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4. Whole-exome sequencing study identifies four novel gene loci associated with diabetic kidney disease.

Author

Pan, Yang, Sun, Xiao, Mi, Xuenan, Huang, Zhijie, Hsu, Yenchih, Hixson, James, Munzy, Donna, Metcalf, Ginger, Franceschini, Nora, Tin, Adrienne, Köttgen, Anna, Francis, Michael, Brody, Jennifer, Kestenbaum, Bryan, Sitlani, Colleen, Mychaleckyj, Josyf, Kramer, Holly, Lange, Leslie, Guo, Xiuqing, Hwang, Shih-Jen, Irvin, Marguerite, Smith, Jennifer, Yanek, Lisa, Vaidya, Dhananjay, Chen, Yii-Der, Fornage, Myriam, Lloyd-Jones, Donald, Hou, Lifang, Mathias, Rasika, Mitchell, Braxton, Peyser, Patricia, Kardia, Sharon, Arnett, Donna, Correa, Adolfo, Raffield, Laura, Vasan, Ramachandran, Cupple, L, Levy, Daniel, Kaplan, Robert, North, Kari, Kooperberg, Charles, Reiner, Alexander, Psaty, Bruce, Tracy, Russell, Gibbs, Richard, Morrison, Alanna, Feldman, Harold, Boerwinkle, Eric, He, Jiang, Kelly, Tanika, and Rotter, Jerome

Subjects
Humans, Aminopeptidases, Diabetes Mellitus, Diabetic Nephropathies, Exome Sequencing, Kidney, Renal Insufficiency, Chronic
Abstract

Diabetic kidney disease (DKD) is recognized as an important public health challenge. However, its genomic mechanisms are poorly understood. To identify rare variants for DKD, we conducted a whole-exome sequencing (WES) study leveraging large cohorts well-phenotyped for chronic kidney disease and diabetes. Our two-stage WES study included 4372 European and African ancestry participants from the Chronic Renal Insufficiency Cohort and Atherosclerosis Risk in Communities studies (stage 1) and 11 487 multi-ancestry Trans-Omics for Precision Medicine participants (stage 2). Generalized linear mixed models, which accounted for genetic relatedness and adjusted for age, sex and ancestry, were used to test associations between single variants and DKD. Gene-based aggregate rare variant analyses were conducted using an optimized sequence kernel association test implemented within our mixed model framework. We identified four novel exome-wide significant DKD-related loci through initiating diabetes. In single-variant analyses, participants carrying a rare, in-frame insertion in the DIS3L2 gene (rs141560952) exhibited a 193-fold increased odds [95% confidence interval (CI): 33.6, 1105] of DKD compared with noncarriers (P = 3.59 × 10-9). Likewise, each copy of a low-frequency KRT6B splice-site variant (rs425827) conferred a 5.31-fold higher odds (95% CI: 3.06, 9.21) of DKD (P = 2.72 × 10-9). Aggregate gene-based analyses further identified ERAP2 (P = 4.03 × 10-8) and NPEPPS (P = 1.51 × 10-7), which are both expressed in the kidney and implicated in renin-angiotensin-aldosterone system modulated immune response. In the largest WES study of DKD, we identified novel rare variant loci attaining exome-wide significance. These findings provide new insights into the molecular mechanisms underlying DKD.

Published
2023

5. Insights From a Large-Scale Whole-Genome Sequencing Study of Systolic Blood Pressure, Diastolic Blood Pressure, and Hypertension

Author

Kelly, Tanika N, Sun, Xiao, He, Karen Y, Brown, Michael R, Taliun, Sarah A Gagliano, Hellwege, Jacklyn N, Irvin, Marguerite R, Mi, Xuenan, Brody, Jennifer A, Franceschini, Nora, Guo, Xiuqing, Hwang, Shih-Jen, de Vries, Paul S, Gao, Yan, Moscati, Arden, Nadkarni, Girish N, Yanek, Lisa R, Elfassy, Tali, Smith, Jennifer A, Chung, Ren-Hua, Beitelshees, Amber L, Patki, Amit, Aslibekyan, Stella, Blobner, Brandon M, Peralta, Juan M, Assimes, Themistocles L, Palmas, Walter R, Liu, Chunyu, Bress, Adam P, Huang, Zhijie, Becker, Lewis C, Hwa, Chii-Min, O’Connell, Jeffrey R, Carlson, Jenna C, Warren, Helen R, Das, Sayantan, Giri, Ayush, Martin, Lisa W, Johnson, W Craig, Fox, Ervin R, Bottinger, Erwin P, Razavi, Alexander C, Vaidya, Dhananjay, Chuang, Lee-Ming, Chang, Yen-Pei C, Naseri, Take, Jain, Deepti, Kang, Hyun Min, Hung, Adriana M, Srinivasasainagendra, Vinodh, Snively, Beverly M, Gu, Dongfeng, Montasser, May E, Reupena, Muagututi A Sefuiva, Heavner, Benjamin D, LeFaive, Jonathon, Hixson, James E, Rice, Kenneth M, Wang, Fei Fei, Nielsen, Jonas B, Huang, Jianfeng, Khan, Alyna T, Zhou, Wei, Nierenberg, Jovia L, Laurie, Cathy C, Armstrong, Nicole D, Shi, Mengyao, Pan, Yang, Stilp, Adrienne M, Emery, Leslie, Wong, Quenna, Hawley, Nicola L, Minster, Ryan L, Curran, Joanne E, Munroe, Patricia B, Weeks, Daniel E, North, Kari E, Tracy, Russell P, Kenny, Eimear E, Shimbo, Daichi, Chakravarti, Aravinda, Rich, Stephen S, Reiner, Alex P, Blangero, John, Redline, Susan, Mitchell, Braxton D, Rao, Dabeeru C, Chen, Yii-Der Ida, Kardia, Sharon LR, Kaplan, Robert C, Mathias, Rasika A, He, Jiang, Psaty, Bruce M, Fornage, Myriam, Loos, Ruth JF, Correa, Adolfo, Boerwinkle, Eric, Rotter, Jerome I, Kooperberg, Charles, and Edwards, Todd L

