable DNA methylation plays a role in regulating BP independently of previously known genetic variants.

Published
2017

24. Association of Body Mass Index with DNA Methylation and Gene Expression in Blood Cells and Relations to Cardiometabolic Disease: A Mendelian Randomization Approach.

Author

Mendelson, Michael M, Marioni, Riccardo E, Joehanes, Roby, Liu, Chunyu, Hedman, Åsa K, Aslibekyan, Stella, Demerath, Ellen W, Guan, Weihua, Zhi, Degui, Yao, Chen, Huan, Tianxiao, Willinger, Christine, Chen, Brian, Courchesne, Paul, Multhaup, Michael, Irvin, Marguerite R, Cohain, Ariella, Schadt, Eric E, Grove, Megan L, Bressler, Jan, North, Kari, Sundström, Johan, Gustafsson, Stefan, Shah, Sonia, McRae, Allan F, Harris, Sarah E, Gibson, Jude, Redmond, Paul, Corley, Janie, Murphy, Lee, Starr, John M, Kleinbrink, Erica, Lipovich, Leonard, Visscher, Peter M, Wray, Naomi R, Krauss, Ronald M, Fallin, Daniele, Feinberg, Andrew, Absher, Devin M, Fornage, Myriam, Pankow, James S, Lind, Lars, Fox, Caroline, Ingelsson, Erik, Arnett, Donna K, Boerwinkle, Eric, Liang, Liming, Levy, Daniel, and Deary, Ian J

Subjects
Leukocytes, Humans, Obesity, Body Mass Index, Oligonucleotide Array Sequence Analysis, DNA Methylation, Gene Expression Regulation, Epigenesis, Genetic, Aged, Female, Male, Lipid Metabolism, Coronary Artery Disease, Genome-Wide Association Study, Mendelian Randomization Analysis, Epigenesis, Genetic, General & Internal Medicine, Medical and Health Sciences
Abstract

BackgroundThe link between DNA methylation, obesity, and adiposity-related diseases in the general population remains uncertain.Methods and findingsWe conducted an association study of body mass index (BMI) and differential methylation for over 400,000 CpGs assayed by microarray in whole-blood-derived DNA from 3,743 participants in the Framingham Heart Study and the Lothian Birth Cohorts, with independent replication in three external cohorts of 4,055 participants. We examined variations in whole blood gene expression and conducted Mendelian randomization analyses to investigate the functional and clinical relevance of the findings. We identified novel and previously reported BMI-related differential methylation at 83 CpGs that replicated across cohorts; BMI-related differential methylation was associated with concurrent changes in the expression of genes in lipid metabolism pathways. Genetic instrumental variable analysis of alterations in methylation at one of the 83 replicated CpGs, cg11024682 (intronic to sterol regulatory element binding transcription factor 1 [SREBF1]), demonstrated links to BMI, adiposity-related traits, and coronary artery disease. Independent genetic instruments for expression of SREBF1 supported the findings linking methylation to adiposity and cardiometabolic disease. Methylation at a substantial proportion (16 of 83) of the identified loci was found to be secondary to differences in BMI. However, the cross-sectional nature of the data limits definitive causal determination.ConclusionsWe present robust associations of BMI with differential DNA methylation at numerous loci in blood cells. BMI-related DNA methylation and gene expression provide mechanistic insights into the relationship between DNA methylation, obesity, and adiposity-related diseases.

Published
2017

25. Shared genetic regulatory networks for cardiovascular disease and type 2 diabetes in multiple populations of diverse ethnicities in the United States

Author

Shu, Le, Chan, Kei Hang K, Zhang, Guanglin, Huan, Tianxiao, Kurt, Zeyneb, Zhao, Yuqi, Codoni, Veronica, Trégouët, David-Alexandre, Consortium, Cardiogenics, Yang, Jun, Wilson, James G, Luo, Xi, Levy, Daniel, Lusis, Aldons J, Liu, Simin, and Yang, Xia

Subjects
Biological Sciences, Genetics, Heart Disease, Diabetes, Human Genome, Biotechnology, Cardiovascular, 2.1 Biological and endogenous factors, Metabolic and endocrine, Good Health and Well Being, Adipocytes, Amino Acids, Branched-Chain, Animals, Cardiovascular Diseases, Caveolin 1, Diabetes Mellitus, Type 2, Disease Models, Animal, Ethnicity, Extracellular Matrix Proteins, Gene Expression Regulation, Gene Regulatory Networks, Genome-Wide Association Study, Glucose, Glycoproteins, Humans, Hydroxymethylglutaryl CoA Reductases, Insulin-Like Growth Factor I, Lipid Metabolism, Male, Mice, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Reproducibility of Results, United States, Cardiogenics Consortium, Developmental Biology
Abstract

Cardiovascular diseases (CVD) and type 2 diabetes (T2D) are closely interrelated complex diseases likely sharing overlapping pathogenesis driven by aberrant activities in gene networks. However, the molecular circuitries underlying the pathogenic commonalities remain poorly understood. We sought to identify the shared gene networks and their key intervening drivers for both CVD and T2D by conducting a comprehensive integrative analysis driven by five multi-ethnic genome-wide association studies (GWAS) for CVD and T2D, expression quantitative trait loci (eQTLs), ENCODE, and tissue-specific gene network models (both co-expression and graphical models) from CVD and T2D relevant tissues. We identified pathways regulating the metabolism of lipids, glucose, and branched-chain amino acids, along with those governing oxidation, extracellular matrix, immune response, and neuronal system as shared pathogenic processes for both diseases. Further, we uncovered 15 key drivers including HMGCR, CAV1, IGF1 and PCOLCE, whose network neighbors collectively account for approximately 35% of known GWAS hits for CVD and 22% for T2D. Finally, we cross-validated the regulatory role of the top key drivers using in vitro siRNA knockdown, in vivo gene knockout, and two Hybrid Mouse Diversity Panels each comprised of >100 strains. Findings from this in-depth assessment of genetic and functional data from multiple human cohorts provide strong support that common sets of tissue-specific molecular networks drive the pathogenesis of both CVD and T2D across ethnicities and help prioritize new therapeutic avenues for both CVD and T2D.