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Human Genome, Genetics, 2.1 Biological and endogenous factors, Aetiology, Cardiovascular, Good Health and Well Being, Blood Pressure, Genome-Wide Association Study, Genomics, Humans, Hypertension, Polymorphism, Single Nucleotide, Precision Medicine, allele, blood pressure, genome, hypertension, whole genome sequencing, Samoan Obesity, Lifestyle, and Genetic Adaptations Study (OLaGA) Group, ‡ NHLBI Trans-Omics for Precision Medicine TOPMed) Consortium, Cardiorespiratory Medicine and Haematology, Public Health and Health Services, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences
Abstract

BackgroundThe availability of whole-genome sequencing data in large studies has enabled the assessment of coding and noncoding variants across the allele frequency spectrum for their associations with blood pressure.MethodsWe conducted a multiancestry whole-genome sequencing analysis of blood pressure among 51 456 Trans-Omics for Precision Medicine and Centers for Common Disease Genomics program participants (stage-1). Stage-2 analyses leveraged array data from UK Biobank (N=383 145), Million Veteran Program (N=318 891), and Reasons for Geographic and Racial Differences in Stroke (N=10 643) participants, along with whole-exome sequencing data from UK Biobank (N=199 631) participants.ResultsTwo blood pressure signals achieved genome-wide significance in meta-analyses of stage-1 and stage-2 single variant findings (P

Published
2022

6. Mendelian randomization supports bidirectional causality between telomere length and clonal hematopoiesis of indeterminate potential

Author

Nakao, Tetsushi, Bick, Alexander G, Taub, Margaret A, Zekavat, Seyedeh M, Uddin, Md M, Niroula, Abhishek, Carty, Cara L, Lane, John, Honigberg, Michael C, Weinstock, Joshua S, Pampana, Akhil, Gibson, Christopher J, Griffin, Gabriel K, Clarke, Shoa L, Bhattacharya, Romit, Assimes, Themistocles L, Emery, Leslie S, Stilp, Adrienne M, Wong, Quenna, Broome, Jai, Laurie, Cecelia A, Khan, Alyna T, Smith, Albert V, Blackwell, Thomas W, Codd, Veryan, Nelson, Christopher P, Yoneda, Zachary T, Peralta, Juan M, Bowden, Donald W, Irvin, Marguerite R, Boorgula, Meher, Zhao, Wei, Yanek, Lisa R, Wiggins, Kerri L, Hixson, James E, Gu, C Charles, Peloso, Gina M, Roden, Dan M, Reupena, Muagututi’a S, Hwu, Chii-Min, DeMeo, Dawn L, North, Kari E, Kelly, Shannon, Musani, Solomon K, Bis, Joshua C, Lloyd-Jones, Donald M, Johnsen, Jill M, Preuss, Michael, Tracy, Russell P, Peyser, Patricia A, Qiao, Dandi, Desai, Pinkal, Curran, Joanne E, Freedman, Barry I, Tiwari, Hemant K, Chavan, Sameer, Smith, Jennifer A, Smith, Nicholas L, Kelly, Tanika N, Hidalgo, Bertha, Cupples, L Adrienne, Weeks, Daniel E, Hawley, Nicola L, Minster, Ryan L, Deka, Ranjan, Naseri, Take T, de las Fuentes, Lisa, Raffield, Laura M, Morrison, Alanna C, Vries, Paul S, Ballantyne, Christie M, Kenny, Eimear E, Rich, Stephen S, Whitsel, Eric A, Cho, Michael H, Shoemaker, M Benjamin, Pace, Betty S, Blangero, John, Palmer, Nicholette D, Mitchell, Braxton D, Shuldiner, Alan R, Barnes, Kathleen C, Redline, Susan, Kardia, Sharon LR, Abecasis, Gonçalo R, Becker, Lewis C, Heckbert, Susan R, He, Jiang, Post, Wendy, Arnett, Donna K, Vasan, Ramachandran S, Darbar, Dawood, Weiss, Scott T, McGarvey, Stephen T, de Andrade, Mariza, Chen, Yii-Der Ida, Kaplan, Robert C, Meyers, Deborah A, Custer, Brian S, and Correa, Adolfo

Subjects
Cardiovascular, Genetics, Aging, Heart Disease, Heart Disease - Coronary Heart Disease, Human Genome, Atherosclerosis, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Samoan Obesity, Lifestyle and Genetic Adaptations Study (OLaGA) Group, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium
Abstract

Human genetic studies support an inverse causal relationship between leukocyte telomere length (LTL) and coronary artery disease (CAD), but directionally mixed effects for LTL and diverse malignancies. Clonal hematopoiesis of indeterminate potential (CHIP), characterized by expansion of hematopoietic cells bearing leukemogenic mutations, predisposes both hematologic malignancy and CAD. TERT (which encodes telomerase reverse transcriptase) is the most significantly associated germline locus for CHIP in genome-wide association studies. Here, we investigated the relationship between CHIP, LTL, and CAD in the Trans-Omics for Precision Medicine (TOPMed) program (n = 63,302) and UK Biobank (n = 47,080). Bidirectional Mendelian randomization studies were consistent with longer genetically imputed LTL increasing propensity to develop CHIP, but CHIP then, in turn, hastens to shorten measured LTL (mLTL). We also demonstrated evidence of modest mediation between CHIP and CAD by mLTL. Our data promote an understanding of potential causal relationships across CHIP and LTL toward prevention of CAD.