Published
2017

26. Epigenetic Patterns in Blood Associated With Lipid Traits Predict Incident Coronary Heart Disease Events and Are Enriched for Results From Genome-Wide Association Studies

Author

Hedman, Åsa K, Mendelson, Michael M, Marioni, Riccardo E, Gustafsson, Stefan, Joehanes, Roby, Irvin, Marguerite R, Zhi, Degui, Sandling, Johanna K, Yao, Chen, Liu, Chunyu, Liang, Liming, Huan, Tianxiao, McRae, Allan F, Demissie, Serkalem, Shah, Sonia, Starr, John M, Cupples, L Adrienne, Deloukas, Panos, Spector, Timothy D, Sundström, Johan, Krauss, Ronald M, Arnett, Donna K, Deary, Ian J, Lind, Lars, Levy, Daniel, and Ingelsson, Erik

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Atherosclerosis, Heart Disease - Coronary Heart Disease, Cardiovascular, Genetics, Heart Disease, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Aged, Biomarkers, Coronary Disease, CpG Islands, Cross-Sectional Studies, DNA Methylation, Dyslipidemias, Epigenesis, Genetic, Epigenomics, Europe, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Incidence, Lipid Metabolism, Lipids, Male, Metabolomics, Middle Aged, Phenotype, Prognosis, Prospective Studies, Quantitative Trait Loci, Risk Assessment, Risk Factors, United States, cardiovascular diseases, epigenomics, gene expression, lipids, Medical Biotechnology, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

BackgroundGenome-wide association studies have identified loci influencing circulating lipid concentrations in humans; further information on novel contributing genes, pathways, and biology may be gained through studies of epigenetic modifications.Methods and resultsTo identify epigenetic changes associated with lipid concentrations, we assayed genome-wide DNA methylation at cytosine-guanine dinucleotides (CpGs) in whole blood from 2306 individuals from 2 population-based cohorts, with replication of findings in 2025 additional individuals. We identified 193 CpGs associated with lipid levels in the discovery stage (P

Published
2017

27. Plasma Extracellular MicroRNAs Associated With Cardiovascular Disease Risk Factors in Middle-Aged and Older Adults

Author

Karlin, Hannah, Sooda, Meera, Larson, Martin, Rong, Jian, Huan, Tianxiao, Mens, Michelle M J, van Rooij, Frank J A, Ikram, M Arfan, Courchesne, Paul, Freedman, Jane E, Joehanes, Roby, Mueller, Gregory P, Kavousi, Maryam, Ghanbari, Mohsen, Levy, Daniel, Karlin, Hannah, Sooda, Meera, Larson, Martin, Rong, Jian, Huan, Tianxiao, Mens, Michelle M J, van Rooij, Frank J A, Ikram, M Arfan, Courchesne, Paul, Freedman, Jane E, Joehanes, Roby, Mueller, Gregory P, Kavousi, Maryam, Ghanbari, Mohsen, and Levy, Daniel

Abstract

BACKGROUND: Extracellular microRNAs (miRNAs) are a class of noncoding RNAs that remain stable in the extracellular milieu, where they contribute to various physiological and pathological processes by facilitating intercellular signaling. Previous studies have reported associations between miRNAs and cardiovascular diseases (CVDs); however, the plasma miRNA signatures of CVD and its risk factors have not been fully elucidated at the population level.METHODS AND RESULTS: Plasma miRNA levels were measured in 4440 FHS (Framingham Heart Study) participants. Linear regression analyses were conducted to test the cross-sectional associations of each miRNA with 8 CVD risk factors. Prospective analyses of the associations of miRNAs with new-onset obesity, hypertension, type 2 diabetes, CVD, and all-cause mortality were conducted using proportional hazards regression. Replication was carried out in 1999 RS (Rotterdam Study) participants. Pathway enrichment analyses were conducted and target genes were predicted for miRNAs associated with ≥5 risk factors in the FHS. In the FHS, 6 miRNAs (miR-193b-3p, miR-122-5p, miR-365a-3p, miR-194-5p, miR-192-5p, and miR-193a-5p) were associated with ≥5 risk factors. This miRNA signature was enriched for pathways associated with CVD and several genes annotated to these pathways were predicted targets of the identified miRNAs. Furthermore, miR-193b-3p, miR-194-5p, and miR-193a-5p were each associated with ≥2 risk factors in the RS. Prospective analysis revealed 8 miRNAs associated with all-cause mortality in the FHS.CONCLUSIONS: These findings highlight associations between miRNAs and CVD risk factors that may provide valuable insights into the underlying pathogenesis of CVD.

Published
2024

28. Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci

Author

Liu, Chunyu, Kraja, Aldi T, Smith, Jennifer A, Brody, Jennifer A, Franceschini, Nora, Bis, Joshua C, Rice, Kenneth, Morrison, Alanna C, Lu, Yingchang, Weiss, Stefan, Guo, Xiuqing, Palmas, Walter, Martin, Lisa W, Chen, Yii-Der Ida, Surendran, Praveen, Drenos, Fotios, Cook, James P, Auer, Paul L, Chu, Audrey Y, Giri, Ayush, Zhao, Wei, Jakobsdottir, Johanna, Lin, Li-An, Stafford, Jeanette M, Amin, Najaf, Mei, Hao, Yao, Jie, Voorman, Arend, Larson, Martin G, Grove, Megan L, Smith, Albert V, Hwang, Shih-Jen, Chen, Han, Huan, Tianxiao, Kosova, Gulum, Stitziel, Nathan O, Kathiresan, Sekar, Samani, Nilesh, Schunkert, Heribert, Deloukas, Panos, Li, Man, Fuchsberger, Christian, Pattaro, Cristian, Gorski, Mathias, Kooperberg, Charles, Papanicolaou, George J, Rossouw, Jacques E, Faul, Jessica D, Kardia, Sharon LR, Bouchard, Claude, Raffel, Leslie J, Uitterlinden, André G, Franco, Oscar H, Vasan, Ramachandran S, O'Donnell, Christopher J, Taylor, Kent D, Liu, Kiang, Bottinger, Erwin P, Gottesman, Omri, Daw, E Warwick, Giulianini, Franco, Ganesh, Santhi, Salfati, Elias, Harris, Tamara B, Launer, Lenore J, Dörr, Marcus, Felix, Stephan B, Rettig, Rainer, Völzke, Henry, Kim, Eric, Lee, Wen-Jane, Lee, I-Te, Sheu, Wayne H-H, Tsosie, Krystal S, Edwards, Digna R Velez, Liu, Yongmei, Correa, Adolfo, Weir, David R, Völker, Uwe, Ridker, Paul M, Boerwinkle, Eric, Gudnason, Vilmundur, Reiner, Alexander P, van Duijn, Cornelia M, Borecki, Ingrid B, Edwards, Todd L, Chakravarti, Aravinda, Rotter, Jerome I, Psaty, Bruce M, Loos, Ruth JF, Fornage, Myriam, Ehret, Georg B, Newton-Cheh, Christopher, Levy, Daniel, and Chasman, Daniel I