Published
2022

7. A genetic association study of circulating coagulation factor VIII and von Willebrand factor levels

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, Dan, 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, Becker, Julia Powers, Boorgula, Meher Preethi, 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, Hui-Heng Sheu, Wayne, 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 D., 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, Wilson, Carla, Wilson, James, Winterkorn, Lara, Wong, Quenna, 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, Lindstrom, Sara, Wang, Lu, Smith, Erin N., Gordon, William, van Hylckama Vlieg, Astrid, Brody, Jennifer A., Pattee, Jack W., Haessler, Jeffrey, Brumpton, Ben M., Chasman, Daniel I., Suchon, Pierre, Chen, Ming-Huei, Turman, Constance, Germain, Marine, Wiggins, Kerri L., MacDonald, James, Braekkan, Sigrid K., Armasu, Sebastian M., Pankratz, Nathan, 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, McKnight, Barbara, Kraft, Peter, Hansen, John-Bjarne, Rosendaal, Frits R., Heit, John A., Psaty, Bruce M., Tang, Weihong, Hveem, Kristian, Ridker, Paul M., Morange, Pierre-Emmanuel, Johnson, Andrew D., Kabrhel, Christopher, AlexandreTrégouët, David, Smith, Nicholas L., de Vries, Paul S., Reventun, Paula, Brown, Michael R., Heath, Adam S., Huffman, Jennifer E., Le, Ngoc-Quynh, Bebo, Allison, Temprano-Sagrera, Gerard, Raffield, Laura M., Ozel, Ayse Bilge, Thibord, Florian, Lewis, Joshua P., Rodriguez, Benjamin A. T., Polasek, Ozren, Yanek, Lisa R., Carrasquilla, German D., Marioni, Riccardo E., Kleber, Marcus E., Trégouët, David-Alexandre, Yao, Jie, Li-Gao, Ruifang, Joshi, Peter K., Trompet, Stella, Martinez-Perez, Angel, Ghanbari, Mohsen, Howard, Tom E., Reiner, Alex P., Arvanitis, Marios, Ryan, Kathleen A., Bartz, Traci M., Rudan, Igor, Faraday, Nauder, Linneberg, Allan, Davies, Gail, Delgado, Graciela E., Klaric, Lucija, Noordam, Raymond, van Rooij, Frank, Curran, Joanne E., Wheeler, Marsha M., Osburn, William O., O'Connell, Jeffrey R., Beswick, Andrew, Kolcic, Ivana, Souto, Juan Carlos, Becker, Lewis C., Hansen, Torben, Doyle, Margaret F., Harris, Sarah E., Moissl, Angela P., Rich, Stephen S., Campbell, Harry, Stott, David J., Soria, Jose Manuel, de Maat, Moniek P. M., Brody, Lawrence C., Auer, Paul L., Ben-Shlomo, Yoav, Hayward, Caroline, Mathias, Rasika A., Kilpeläinen, Tuomas O., Lange, Leslie A., Cox, Simon R., März, Winfried, Rotter, Jerome I., Mook-Kanamori, Dennis O., Wilson, James F., van der Harst, Pim, Jukema, J. Wouter, Ikram, M. Arfan, Desch, Karl C., Sabater-Lleal, Maria, Lowenstein, Charles J., and Morrison, Alanna C.

Published
2024
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8. 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
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9. Inherited causes of clonal haematopoiesis in 97,691 whole genomes

Author

Bick, Alexander G, Weinstock, Joshua S, Nandakumar, Satish K, Fulco, Charles P, Bao, Erik L, Zekavat, Seyedeh M, Szeto, Mindy D, Liao, Xiaotian, Leventhal, Matthew J, Nasser, Joseph, Chang, Kyle, Laurie, Cecelia, Burugula, Bala Bharathi, Gibson, Christopher J, Niroula, Abhishek, Lin, Amy E, Taub, Margaret A, Aguet, Francois, Ardlie, Kristin, Mitchell, Braxton D, Barnes, Kathleen C, Moscati, Arden, Fornage, Myriam, Redline, Susan, Psaty, Bruce M, Silverman, Edwin K, Weiss, Scott T, Palmer, Nicholette D, Vasan, Ramachandran S, Burchard, Esteban G, Kardia, Sharon LR, He, Jiang, Kaplan, Robert C, Smith, Nicholas L, Arnett, Donna K, Schwartz, David A, Correa, Adolfo, de Andrade, Mariza, Guo, Xiuqing, Konkle, Barbara A, Custer, Brian, Peralta, Juan M, Gui, Hongsheng, Meyers, Deborah A, McGarvey, Stephen T, Chen, Ida Yii-Der, Shoemaker, M Benjamin, Peyser, Patricia A, Broome, Jai G, Gogarten, Stephanie M, Wang, Fei Fei, Wong, Quenna, Montasser, May E, Daya, Michelle, Kenny, Eimear E, North, Kari E, Launer, Lenore J, Cade, Brian E, Bis, Joshua C, Cho, Michael H, Lasky-Su, Jessica, Bowden, Donald W, Cupples, L Adrienne, Mak, Angel CY, Becker, Lewis C, Smith, Jennifer A, Kelly, Tanika N, Aslibekyan, Stella, Heckbert, Susan R, Tiwari, Hemant K, Yang, Ivana V, Heit, John A, Lubitz, Steven A, Johnsen, Jill M, Curran, Joanne E, Wenzel, Sally E, Weeks, Daniel E, Rao, Dabeeru C, Darbar, Dawood, Moon, Jee-Young, Tracy, Russell P, Buth, Erin J, Rafaels, Nicholas, Loos, Ruth JF, Durda, Peter, Liu, Yongmei, Hou, Lifang, Lee, Jiwon, Kachroo, Priyadarshini, Freedman, Barry I, Levy, Daniel, Bielak, Lawrence F, Hixson, James E, Floyd, James S, Whitsel, Eric A, Ellinor, Patrick T, Irvin, Marguerite R, Fingerlin, Tasha E, Raffield, Laura M, and Armasu, Sebastian M

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Biotechnology, Regenerative Medicine, Stem Cell Research, Human Genome, Underpinning research, Aetiology, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors, Cardiovascular, Generic health relevance, Inflammatory and immune system, Good Health and Well Being, Adult, Africa, Aged, Aged, 80 and over, Black People, Cell Self Renewal, Clonal Hematopoiesis, DNA-Binding Proteins, Dioxygenases, Female, Genetic Predisposition to Disease, Genome, Human, Germ-Line Mutation, Hematopoietic Stem Cells, Humans, Intracellular Signaling Peptides and Proteins, Male, Middle Aged, National Heart, Lung, and Blood Institute (U.S.), Phenotype, Precision Medicine, Proto-Oncogene Proteins, Tripartite Motif Proteins, United States, Whole Genome Sequencing, alpha Karyopherins, NHLBI Trans-Omics for Precision Medicine Consortium, General Science & Technology
Abstract

Age is the dominant risk factor for most chronic human diseases, but the mechanisms through which ageing confers this risk are largely unknown1. The age-related acquisition of somatic mutations that lead to clonal expansion in regenerating haematopoietic stem cell populations has recently been associated with both haematological cancer2-4 and coronary heart disease5-this phenomenon is termed clonal haematopoiesis of indeterminate potential (CHIP)6. Simultaneous analyses of germline and somatic whole-genome sequences provide the opportunity to identify root causes of CHIP. Here we analyse high-coverage whole-genome sequences from 97,691 participants of diverse ancestries in the National Heart, Lung, and Blood Institute Trans-omics for Precision Medicine (TOPMed) programme, and identify 4,229 individuals with CHIP. We identify associations with blood cell, lipid and inflammatory traits that are specific to different CHIP driver genes. Association of a genome-wide set of germline genetic variants enabled the identification of three genetic loci associated with CHIP status, including one locus at TET2 that was specific to individuals of African ancestry. In silico-informed in vitro evaluation of the TET2 germline locus enabled the identification of a causal variant that disrupts a TET2 distal enhancer, resulting in increased self-renewal of haematopoietic stem cells. Overall, we observe that germline genetic variation shapes haematopoietic stem cell function, leading to CHIP through mechanisms that are specific to clonal haematopoiesis as well as shared mechanisms that lead to somatic mutations across tissues.

Published
2020

10. Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration.

Author

Noordam, Raymond, Bos, Maxime M, Wang, Heming, Winkler, Thomas W, Bentley, Amy R, Kilpeläinen, Tuomas O, de Vries, Paul S, Sung, Yun Ju, Schwander, Karen, Cade, Brian E, Manning, Alisa, Aschard, Hugues, Brown, Michael R, Chen, Han, Franceschini, Nora, Musani, Solomon K, Richard, Melissa, Vojinovic, Dina, Aslibekyan, Stella, Bartz, Traci M, de Las Fuentes, Lisa, Feitosa, Mary, Horimoto, Andrea R, Ilkov, Marjan, Kho, Minjung, Kraja, Aldi, Li, Changwei, Lim, Elise, Liu, Yongmei, Mook-Kanamori, Dennis O, Rankinen, Tuomo, Tajuddin, Salman M, van der Spek, Ashley, Wang, Zhe, Marten, Jonathan, Laville, Vincent, Alver, Maris, Evangelou, Evangelos, Graff, Maria E, He, Meian, Kühnel, Brigitte, Lyytikäinen, Leo-Pekka, Marques-Vidal, Pedro, Nolte, Ilja M, Palmer, Nicholette D, Rauramaa, Rainer, Shu, Xiao-Ou, Snieder, Harold, Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R, Adolfo, Correa, Ballantyne, Christie, Bielak, Larry, Biermasz, Nienke R, Boerwinkle, Eric, Dimou, Niki, Eiriksdottir, Gudny, Gao, Chuan, Gharib, Sina A, Gottlieb, Daniel J, Haba-Rubio, José, Harris, Tamara B, Heikkinen, Sami, Heinzer, Raphaël, Hixson, James E, Homuth, Georg, Ikram, M Arfan, Komulainen, Pirjo, Krieger, Jose E, Lee, Jiwon, Liu, Jingmin, Lohman, Kurt K, Luik, Annemarie I, Mägi, Reedik, Martin, Lisa W, Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Nalls, Mike A, O'Connell, Jeff, Peters, Annette, Peyser, Patricia, Raitakari, Olli T, Reiner, Alex P, Rensen, Patrick CN, Rice, Treva K, Rich, Stephen S, Roenneberg, Till, Rotter, Jerome I, Schreiner, Pamela J, Shikany, James, Sidney, Stephen S, Sims, Mario, Sitlani, Colleen M, Sofer, Tamar, Strauch, Konstantin, Swertz, Morris A, Taylor, Kent D, and Uitterlinden, André G

Subjects
Humans, Lipids, Chromosome Mapping, Sleep, Phylogeny, Polymorphism, Single Nucleotide, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Young Adult, Genetic Loci, Polymorphism, Single Nucleotide, and over
Abstract

Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To elucidate the biology of sleep-associated adverse lipid profile, we conduct multi-ancestry genome-wide sleep-SNP interaction analyses on three lipid traits (HDL-c, LDL-c and triglycerides). In the total study sample (discovery + replication) of 126,926 individuals from 5 different ancestry groups, when considering either long or short total sleep time interactions in joint analyses, we identify 49 previously unreported lipid loci, and 10 additional previously unreported lipid loci in a restricted sample of European-ancestry cohorts. In addition, we identify new gene-sleep interactions for known lipid loci such as LPL and PCSK9. The previously unreported lipid loci have a modest explained variance in lipid levels: most notable, gene-short-sleep interactions explain 4.25% of the variance in triglyceride level. Collectively, these findings contribute to our understanding of the biological mechanisms involved in sleep-associated adverse lipid profiles.

Published
2019

11. Genetically Determined Plasma Lipid Levels and Risk of Diabetic Retinopathy: A Mendelian Randomization Study

Author

Sobrin, Lucia, Chong, Yong He, Fan, Qiao, Gan, Alfred, Stanwyck, Lynn K, Kaidonis, Georgia, Craig, Jamie E, Kim, Jihye, Liao, Wen-Ling, Huang, Yu-Chuen, Lee, Wen-Jane, Hung, Yi-Jen, Guo, Xiuqing, Hai, Yang, Ipp, Eli, Pollack, Samuela, Hancock, Heather, Price, Alkes, Penman, Alan, Mitchell, Paul, Liew, Gerald, Smith, Albert V, Gudnason, Vilmundur, Tan, Gavin, Klein, Barbara EK, Kuo, Jane, Li, Xiaohui, Christiansen, Mark W, Psaty, Bruce M, Sandow, Kevin, Jensen, Richard A, Klein, Ronald, Cotch, Mary Frances, Wang, Jie Jin, Jia, Yucheng, Chen, Ching J, Chen, Yii-Der Ida, Rotter, Jerome I, Tsai, Fuu-Jen, Hanis, Craig L, Burdon, Kathryn P, Wong, Tien Yin, Cheng, Ching-Yu, Spracklen, Cassandra N, Chen, Peng, Kim, Young Jin, Wang, Xu, Cai, Hui, Li, Shengxu, Long, Jirong, Wu, Ying, Wang, Ya-Xing, Takeuchi, Fumihiko, Wu, Jer-Yuarn, Jung, Keum-Ji, Hu, Cheng, Akiyama, Koichi, Zhang, Yonghong, Moon, Sanghoon, Johnson, Todd A, Li, Huaixing, Dorajoo, Rajkumar, He, Meian, Cannon, Maren E, Roman, Tamara S, Salfati, Elias, Lin, Keng-Hung, Sheu, Wayne HH, Absher, Devin, Adair, Linda S, Assimes, Themistocles L, Aung, Tin, Cai, Qiuyin, Chang, Li-Ching, Chen, Chien-Hsiun, Chien, Li-Hsin, Chuang, Lee-Ming, Chuang, Shu-Chun, Du, Shufa, Fann, Cathy SJ, Feranil, Alan B, Friedlander, Yechiel, Gordon-Larsen, Penny, Gu, Dongfeng, Gui, Lixuan, Guo, Zhirong, Heng, Chew-Kiat, Hixson, James, Hou, Xuhong, Hsiung, Chao Agnes, Hu, Yao, Hwang, Mi Yeong, Hwu, Chii-Min, Isono, Masato, Juang, Jyh-Ming Jimmy, Khor, Chiea-Chuen, Kim, Yun Kyoung, Koh, Woon-Puay, Kubo, Michiaki, and Lee, I-Te