Subjects
Biological Sciences, Genetics, Cardiovascular, Hypertension, Prevention, Biotechnology, 2.1 Biological and endogenous factors, Aetiology, Blood Pressure, Exome, Genetic Variation, Genome, Human, Genome-Wide Association Study, Genotype, Humans, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, CHD Exome+ Consortium, ExomeBP Consortium, GoT2DGenes Consortium, T2D-GENES Consortium, Myocardial Infarction Genetics and CARDIoGRAM Exome Consortia, CKDGen Consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Meta-analyses of association results for blood pressure using exome-centric single-variant and gene-based tests identified 31 new loci in a discovery stage among 146,562 individuals, with follow-up and meta-analysis in 180,726 additional individuals (total n = 327,288). These blood pressure-associated loci are enriched for known variants for cardiometabolic traits. Associations were also observed for the aggregation of rare and low-frequency missense variants in three genes, NPR1, DBH, and PTPMT1. In addition, blood pressure associations at 39 previously reported loci were confirmed. The identified variants implicate biological pathways related to cardiometabolic traits, vascular function, and development. Several new variants are inferred to have roles in transcription or as hubs in protein-protein interaction networks. Genetic risk scores constructed from the identified variants were strongly associated with coronary disease and myocardial infarction. This large collection of blood pressure-associated loci suggests new therapeutic strategies for hypertension, emphasizing a link with cardiometabolic risk.

Published
2016

29. The transcriptional landscape of age in human peripheral blood.

Author

Peters, Marjolein J, Joehanes, Roby, Pilling, Luke C, Schurmann, Claudia, Conneely, Karen N, Powell, Joseph, Reinmaa, Eva, Sutphin, George L, Zhernakova, Alexandra, Schramm, Katharina, Wilson, Yana A, Kobes, Sayuko, Tukiainen, Taru, NABEC/UKBEC Consortium, Ramos, Yolande F, Göring, Harald HH, Fornage, Myriam, Liu, Yongmei, Gharib, Sina A, Stranger, Barbara E, De Jager, Philip L, Aviv, Abraham, Levy, Daniel, Murabito, Joanne M, Munson, Peter J, Huan, Tianxiao, Hofman, Albert, Uitterlinden, André G, Rivadeneira, Fernando, van Rooij, Jeroen, Stolk, Lisette, Broer, Linda, Verbiest, Michael MPJ, Jhamai, Mila, Arp, Pascal, Metspalu, Andres, Tserel, Liina, Milani, Lili, Samani, Nilesh J, Peterson, Pärt, Kasela, Silva, Codd, Veryan, Peters, Annette, Ward-Caviness, Cavin K, Herder, Christian, Waldenberger, Melanie, Roden, Michael, Singmann, Paula, Zeilinger, Sonja, Illig, Thomas, Homuth, Georg, Grabe, Hans-Jörgen, Völzke, Henry, Steil, Leif, Kocher, Thomas, Murray, Anna, Melzer, David, Yaghootkar, Hanieh, Bandinelli, Stefania, Moses, Eric K, Kent, Jack W, Curran, Joanne E, Johnson, Matthew P, Williams-Blangero, Sarah, Westra, Harm-Jan, McRae, Allan F, Smith, Jennifer A, Kardia, Sharon LR, Hovatta, Iiris, Perola, Markus, Ripatti, Samuli, Salomaa, Veikko, Henders, Anjali K, Martin, Nicholas G, Smith, Alicia K, Mehta, Divya, Binder, Elisabeth B, Nylocks, K Maria, Kennedy, Elizabeth M, Klengel, Torsten, Ding, Jingzhong, Suchy-Dicey, Astrid M, Enquobahrie, Daniel A, Brody, Jennifer, Rotter, Jerome I, Chen, Yii-Der I, Houwing-Duistermaat, Jeanine, Kloppenburg, Margreet, Slagboom, P Eline, Helmer, Quinta, den Hollander, Wouter, Bean, Shannon, Raj, Towfique, Bakhshi, Noman, Wang, Qiao Ping, Oyston, Lisa J, Psaty, Bruce M, Tracy, Russell P, Montgomery, Grant W, and Turner, Stephen T

Subjects
NABEC/UKBEC Consortium, Humans, Gene Expression Profiling, DNA Methylation, Aging, European Continental Ancestry Group, Transcriptome, Biomarkers
Abstract

Disease incidences increase with age, but the molecular characteristics of ageing that lead to increased disease susceptibility remain inadequately understood. Here we perform a whole-blood gene expression meta-analysis in 14,983 individuals of European ancestry (including replication) and identify 1,497 genes that are differentially expressed with chronological age. The age-associated genes do not harbor more age-associated CpG-methylation sites than other genes, but are instead enriched for the presence of potentially functional CpG-methylation sites in enhancer and insulator regions that associate with both chronological age and gene expression levels. We further used the gene expression profiles to calculate the 'transcriptomic age' of an individual, and show that differences between transcriptomic age and chronological age are associated with biological features linked to ageing, such as blood pressure, cholesterol levels, fasting glucose, and body mass index. The transcriptomic prediction model adds biological relevance and complements existing epigenetic prediction models, and can be used by others to calculate transcriptomic age in external cohorts.

Published
2015

30. Integrative network analysis reveals molecular mechanisms of blood pressure regulation.

Author

Huan, Tianxiao, Meng, Qingying, Saleh, Mohamed A, Norlander, Allison E, Joehanes, Roby, Zhu, Jun, Chen, Brian H, Zhang, Bin, Johnson, Andrew D, Ying, Saixia, Courchesne, Paul, Raghavachari, Nalini, Wang, Richard, Liu, Poching, International Consortium for Blood Pressure GWAS (ICBP), O'Donnell, Christopher J, Vasan, Ramachandran, Munson, Peter J, Madhur, Meena S, Harrison, David G, Yang, Xia, and Levy, Daniel

Subjects
International Consortium for Blood Pressure GWAS, Animals, Mice, Knockout, Humans, Mice, Hypertension, Disease Models, Animal, Intracellular Signaling Peptides and Proteins, Angiotensin II, RNA, Messenger, Body Mass Index, Linear Models, Cohort Studies, Sequence Analysis, RNA, Systems Biology, Blood Pressure, Polymorphism, Single Nucleotide, Adult, Aged, Middle Aged, Female, Male, Gene Regulatory Networks, Protein Interaction Domains and Motifs, Genome-Wide Association Study, Young Adult, Genetic Loci, Transcriptome, blood pressure, coexpression network, gene expression, hypertension, systems biology, Membrane Proteins, Prevention, Cardiovascular, Genetics, Human Genome, Biotechnology, 2.1 Biological and endogenous factors, Knockout, Disease Models, Animal, RNA, Messenger, Sequence Analysis, Polymorphism, Single Nucleotide, Bioinformatics, Other Biological Sciences, Biochemistry and Cell Biology
Abstract

Genome-wide association studies (GWAS) have identified numerous loci associated with blood pressure (BP). The molecular mechanisms underlying BP regulation, however, remain unclear. We investigated BP-associated molecular mechanisms by integrating BP GWAS with whole blood mRNA expression profiles in 3,679 individuals, using network approaches. BP transcriptomic signatures at the single-gene and the coexpression network module levels were identified. Four coexpression modules were identified as potentially causal based on genetic inference because expression-related SNPs for their corresponding genes demonstrated enrichment for BP GWAS signals. Genes from the four modules were further projected onto predefined molecular interaction networks, revealing key drivers. Gene subnetworks entailing molecular interactions between key drivers and BP-related genes were uncovered. As proof-of-concept, we validated SH2B3, one of the top key drivers, using Sh2b3(-/-) mice. We found that a significant number of genes predicted to be regulated by SH2B3 in gene networks are perturbed in Sh2b3(-/-) mice, which demonstrate an exaggerated pressor response to angiotensin II infusion. Our findings may help to identify novel targets for the prevention or treatment of hypertension.