Subjects
Biomedical and Clinical Sciences, Cancer, Prevention, Eye Disease and Disorders of Vision, 2.1 Biological and endogenous factors, Aetiology, Metabolic and endocrine, Aged, Diabetic Retinopathy, Female, Genome-Wide Association Study, Humans, Lipids, Male, Mendelian Randomization Analysis, Middle Aged, Polymorphism, Single Nucleotide, Risk, Asian Genetic Epidemiology Network Consortium, Medical and Health Sciences, Endocrinology & Metabolism, Biomedical and clinical sciences
Abstract

Results from observational studies examining dyslipidemia as a risk factor for diabetic retinopathy (DR) have been inconsistent. We evaluated the causal relationship between plasma lipids and DR using a Mendelian randomization approach. We pooled genome-wide association studies summary statistics from 18 studies for two DR phenotypes: any DR (N = 2,969 case and 4,096 control subjects) and severe DR (N = 1,277 case and 3,980 control subjects). Previously identified lipid-associated single nucleotide polymorphisms served as instrumental variables. Meta-analysis to combine the Mendelian randomization estimates from different cohorts was conducted. There was no statistically significant change in odds ratios of having any DR or severe DR for any of the lipid fractions in the primary analysis that used single nucleotide polymorphisms that did not have a pleiotropic effect on another lipid fraction. Similarly, there was no significant association in the Caucasian and Chinese subgroup analyses. This study did not show evidence of a causal role of the four lipid fractions on DR. However, the study had limited power to detect odds ratios less than 1.23 per SD in genetically induced increase in plasma lipid levels, thus we cannot exclude that causal relationships with more modest effect sizes exist.

Published
2017

12. Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels

Author

Spracklen, Cassandra N, Chen, Peng, Kim, Young Jin, Wang, Xu, Cai, Hui, Li, Shengxu, Long, Jirong, Wu, Ying, Wang, Ya Xing, Takeuchi, Fumihiko, Wu, Jer-Yuarn, Jung, Keum-Ji, Hu, Cheng, Akiyama, Koichi, Zhang, Yonghong, Moon, Sanghoon, Johnson, Todd A, Li, Huaixing, Dorajoo, Rajkumar, He, Meian, Cannon, Maren E, Roman, Tamara S, Salfati, Elias, Lin, Keng-Hung, Guo, Xiuqing, Sheu, Wayne HH, Absher, Devin, Adair, Linda S, Assimes, Themistocles L, Aung, Tin, Cai, Qiuyin, Chang, Li-Ching, Chen, Chien-Hsiun, Chien, Li-Hsin, Chuang, Lee-Ming, Chuang, Shu-Chun, Du, Shufa, Fan, Qiao, Fann, Cathy SJ, Feranil, Alan B, Friedlander, Yechiel, Gordon-Larsen, Penny, Gu, Dongfeng, Gui, Lixuan, Guo, Zhirong, Heng, Chew-Kiat, Hixson, James, Hou, Xuhong, Hsiung, Chao Agnes, Hu, Yao, Hwang, Mi Yeong, Hwu, Chii-Min, Isono, Masato, Juang, Jyh-Ming Jimmy, Khor, Chiea-Chuen, Kim, Yun Kyoung, Koh, Woon-Puay, Kubo, Michiaki, Lee, I-Te, Lee, Sun-Ju, Lee, Wen-Jane, Liang, Kae-Woei, Lim, Blanche, Lim, Sing-Hui, Liu, Jianjun, Nabika, Toru, Pan, Wen-Harn, Peng, Hao, Quertermous, Thomas, Sabanayagam, Charumathi, Sandow, Kevin, Shi, Jinxiu, Sun, Liang, Tan, Pok Chien, Tan, Shu-Pei, Taylor, Kent D, Teo, Yik-Ying, Toh, Sue-Anne, Tsunoda, Tatsuhiko, van Dam, Rob M, Wang, Aili, Wang, Feijie, Wang, Jie, Bin Wei, Wen, Xiang, Yong-Bing, Yao, Jie, Yuan, Jian-Min, Zhang, Rong, Zhao, Wanting, Chen, Yii-Der Ida, Rich, Stephen S, Rotter, Jerome I, Wang, Tzung-Dau, Wu, Tangchun, Lin, Xu, Han, Bok-Ghee, Tanaka, Toshihiro, Cho, Yoon Shin, Katsuya, Tomohiro, and Jia, Weiping

Subjects
Genetics, Human Genome, Atherosclerosis, 2.1 Biological and endogenous factors, Aetiology, Metabolic and endocrine, Adult, Alleles, Asian People, Cholesterol, Ethnicity, Female, Gene Frequency, Genetic Association Studies, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Lipids, Lipoproteins, HDL, Lipoproteins, LDL, Male, Middle Aged, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Triglycerides, White People, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Large-scale meta-analyses of genome-wide association studies (GWAS) have identified >175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P