Published
2015

31. A meta-analysis of gene expression signatures of blood pressure and hypertension.

Author

Huan, Tianxiao, Esko, Tõnu, Peters, Marjolein J, Pilling, Luke C, Schramm, Katharina, Schurmann, Claudia, Chen, Brian H, Liu, Chunyu, Joehanes, Roby, Johnson, Andrew D, Yao, Chen, Ying, Sai-Xia, Courchesne, Paul, Milani, Lili, Raghavachari, Nalini, Wang, Richard, Liu, Poching, Reinmaa, Eva, Dehghan, Abbas, Hofman, Albert, Uitterlinden, André G, Hernandez, Dena G, Bandinelli, Stefania, Singleton, Andrew, Melzer, David, Metspalu, Andres, Carstensen, Maren, Grallert, Harald, Herder, Christian, Meitinger, Thomas, Peters, Annette, Roden, Michael, Waldenberger, Melanie, Dörr, Marcus, Felix, Stephan B, Zeller, Tanja, International Consortium for Blood Pressure GWAS (ICBP), Vasan, Ramachandran, O'Donnell, Christopher J, Munson, Peter J, Yang, Xia, Prokisch, Holger, Völker, Uwe, van Meurs, Joyce BJ, Ferrucci, Luigi, and Levy, Daniel

Subjects
International Consortium for Blood Pressure GWAS, Humans, Hypertension, Genetic Predisposition to Disease, Gene Expression Regulation, Blood Pressure, Genotype, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Transcriptome, Cardiovascular, Aging, Genetics, Prevention, Human Genome, Biotechnology, 2.1 Biological and endogenous factors, Developmental Biology
Abstract

Genome-wide association studies (GWAS) have uncovered numerous genetic variants (SNPs) that are associated with blood pressure (BP). Genetic variants may lead to BP changes by acting on intermediate molecular phenotypes such as coded protein sequence or gene expression, which in turn affect BP variability. Therefore, characterizing genes whose expression is associated with BP may reveal cellular processes involved in BP regulation and uncover how transcripts mediate genetic and environmental effects on BP variability. A meta-analysis of results from six studies of global gene expression profiles of BP and hypertension in whole blood was performed in 7017 individuals who were not receiving antihypertensive drug treatment. We identified 34 genes that were differentially expressed in relation to BP (Bonferroni-corrected p

Published
2015

33. Integrative genomics reveals novel molecular pathways and gene networks for coronary artery disease.

Author

Mäkinen, Ville-Petteri, Civelek, Mete, Meng, Qingying, Zhang, Bin, Zhu, Jun, Levian, Candace, Huan, Tianxiao, Segrè, Ayellet V, Ghosh, Sujoy, Vivar, Juan, Nikpay, Majid, Stewart, Alexandre FR, Nelson, Christopher P, Willenborg, Christina, Erdmann, Jeanette, Blakenberg, Stefan, O'Donnell, Christopher J, März, Winfried, Laaksonen, Reijo, Epstein, Stephen E, Kathiresan, Sekar, Shah, Svati H, Hazen, Stanley L, Reilly, Muredach P, Coronary ARtery DIsease Genome-Wide Replication And Meta-Analysis (CARDIoGRAM) Consortium, Lusis, Aldons J, Samani, Nilesh J, Schunkert, Heribert, Quertermous, Thomas, McPherson, Ruth, Yang, Xia, and Assimes, Themistocles L

Subjects
Coronary ARtery DIsease Genome-Wide Replication And Meta-Analysis (CARDIoGRAM) Consortium, Animals, Humans, Mice, Genetic Predisposition to Disease, Genomics, Signal Transduction, Gene Expression Regulation, Gene Regulatory Networks, Coronary Artery Disease, Genome-Wide Association Study, Developmental Biology, Genetics
Abstract

The majority of the heritability of coronary artery disease (CAD) remains unexplained, despite recent successes of genome-wide association studies (GWAS) in identifying novel susceptibility loci. Integrating functional genomic data from a variety of sources with a large-scale meta-analysis of CAD GWAS may facilitate the identification of novel biological processes and genes involved in CAD, as well as clarify the causal relationships of established processes. Towards this end, we integrated 14 GWAS from the CARDIoGRAM Consortium and two additional GWAS from the Ottawa Heart Institute (25,491 cases and 66,819 controls) with 1) genetics of gene expression studies of CAD-relevant tissues in humans, 2) metabolic and signaling pathways from public databases, and 3) data-driven, tissue-specific gene networks from a multitude of human and mouse experiments. We not only detected CAD-associated gene networks of lipid metabolism, coagulation, immunity, and additional networks with no clear functional annotation, but also revealed key driver genes for each CAD network based on the topology of the gene regulatory networks. In particular, we found a gene network involved in antigen processing to be strongly associated with CAD. The key driver genes of this network included glyoxalase I (GLO1) and peptidylprolyl isomerase I (PPIL1), which we verified as regulatory by siRNA experiments in human aortic endothelial cells. Our results suggest genetic influences on a diverse set of both known and novel biological processes that contribute to CAD risk. The key driver genes for these networks highlight potential novel targets for further mechanistic studies and therapeutic interventions.