Published
2017

13. Genome-Wide Association Study Meta-Analysis of Long-Term Average Blood Pressure in East Asians

Author

Li, Changwei, Kim, Yun Kyoung, Dorajoo, Rajkumar, Li, Huaixing, Lee, I-Te, Cheng, Ching-Yu, He, Meian, Sheu, Wayne H-H, Guo, Xiuqing, Ganesh, Santhi K, He, Jiang, Lee, Juyoung, Liu, Jianjun, Hu, Yao, Rao, Dabeeru C, Tsai, Fuu-Jen, Koh, Jia Yu, Hu, Hua, Liang, Kae-Woei, Palmas, Walter, Hixson, James E, Han, Sohee, Teo, Yik-Ying, Wang, Yiqin, Chen, Jing, Lu, Chieh Hsiang, Zheng, Yingfeng, Gui, Lixuan, Lee, Wen-Jane, Yao, Jie, Gu, Dongfeng, Han, Bok-Ghee, Sim, Xueling, Sun, Liang, Zhao, Jinying, Chen, Chien-Hsiun, Kumari, Neelam, He, Yunfeng, Taylor, Kent D, Raffel, Leslie J, Moon, Sanghoon, Rotter, Jerome I, Ida Chen, Yii-der, Wu, Tangchun, Wong, Tien Yin, Wu, Jer-Yuarn, Lin, Xu, Tai, E-Shyong, Kim, Bong-Jo, and Kelly, Tanika N

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Biotechnology, Genetics, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Cardiovascular, Asian People, Blood Pressure, Asia, Eastern, Female, Genetic Loci, Genome-Wide Association Study, Humans, Male, Phenotype, Polymorphism, Single Nucleotide, arterial pressure, blood pressure, epidemiology, genome-wide association study, Medical Biotechnology, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

BackgroundGenome-wide single marker and gene-based meta-analyses of long-term average (LTA) blood pressure (BP) phenotypes may reveal novel findings for BP.Methods and resultsWe conducted genome-wide analysis among 18 422 East Asian participants (stage 1) followed by replication study of ≤46 629 participants of European ancestry (stage 2). Significant single-nucleotide polymorphisms and genes were determined by a P

Published
2017

14. Genome-wide association studies in East Asians identify new loci for waist-hip ratio and waist circumference.

Author

Wen, Wanqing, Kato, Norihiro, Hwang, Joo-Yeon, Guo, Xingyi, Tabara, Yasuharu, Li, Huaixing, Dorajoo, Rajkumar, Yang, Xiaobo, Tsai, Fuu-Jen, Li, Shengxu, Wu, Ying, Wu, Tangchun, Kim, Soriul, Guo, Xiuqing, Liang, Jun, Shungin, Dmitry, Adair, Linda S, Akiyama, Koichi, Allison, Matthew, Cai, Qiuyin, Chang, Li-Ching, Chen, Chien-Hsiun, Chen, Yuan-Tsong, Cho, Yoon Shin, Choi, Bo Youl, Gao, Yutang, Go, Min Jin, Gu, Dongfeng, Han, Bok-Ghee, He, Meian, Hixson, James E, Hu, Yanling, Huang, Tao, Isono, Masato, Jung, Keum Ji, Kang, Daehee, Kim, Young Jin, Kita, Yoshikuni, Lee, Juyoung, Lee, Nanette R, Lee, Jeannette, Wang, Yiqin, Liu, Jian-Jun, Long, Jirong, Moon, Sanghoon, Nakamura, Yasuyuki, Nakatochi, Masahiro, Ohnaka, Keizo, Rao, Dabeeru, Shi, Jiajun, Sull, Jae Woong, Tan, Aihua, Ueshima, Hirotsugu, Wu, Chen, Xiang, Yong-Bing, Yamamoto, Ken, Yao, Jie, Ye, Xingwang, Yokota, Mitsuhiro, Zhang, Xiaomin, Zheng, Yan, Qi, Lu, Rotter, Jerome I, Jee, Sun Ha, Lin, Dongxin, Mohlke, Karen L, He, Jiang, Mo, Zengnan, Wu, Jer-Yuarn, Tai, E Shyong, Lin, Xu, Miki, Tetsuro, Kim, Bong-Jo, Takeuchi, Fumihiko, Zheng, Wei, and Shu, Xiao-Ou

Subjects
Humans, Obesity, Genetic Predisposition to Disease, Waist-Hip Ratio, Sex Factors, Quantitative Trait, Heritable, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Asian Continental Ancestry Group, Asia, Female, Male, Waist Circumference, Genome-Wide Association Study, Quantitative Trait, Heritable, Polymorphism, Single Nucleotide, Clinical Research, Genetics, 2.1 Biological and endogenous factors, Cardiovascular, Biochemistry and Cell Biology, Other Physical Sciences
Abstract

Sixty genetic loci associated with abdominal obesity, measured by waist circumference (WC) and waist-hip ratio (WHR), have been previously identified, primarily from studies conducted in European-ancestry populations. We conducted a meta-analysis of associations of abdominal obesity with approximately 2.5 million single nucleotide polymorphisms (SNPs) among 53,052 (for WC) and 48,312 (for WHR) individuals of Asian descent, and replicated 33 selected SNPs among 3,762 to 17,110 additional individuals. We identified four novel loci near the EFEMP1, ADAMTSL3 , CNPY2, and GNAS genes that were associated with WC after adjustment for body mass index (BMI); two loci near the NID2 and HLA-DRB5 genes associated with WHR after adjustment for BMI, and three loci near the CEP120, TSC22D2, and SLC22A2 genes associated with WC without adjustment for BMI. Functional enrichment analyses revealed enrichment of corticotropin-releasing hormone signaling, GNRH signaling, and/or CDK5 signaling pathways for those newly-identified loci. Our study provides additional insight on genetic contribution to abdominal obesity.