Published
2014

34. Genome-Wide Interaction Analysis with DASH Diet Score Identified Novel Loci for Systolic Blood Pressure

Author

Guirette, Melanie, primary, Lan, Jessie, additional, Mckeown, Nicola M, additional, Brown, Michael R., additional, Chen, Han, additional, De Vries, Paul S, additional, Kim, Hyunju, additional, Rebholz, Casey M., additional, Morrison, Alanna C., additional, Bartz, Traci Mae, additional, Fretts, Amanda, additional, Guo, Xiuqing, additional, Lemaitre, Rozenn N, additional, Liu, Ching-Ti, additional, Noordam, Raymond, additional, de Mutsert, Renée, additional, Rosendaal, Frits R., additional, Wang, Carol A, additional, Beilin, Lawrence J., additional, Mori, Trevor A., additional, Oddy, Wendy H, additional, Pennell, Craig E, additional, Chai, Jin-Fang, additional, Whitton, Clare, additional, van Dam, Rob M., additional, Liu, Jianjun, additional, Tai, E Shyong, additional, Sim, Xueling, additional, Neuhouser, Marian L., additional, Kooperberg, Charles, additional, Tinker, Lesley F., additional, Franceschini, Nora, additional, Huan, TianXiao, additional, Winkler, Thomas W, additional, Bentley, Amy R., additional, Gauderman, W. James, additional, Heerkens, Luc, additional, Tanaka, Toshiko, additional, Van Rooij, Jeroen, additional, Munroe, Patricia B., additional, Warren, Helen R., additional, Voortman, Trudy, additional, Chen, Honglei, additional, Rao, D.C., additional, Levy, Daniel, additional, and Ma, Jiantao, additional

Published
2023
Full Text
View/download PDF

35. Atrial natriuretic peptide is negatively regulated by microRNA-425

Author

Arora, Pankaj, Wu, Connie, Khan, Abigail May, Bloch, Donald B, Davis-Dusenbery, Brandi N, Ghorbani, Anahita, Spagnolli, Ester, Martinez, Andrew, Ryan, Allicia, Tainsh, Laurel T, Kim, Samuel, Rong, Jian, Huan, Tianxiao, Freedman, Jane E, Levy, Daniel, Miller, Karen K, Hata, Akiko, del Monte, Federica, Vandenwijngaert, Sara, Swinnen, Melissa, Janssens, Stefan, Holmes, Tara M, Buys, Emmanuel S, Bloch, Kenneth D, Newton-Cheh, Christopher, and Wang, Thomas J

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Biotechnology, Hypertension, Cardiovascular, 3' Untranslated Regions, Adult, Animals, Atrial Natriuretic Factor, COS Cells, Chlorocebus aethiops, Cyclic GMP, Female, Gene Expression, Gene Frequency, Genetic Association Studies, Humans, Male, MicroRNAs, Polymorphism, Single Nucleotide, RNA Interference, Sequence Analysis, DNA, Sodium Chloride, Dietary, Young Adult, Medical and Health Sciences, Immunology, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Numerous common genetic variants have been linked to blood pressure, but no underlying mechanism has been elucidated. Population studies have revealed that the variant rs5068 (A/G) in the 3' untranslated region of NPPA, the gene encoding atrial natriuretic peptide (ANP), is associated with blood pressure. We selected individuals on the basis of rs5068 genotype (AG vs. AA) and fed them a low- or high-salt diet for 1 week, after which they were challenged with an intravenous saline infusion. On both diets, before and after saline administration, ANP levels were up to 50% higher in AG individuals than in AA individuals, a difference comparable to the changes induced by high-salt diet or saline infusion. In contrast, B-type natriuretic peptide levels did not differ by rs5068 genotype. We identified a microRNA, miR-425, that is expressed in human atria and ventricles and is predicted to bind the sequence spanning rs5068 for the A, but not the G, allele. miR-425 silenced NPPA mRNA in an allele-specific manner, with the G allele conferring resistance to miR-425. This study identifies miR-425 as a regulator of ANP production, raising the possibility that miR-425 antagonists could be used to treat disorders of salt overload, including hypertension and heart failure.

Published
2013

36. Mir-30d Regulates Cardiac Remodeling by Intracellular and Paracrine Signaling

Author

Li, Jin, Salvador, Ane M., Li, Guoping, Valkov, Nedyalka, Ziegler, Olivia, Yeri, Ashish, Yang Xiao, Chun, Meechoovet, Bessie, Alsop, Eric, Rodosthenous, Rodosthenis S., Kundu, Piyusha, Huan, Tianxiao, Levy, Daniel, Tigges, John, Pico, Alexander R., Ghiran, Ionita, Silverman, Michael G., Meng, Xiangmin, Kitchen, Robert, Xu, Jiahong, Van Keuren-Jensen, Kendall, Shah, Ravi, Xiao, Junjie, and Das, Saumya

Published
2021
Full Text
View/download PDF

37. Contribution of blood DNA methylation to the association between smoking and lung cancer

Author

Relloso, Arce Domingo, primary, Joehanes, Roby, additional, Hernandez, Zulema Rodriguez, additional, Lahousse, Lies, additional, Haack, Karin, additional, Fallin, Daniele, additional, Herreros, Miguel, additional, Umans, Jason G, additional, Best, Lyle G, additional, Huan, Tianxiao, additional, Liu, Chunyu, additional, Ma, Jiantao, additional, Yao, Chen, additional, Jerolon, Allan, additional, Edo, Jose D Bermudez, additional, Cole, Shelley A, additional, Rhoades, Dorothy A, additional, Levy, Daniel, additional, Acien, Ana Navas, additional, and Plaza, Maria Tellez, additional

Published
2023
Full Text
View/download PDF

38. Abstract 077: Protein Biomarkers Of Hypertension

Author

Aggarwal, Mohit, primary, Lee, Dong Heon, additional, Huan, Tianxiao, additional, Jenna, Mcneil, additional, Courchesne, Paul, additional, Joehanes, Roby, additional, Dupuis, Josee, additional, O'Connor, George, additional, and Levy, Daniel, additional

Published
2023
Full Text
View/download PDF

39. Epigenome-wide DNA methylation association study of circulating IgE levels identifies novel targets for asthma

Author

Recto, Kathryn, primary, Kachroo, Priyadarshini, additional, Huan, Tianxiao, additional, Van Den Berg, David, additional, Lee, Gha Young, additional, Bui, Helena, additional, Lee, Dong Heon, additional, Gereige, Jessica, additional, Yao, Chen, additional, Hwang, Shih-Jen, additional, Joehanes, Roby, additional, Weiss, Scott T., additional, O’Connor, George T., additional, Levy, Daniel, additional, DeMeo, Dawn L., additional, Abe, Namiko, additional, Abecasis, Gonçalo, additional, Aguet, Francois, additional, Albert, Christine, additional, Almasy, Laura, additional, Alonso, Alvaro, additional, Ament, Seth, additional, Anderson, Peter, additional, Anugu, Pramod, additional, Applebaum-Bowden, Deborah, additional, Ardlie, Kristin, additional, Arking, Dan, additional, Arnett, Donna K., additional, Ashley-Koch, Allison, additional, Aslibekyan, Stella, additional, Assimes, Tim, additional, Auer, Paul, additional, Avramopoulos, Dimitrios, additional, Ayas, Najib, additional, Balasubramanian, Adithya, additional, Barnard, John, additional, Barnes, Kathleen, additional, Barr, R. Graham, additional, Barron-Casella, Emily, additional, Barwick, Lucas, additional, Beaty, Terri, additional, Beck, Gerald, additional, Becker, Diane, additional, Becker, Lewis, additional, Beer, Rebecca, additional, Beitelshees, Amber, additional, Benjamin, Emelia, additional, Benos, Takis, additional, Bezerra, Marcos, additional, Bielak, Larry, additional, Bis, Joshua, additional, Blackwell, Thomas, additional, Blangero, John, additional, Blue, Nathan, additional, Boerwinkle, Eric, additional, Bowden, Donald W., additional, Bowler, Russell, additional, Brody, Jennifer, additional, Broeckel, Ulrich, additional, Broome, Jai, additional, Brown, Deborah, additional, Bunting, Karen, additional, Burchard, Esteban, additional, Bustamante, Carlos, additional, Buth, Erin, additional, Cade, Brian, additional, Cardwell, Jonathan, additional, Carey, Vincent, additional, Carrier, Julie, additional, Carson, April P., additional, Carty, Cara, additional, Casaburi, Richard, additional, Casas Romero, Juan P., additional, Casella, James, additional, Castaldi, Peter, additional, Chaffin, Mark, additional, Chang, Christy, additional, Chang, Yi-Cheng, additional, Chasman, Daniel, additional, Chavan, Sameer, additional, Chen, Bo-Juen, additional, Chen, Wei-Min, additional, Ida Chen, Yii-Der, additional, Cho, Michael, additional, Choi, Seung Hoan, additional, Chuang, Lee-Ming, additional, Chung, Mina, additional, Chung, Ren-Hua, additional, Clish, Clary, additional, Comhair, Suzy, additional, Conomos, Matthew, additional, Cornell, Elaine, additional, Correa, Adolfo, additional, Crandall, Carolyn, additional, Crapo, James, additional, Cupples, L. Adrienne, additional, Curran, Joanne, additional, Curtis, Jeffrey, additional, Custer, Brian, additional, Damcott, Coleen, additional, Darbar, Dawood, additional, David, Sean, additional, Davis, Colleen, additional, Daya, Michelle, additional, de Andrade, Mariza, additional, de las Fuentes, Lisa, additional, de Vries, Paul, additional, DeBaun, Michael, additional, Deka, Ranjan, additional, DeMeo, Dawn, additional, Devine, Scott, additional, Dinh, Huyen, additional, Doddapaneni, Harsha, additional, Duan, Qing, additional, Dugan-Perez, Shannon, additional, Duggirala, Ravi, additional, Durda, Jon Peter, additional, Dutcher, Susan K., additional, Eaton, Charles, additional, Ekunwe, Lynette, additional, El Boueiz, Adel, additional, Ellinor, Patrick, additional, Emery, Leslie, additional, Erzurum, Serpil, additional, Farber, Charles, additional, Farek, Jesse, additional, Fingerlin, Tasha, additional, Flickinger, Matthew, additional, Fornage, Myriam, additional, Franceschini, Nora, additional, Frazar, Chris, additional, Fu, Mao, additional, Fullerton, Stephanie M., additional, Fulton, Lucinda, additional, Gabriel, Stacey, additional, Gan, Weiniu, additional, Gao, Shanshan, additional, Gao, Yan, additional, Gass, Margery, additional, Geiger, Heather, additional, Gelb, Bruce, additional, Geraci, Mark, additional, Germer, Soren, additional, Gerszten, Robert, additional, Ghosh, Auyon, additional, Gibbs, Richard, additional, Gignoux, Chris, additional, Gladwin, Mark, additional, Glahn, David, additional, Gogarten, Stephanie, additional, Gong, Da-Wei, additional, Goring, Harald, additional, Graw, Sharon, additional, Gray, Kathryn J., additional, Grine, Daniel, additional, Gross, Colin, additional, Gu, C. Charles, additional, Guan, Yue, additional, Guo, Xiuqing, additional, Gupta, Namrata, additional, Haessler, Jeff, additional, Hall, Michael, additional, Han, Yi, additional, Hanly, Patrick, additional, Harris, Daniel, additional, Hawley, Nicola L., additional, He, Jiang, additional, Heavner, Ben, additional, Heckbert, Susan, additional, Hernandez, Ryan, additional, Herrington, David, additional, Hersh, Craig, additional, Hidalgo, Bertha, additional, Hixson, James, additional, Hobbs, Brian, additional, Hokanson, John, additional, Hong, Elliott, additional, Hoth, Karin, additional, Hsiung, Chao (Agnes), additional, Hu, Jianhong, additional, Hung, Yi-Jen, additional, Huston, Haley, additional, Hwu, Chii Min, additional, Irvin, Marguerite Ryan, additional, Jackson, Rebecca, additional, Jain, Deepti, additional, Jaquish, Cashell, additional, Johnsen, Jill, additional, Johnson, Andrew, additional, Johnson, Craig, additional, Johnston, Rich, additional, Jones, Kimberly, additional, Kang, Hyun Min, additional, Kaplan, Robert, additional, Kardia, Sharon, additional, Kelly, Shannon, additional, Kenny, Eimear, additional, Kessler, Michael, additional, Khan, Alyna, additional, Khan, Ziad, additional, Kim, Wonji, additional, Kimoff, John, additional, Kinney, Greg, additional, Konkle, Barbara, additional, Kooperberg, Charles, additional, Kramer, Holly, additional, Lange, Christoph, additional, Lange, Ethan, additional, Lange, Leslie, additional, Laurie, Cathy, additional, Laurie, Cecelia, additional, LeBoff, Meryl, additional, Lee, Jiwon, additional, Lee, Sandra, additional, Lee, Wen-Jane, additional, LeFaive, Jonathon, additional, Levine, David, additional, Lewis, Joshua, additional, Li, Xiaohui, additional, Li, Yun, additional, Lin, Henry, additional, Lin, Honghuang, additional, Lin, Xihong, additional, Liu, Simin, additional, Liu, Yongmei, additional, Liu, Yu, additional, Loos, Ruth