Published
2016

15. Whole Genome Sequencing Identifies CRISPLD2 as a Lung Function Gene in Children With Asthma

Author

Abe, Namiko, Abecasis, Goncalo, Albert, Christine, Palmer Allred, Nicholette (Nichole), Almasy, Laura, Alonso, Alvaro, Ament, Seth, Anderson, Peter, Anugu, Pramod, Applebaum-Bowden, Deborah, Arking, Dan, Arnett, Donna K., Ashley-Koch, Allison, Aslibekyan, Stella, Assimes, Tim, Auer, Paul, Avramopoulos, Dimitrios, Barnard, John, Barnes, Kathleen, Barr, R. Graham, Barron-Casella, Emily, Beaty, Terri, Becker, Diane, Becker, Lewis, Beer, Rebecca, Begum, Ferdouse, Beitelshees, Amber, Benjamin, Emelia, Bezerra, Marcos, Bielak, Larry, Bis, Joshua, Blackwell, Thomas, Blangero, John, Boerwinkle, Eric, Borecki, Ingrid, Bowler, Russell, Brody, Jennifer, Broeckel, Ulrich, Broome, Jai, Bunting, Karen, Burchard, Esteban, Cardwell, Jonathan, Carty, Cara, Casaburi, Richard, Casella, James, Chaffin, Mark, Chang, Christy, Chasman, Daniel, Chavan, Sameer, Chen, Bo-Juen, Chen, Wei-Min, Chen, Yii-Der Ida, Cho, Michael H., Choi, Seung Hoan, Chuang, Lee-Ming, Chung, Mina, Cornell, Elaine, Correa, Adolfo, Crandall, Carolyn, Crapo, James, Cupples, L. Adrienne, Curran, Joanne, Curtis, Jeffrey, Custer, Brian, Damcott, Coleen, Darbar, Dawood, Das, Sayantan, David, Sean, Davis, Colleen, Daya, Michelle, de Andrade, Mariza, DeBaun, Michael, Deka, Ranjan, DeMeo, Dawn, Devine, Scott, Do, Ron, Duan, Qing, Duggirala, Ravi, Durda, Peter, Dutcher, Susan, Eaton, Charles, Ekunwe, Lynette, Ellinor, Patrick, Emery, Leslie, Farber, Charles, Farnam, Leanna, Fingerlin, Tasha, Flickinger, Matthew, Fornage, Myriam, Franceschini, Nora, Fu, Mao, Fullerton, Stephanie M., Fulton, Lucinda, Gabriel, Stacey, Gan, Weiniu, Gao, Yan, Gass, Margery, Gelb, Bruce, Geng, Xiaoqi (Priscilla), Germer, Soren, Gignoux, Chris, Gladwin, Mark, Glahn, David, Gogarten, Stephanie, Gong, Da-Wei, Goring, Harald, Gu, C. Charles, Guan, Yue, Guo, Xiuqing, Haessler, Jeff, Hall, Michael, Harris, Daniel, Hawley, Nicola, He, Jiang, Heavner, Ben, Heckbert, Susan, Hernandez, Ryan, Herrington, David, Hersh, Craig, Hidalgo, Bertha, Hixson, James, Hokanson, John, Holly, Kramer, Hong, Elliott, Hoth, Karin, (Agnes) Hsiung, Chao, Huston, Haley, Hwu, Chii Min, Irvin, Marguerite Ryan, Jackson, Rebecca, Jain, Deepti, Jaquish, Cashell, Jhun, Min A., Johnsen, Jill, Johnson, Andrew, Johnson, Craig, Johnston, Rich, Jones, Kimberly, Kachroo, Priyadarshini, Kang, Hyun Min, Kaplan, Robert, Kardia, Sharon, Kathiresan, Sekar, Kaufman, Laura, Kelly, Shannon, Kenny, Eimear, Kessler, Michael, Khan, Alyna, Kinney, Greg, Konkle, Barbara, Kooperberg, Charles, Krauter, Stephanie, Lange, Christoph, Lange, Ethan, Lange, Leslie, Laurie, Cathy, Laurie, Cecelia, LeBoff, Meryl, Lee, Seunggeun Shawn, Lee, Wen-Jane, LeFaive, Jonathon, Levine, David, Levy, Dan, Lewis, Joshua, Li, Yun, Lin, Honghuang, Lin, Keng Han, Liu, Simin, Liu, Yongmei, Loos, Ruth, Lubitz, Steven, Lunetta, Kathryn, Luo, James, Mahaney, Michael, Make, Barry, Manichaikul, Ani, Manson, JoAnn, Margolin, Lauren, Martin, Lisa, Mathai, Susan, Mathias, Rasika, McArdle, Patrick, McDonald, Merry-Lynn, McFarland, Sean, McGarvey, Stephen, Mei, Hao, Meyers, Deborah A., Mikulla, Julie, Min, Nancy, Minear, Mollie, Minster, Ryan L., Mitchell, Braxton, Montasser, May E., Musani, Solomon, Mwasongwe, Stanford, Mychaleckyj, Josyf C., Nadkarni, Girish, Naik, Rakhi, Natarajan, Pradeep, Nekhai, Sergei, Nickerson, Deborah, North, Kari, O'Connell, Jeff, O'Connor, Tim, Ochs-Balcom, Heather, Pankow, James, Papanicolaou, George, Parker, Margaret, Parsa, Afshin, Penchev, Sara, Peralta, Juan Manuel, Perez, Marco, Perry, James, Peters, Ulrike, Peyser, Patricia, Phillips, Lawrence S., Phillips, Sam, Pollin, Toni, Post, Wendy, Becker, Julia Powers, Boorgula, Meher Preethi, Preuss, Michael, Prokopenko, Dmitry, Psaty, Bruce, Qasba, Pankaj, Qiao, Dandi, Qin, Zhaohui, Rafaels, Nicholas, Raffield, Laura, Ramachandran, Vasan, Rao, D.C., Rasmussen-Torvik, Laura, Ratan, Aakrosh, Redline, Susan, Reed, Robert, Regan, Elizabeth, Reiner, Alex, Rice, Ken, Rich, Stephen, Roden, Dan, Roselli, Carolina, Rotter, Jerome, Ruczinski, Ingo, Russell, Pamela, Ruuska, Sarah, Ryan, Kathleen, Sakornsakolpat, Phuwanat, Salimi, Shabnam, Salzberg, Steven, Sandow, Kevin, Sankaran, Vijay, Scheller, Christopher, Schmidt, Ellen, Schwander, Karen, Schwartz, David, Sciurba, Frank, Seidman, Christine, Seidman, Jonathan, Sheehan, Vivien, Shetty, Amol, Shetty, Aniket, Sheu, Wayne Hui-Heng, Shoemaker, M. Benjamin, Silver, Brian, Silverman, Edwin, Smith, Jennifer, Smith, Josh, Smith, Nicholas, Smith, Tanja, Smoller, Sylvia, Snively, Beverly, Sofer, Tamar, Sotoodehnia, Nona, Stilp, Adrienne, Streeten, Elizabeth, Sung, Yun Ju, Su-Lasky, Jessica, Sylvia, Jody, Szpiro, Adam, Sztalryd, Carole, Taliun, Daniel, Tang, Hua, Taub, Margaret, Taylor, Kent, Taylor, Simeon, Telen, Marilyn, Thornton, Timothy A., Tinker, Lesley, Tirschwell, David, Tiwari, Hemant, Tracy, Russell, Tsai, Michael, Vaidya, Dhananjay, VandeHaar, Peter, Vrieze, Scott, Walker, Tarik, Wallace, Robert, Walts, Avram, Wan, Emily, Wang, Fei Fei, Watson, Karol, Weeks, Daniel E., Weir, Bruce, Weiss, Scott, Weng, Lu-Chen, Willer, Cristen, Williams, Kayleen, Williams, L. Keoki, Wilson, Carla, Wilson, James, Wong, Quenna, Xu, Huichun, Yanek, Lisa, Yang, Ivana, Yang, Rongze, Zaghloul, Norann, Zekavat, Maryam, Zhang, Yingze, Zhao, Snow Xueyan, Zhao, Wei, Zheng, Xiuwen, Zhi, Degui, Zhou, Xiang, Zody, Michael, Zoellner, Sebastian, Hecker, Julian, Chawes, Bo L., Ahluwalia, Tarunveer S., Kelly, Rachel S., Chu, Su H., Virkud, Yamini V., Huang, Mengna, Barnes, Kathleen C., Burchard, Esteban G., Eng, Celeste, Hu, Donglei, Celedón, Juan C., Levin, Albert M., Gui, Hongsheng, Forno, Erick, Mak, Angel C.Y., Avila, Lydiana, Soto-Quiros, Manuel E., Cloutier, Michelle M., Acosta-Pérez, Edna, Canino, Glorisa, Bønnelykke, Klaus, Bisgaard, Hans, Raby, Benjamin A., Weiss, Scott T., and Lasky-Su, Jessica A.