J.F., additional, Lubitz, Steven, additional, Lunetta, Kathryn, additional, Luo, James, additional, Magalang, Ulysses, additional, Mahaney, Michael, additional, Make, Barry, additional, Manichaikul, Ani, additional, Manning, Alisa, additional, Manson, JoAnn, additional, Martin, Lisa, additional, Marton, Melissa, additional, Mathai, Susan, additional, Mathias, Rasika, additional, May, Susanne, additional, McArdle, Patrick, additional, McDonald, Merry-Lynn, additional, McFarland, Sean, additional, McGarvey, Stephen, additional, McGoldrick, Daniel, additional, McHugh, Caitlin, additional, McNeil, Becky, additional, Mei, Hao, additional, Meigs, James, additional, Menon, Vipin, additional, Mestroni, Luisa, additional, Metcalf, Ginger, additional, Meyers, Deborah A., additional, Mignot, Emmanuel, additional, Mikulla, Julie, additional, Min, Nancy, additional, Minear, Mollie, additional, Minster, Ryan L., additional, Mitchell, Braxton D., additional, Moll, Matt, additional, Momin, Zeineen, additional, Montasser, May E., additional, Montgomery, Courtney, additional, Muzny, Donna, additional, Mychaleckyj, Josyf C., additional, Nadkarni, Girish, additional, Naik, Rakhi, additional, Naseri, Take, additional, Natarajan, Pradeep, additional, Nekhai, Sergei, additional, Nelson, Sarah C., additional, Neltner, Bonnie, additional, Nessner, Caitlin, additional, Nickerson, Deborah, additional, Nkechinyere, Osuji, additional, North, Kari, additional, O'Connell, Jeff, additional, O'Connor, Tim, additional, Ochs-Balcom, Heather, additional, Okwuonu, Geoffrey, additional, Pack, Allan, additional, Paik, David T., additional, Palmer, Nicholette, additional, Pankow, James, additional, Papanicolaou, George, additional, Parker, Cora, additional, Peloso, Gina, additional, Peralta, Juan Manuel, additional, Perez, Marco, additional, Perry, James, additional, Peters, Ulrike, additional, Peyser, Patricia, additional, Phillips, Lawrence S., additional, Pleiness, Jacob, additional, Pollin, Toni, additional, Post, Wendy, additional, Powers Becker, Julia, additional, Preethi Boorgula, Meher, additional, Preuss, Michael, additional, Psaty, Bruce, additional, Qasba, Pankaj, additional, Qiao, Dandi, additional, Qin, Zhaohui, additional, Rafaels, Nicholas, additional, Raffield, Laura, additional, Rajendran, Mahitha, additional, Ramachandran, Vasan S., additional, Rao, D.C., additional, Rasmussen-Torvik, Laura, additional, Ratan, Aakrosh, additional, Redline, Susan, additional, Reed, Robert, additional, Reeves, Catherine, additional, Regan, Elizabeth, additional, Reiner, Alex, additional, Reupena, Muagututi‘a Sefuiva, additional, Rice, Ken, additional, Rich, Stephen, additional, Robillard, Rebecca, additional, Robine, Nicolas, additional, Roden, Dan, additional, Roselli, Carolina, additional, Rotter, Jerome, additional, Ruczinski, Ingo, additional, Runnels, Alexi, additional, Russell, Pamela, additional, Ruuska, Sarah, additional, Ryan, Kathleen, additional, Sabino, Ester Cerdeira, additional, Saleheen, Danish, additional, Salimi, Shabnam, additional, Salvi, Sejal, additional, Salzberg, Steven, additional, Sandow, Kevin, additional, Sankaran, Vijay G., additional, Santibanez, Jireh, additional, Schwander, Karen, additional, Schwartz, David, additional, Sciurba, Frank, additional, Seidman, Christine, additional, Seidman, Jonathan, additional, Sériès, Frédéric, additional, Sheehan, Vivien, additional, Sherman, Stephanie L., additional, Shetty, Amol, additional, Shetty, Aniket, additional, Sheu, Wayne Hui-Heng, additional, Shoemaker, M. Benjamin, additional, Silver, Brian, additional, Silverman, Edwin, additional, Skomro, Robert, additional, Smith, Albert Vernon, additional, Smith, Jennifer, additional, Smith, Josh, additional, Smith, Nicholas, additional, Smith, Tanja, additional, Smoller, Sylvia, additional, Snively, Beverly, additional, Snyder, Michael, additional, Sofer, Tamar, additional, Sotoodehnia, Nona, additional, Stilp, Adrienne M., additional, Storm, Garrett, additional, Streeten, Elizabeth, additional, Su, Jessica Lasky, additional, Sung, Yun Ju, additional, Sylvia, Jody, additional, Szpiro, Adam, additional, Taliun, Daniel, additional, Tang, Hua, additional, Taub, Margaret, additional, Taylor, Kent, additional, Taylor, Matthew, additional, Taylor, Simeon, additional, Telen, Marilyn, additional, Thornton, Timothy A., additional, Threlkeld, Machiko, additional, Tinker, Lesley, additional, Tirschwell, David, additional, Tishkoff, Sarah, additional, Tiwari, Hemant, additional, Tong, Catherine, additional, Tracy, Russell, additional, Tsai, Michael, additional, Vaidya, Dhananjay, additional, VandeHaar, Peter, additional, Vrieze, Scott, additional, Walker, Tarik, additional, Wallace, Robert, additional, Walts, Avram, additional, Wang, Fei Fei, additional, Wang, Heming, additional, Wang, Jiongming, additional, Watson, Karol, additional, Watt, Jennifer, additional, Weeks, Daniel E., additional, Weinstock, Joshua, additional, Weir, Bruce, additional, Weng, Lu-Chen, additional, Wessel, Jennifer, additional, Willer, Cristen, additional, Williams, Kayleen, additional, Williams, L. Keoki, additional, Williams, Scott, additional, Wilson, Carla, additional, Wilson, James, additional, Winterkorn, Lara, additional, Wong, Quenna, additional, Wu, Baojun, additional, Wu, Joseph, additional, Xu, Huichun, additional, Yanek, Lisa, additional, Yang, Ivana, additional, Yu, Ketian, additional, Zekavat, Seyedeh Maryam, additional, Zhang, Yingze, additional, Zhao, Snow Xueyan, additional, Zhao, Wei, additional, Zhu, Xiaofeng, additional, Ziv, Elad, additional, Zody, Michael, additional, and Zoellner, Sebastian, additional

Published
2023
Full Text
View/download PDF

41. Circulating Metabolites May Illustrate Relationship of Alcohol Consumption with Cardiovascular Disease

Author

Li, Yi, primary, Wang, Mengyao, additional, Liu, Xue, additional, Rong, Jian, additional, Miller, Patricia Emogene, additional, Joehanes, Roby, additional, Huan, Tianxiao, additional, Guo, Xiuqing, additional, Rotter, Jerome, additional, Smith, Jennifer, additional, Yu, Bing, additional, Nayor, Matthew, additional, Levy, Daniel, additional, Liu, Chunyu, additional, and Ma, Jiantao, additional

Published
2023
Full Text
View/download PDF

42. Genome-Wide Interaction Analysis with DASH Diet Score Identified Novel Loci for Systolic Blood Pressure

Author

Guirette, Mélanie, Lan, Jessie, McKeown, Nicola, Brown, Michael R, Chen, Han, DE Vries, Paul S, Kim, Hyunju, Rebholz, Casey M, Morrison, Alanna C, Bartz, Traci M, Fretts, Amanda M, Guo, Xiuqing, Lemaitre, Rozenn N, Liu, Ching-Ti, Noordam, Raymond, DE Mutsert, Renée, Rosendaal, Frits R, Wang, Carol A, Beilin, Lawrence, Mori, Trevor A, Oddy, Wendy H, Pennell, Craig E, Chai, Jin Fang, Whitton, Clare, VAN Dam, Rob M, Liu, Jianjun, Tai, E Shyong, Sim, Xueling, Neuhouser, Marian L, Kooperberg, Charles, Tinker, Lesley, Franceschini, Nora, Huan, Tianxiao, Winkler, Thomas W, Bentley, Amy R, Gauderman, W James, Heerkens, Luc, Tanaka, Toshiko, van Rooij, Jeroen, Munroe, Patricia B, Warren, Helen R, Voortman, Trudy, Chen, Honglei, Rao, D C, Levy, Daniel, Ma, Jiantao, Guirette, Mélanie, Lan, Jessie, McKeown, Nicola, Brown, Michael R, Chen, Han, DE Vries, Paul S, Kim, Hyunju, Rebholz, Casey M, Morrison, Alanna C, Bartz, Traci M, Fretts, Amanda M, Guo, Xiuqing, Lemaitre, Rozenn N, Liu, Ching-Ti, Noordam, Raymond, DE Mutsert, Renée, Rosendaal, Frits R, Wang, Carol A, Beilin, Lawrence, Mori, Trevor A, Oddy, Wendy H, Pennell, Craig E, Chai, Jin Fang, Whitton, Clare, VAN Dam, Rob M, Liu, Jianjun, Tai, E Shyong, Sim, Xueling, Neuhouser, Marian L, Kooperberg, Charles, Tinker, Lesley, Franceschini, Nora, Huan, Tianxiao, Winkler, Thomas W, Bentley, Amy R, Gauderman, W James, Heerkens, Luc, Tanaka, Toshiko, van Rooij, Jeroen, Munroe, Patricia B, Warren, Helen R, Voortman, Trudy, Chen, Honglei, Rao, D C, Levy, Daniel, and Ma, Jiantao

Abstract

OBJECTIVE: We examined interactions between genotype and a Dietary Approaches to Stop Hypertension (DASH) diet score in relation to systolic blood pressure (SBP).METHODS: We analyzed up to 9,420,585 biallelic imputed single nucleotide polymorphisms (SNPs) in up to 127,282 individuals of six population groups (91% of European population) from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (CHARGE; n=35,660) and UK Biobank (n=91,622) and performed European population-specific and cross-population meta-analyses.RESULTS: We identified three loci in European-specific analyses and an additional four loci in cross-population analyses at P for interaction < 5e-8. We observed a consistent interaction between rs117878928 at 15q25.1 (minor allele frequency = 0.03) and the DASH diet score (P for interaction = 4e-8; P for heterogeneity = 0.35) in European population, where the interaction effect size was 0.42±0.09 mm Hg (P for interaction = 9.4e-7) and 0.20±0.06 mm Hg (P for interaction = 0.001) in CHARGE and the UK Biobank, respectively. The 1 Mb region surrounding rs117878928 was enriched with cis-expression quantitative trait loci (eQTL) variants (P = 4e-273) and cis-DNA methylation quantitative trait loci (mQTL) variants (P = 1e-300). While the closest gene for rs117878928 is MTHFS, the highest narrow sense heritability accounted by SNPs potentially interacting with the DASH diet score in this locus was for gene ST20 at 15q25.1. CONCLUSION: We demonstrated gene-DASH diet score interaction effects on SBP in several loci. Studies with larger diverse populations are needed to validate our findings.

Published
2023

46. Transcriptome-wide association study of circulating IgE levels identifies novel targets for asthma and allergic diseases

Author

Recto, Kathryn A., primary, Huan, Tianxiao, additional, Lee, Dong Heon, additional, Lee, Gha Young, additional, Gereige, Jessica, additional, Yao, Chen, additional, Hwang, Shih-Jen, additional, Joehanes, Roby, additional, Kelly, Rachel S., additional, Lasky-Su, Jessica, additional, O’Connor, George, additional, and Levy, Daniel, additional

Published
2023
Full Text
View/download PDF

47. Opioid medication use and blood DNA methylation: epigenome-wide association meta-analysis

Author

Lee, Mikyeong, primary, Joehanes, Roby, additional, McCartney, Daniel L, additional, Kho, Minjung, additional, Hüls, Anke, additional, Wyss, Annah B, additional, Liu, Chunyu, additional, Walker, Rosie M, additional, R Kardia, Sharon L, additional, Wingo, Thomas S, additional, Burkholder, Adam, additional, Ma, Jiantao, additional, Campbell, Archie, additional, Wingo, Aliza P, additional, Huan, Tianxiao, additional, Sikdar, Sinjini, additional, Keshawarz, Amena, additional, Bennett, David A, additional, Smith, Jennifer A, additional, Evans, Kathryn L, additional, Levy, Daniel, additional, and London, Stephanie J, additional

Published
2023
Full Text
View/download PDF

48. Transcriptome-wide association study of circulating IgE levels identifies novel targets for asthma and allergic diseases

Author

Joehanes Roby, O’Connor George, Levy Daniel, Lasky-Su Jessica, Yao Chen, Recto Kathryn, Huan Tianxiao, Lee Dong Heon, Lee Gha Young, Hwang Shih-Jen, Gereige Jessica, and Rachel S. Kelly

Subjects
biology, Immunology, Immunoglobulin E, medicine.disease, Transcriptome, Immune system, Genetic epidemiology, Mendelian randomization, Gene expression, biology.protein, medicine, Immunology and Allergy, Gene, Asthma
Abstract

Measurement of circulating immunoglobulin E (IgE) concentration is helpful for diagnosing and treating asthma and allergic diseases. Identifying gene expression signatures associated with IgE might elucidate novel pathways for IgE regulation. To this end, we performed a discovery transcriptome-wide association study to identify differentially expressed genes associated with circulating IgE levels in whole-blood derived RNA from 5,345 participants in the Framingham Heart Study across 17,873 mRNA gene-level transcripts. We identified 216 significant transcripts at a false discovery rate CLC, CCDC21, S100A13, and GCNT1) as putatively causal (pGCNT1 (beta=1.5, p=0.01)—which is a top result in the MR analysis of expression in relation to asthma and allergic diseases—plays a role in regulating T helper type 1 cell homing, lymphocyte trafficking, and B cell differentiation. Our findings build upon prior knowledge of IgE regulation and provide a deeper understanding of underlying molecular mechanisms. The IgE-associated genes that we identified—particularly those implicated in MR analysis—can be explored as promising therapeutic targets for asthma and IgE-related diseases.

Published
2023
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results