Published
2019
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16. Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index

Author

Wen, Wanqing, Zheng, Wei, Okada, Yukinori, Takeuchi, Fumihiko, Tabara, Yasuharu, Hwang, Joo-Yeon, Dorajoo, Rajkumar, Li, Huaixing, Tsai, Fuu-Jen, Yang, Xiaobo, He, Jiang, Wu, Ying, He, Meian, Zhang, Yi, Liang, Jun, Guo, Xiuqing, Sheu, Wayne Huey-Herng, Delahanty, Ryan, Guo, Xingyi, Kubo, Michiaki, Yamamoto, Ken, Ohkubo, Takayoshi, Go, Min Jin, Liu, Jian Jun, Gan, Wei, Chen, Ching-Chu, Gao, Yong, Li, Shengxu, Lee, Nanette R, Wu, Chen, Zhou, Xueya, Song, Huaidong, Yao, Jie, Lee, I-Te, Long, Jirong, Tsunoda, Tatsuhiko, Akiyama, Koichi, Takashima, Naoyuki, Cho, Yoon Shin, Ong, Rick TH, Lu, Ling, Chen, Chien-Hsiun, Tan, Aihua, Rice, Treva K, Adair, Linda S, Gui, Lixuan, Allison, Matthew, Lee, Wen-Jane, Cai, Qiuyin, Isomura, Minoru, Umemura, Satoshi, Kim, Young Jin, Seielstad, Mark, Hixson, James, Xiang, Yong-Bing, Isono, Masato, Kim, Bong-Jo, Sim, Xueling, Lu, Wei, Nabika, Toru, Lee, Juyoung, Lim, Wei-Yen, Gao, Yu-Tang, Takayanagi, Ryoichi, Kang, Dae-Hee, Wong, Tien Yin, Hsiung, Chao Agnes, Wu, I-Chien, Juang, Jyh-Ming Jimmy, Shi, Jiajun, Choi, Bo Youl, Aung, Tin, Hu, Frank, Kim, Mi Kyung, Lim, Wei Yen, Wang, Tzung-Dao, Shin, Min-Ho, Lee, Jeannette, Ji, Bu-Tian, Lee, Young-Hoon, Young, Terri L, Shin, Dong Hoon, Chun, Byung-Yeol, Cho, Myeong-Chan, Han, Bok-Ghee, Hwu, Chii-Min, Assimes, Themistocles L, Absher, Devin, Yan, Xiaofei, Kim, Eric, Kuo, Jane Z, Kwon, Soonil, Taylor, Kent D, Chen, Yii-Der I, Rotter, Jerome I, Qi, Lu, Zhu, Dingliang, Wu, Tangchun, Mohlke, Karen L, and Gu, Dongfeng

Subjects
Biological Sciences, Genetics, Obesity, Nutrition, Human Genome, Women's Health, 5'-Nucleotidase, Aldehyde Dehydrogenase, Aldehyde Dehydrogenase, Mitochondrial, Asian People, Blood Proteins, Body Mass Index, Cardiac Myosins, Asia, Eastern, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Glycoproteins, Humans, KCNQ1 Potassium Channel, Male, Myosin Light Chains, Polymorphism, Single Nucleotide, Proteinase Inhibitory Proteins, Secretory, Medical and Health Sciences, Genetics & Heredity
Abstract

Recent genetic association studies have identified 55 genetic loci associated with obesity or body mass index (BMI). The vast majority, 51 loci, however, were identified in European-ancestry populations. We conducted a meta-analysis of associations between BMI and ∼2.5 million genotyped or imputed single nucleotide polymorphisms among 86 757 individuals of Asian ancestry, followed by in silico and de novo replication among 7488-47 352 additional Asian-ancestry individuals. We identified four novel BMI-associated loci near the KCNQ1 (rs2237892, P = 9.29 × 10(-13)), ALDH2/MYL2 (rs671, P = 3.40 × 10(-11); rs12229654, P = 4.56 × 10(-9)), ITIH4 (rs2535633, P = 1.77 × 10(-10)) and NT5C2 (rs11191580, P = 3.83 × 10(-8)) genes. The association of BMI with rs2237892, rs671 and rs12229654 was significantly stronger among men than among women. Of the 51 BMI-associated loci initially identified in European-ancestry populations, we confirmed eight loci at the genome-wide significance level (P < 5.0 × 10(-8)) and an additional 14 at P < 1.0 × 10(-3) with the same direction of effect as reported previously. Findings from this analysis expand our knowledge of the genetic basis of obesity.

Published
2014

17. 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
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19. Meta-analysis identifies multiple loci associated with kidney function–related traits in east Asian populations

Author

Okada, Yukinori, Sim, Xueling, Go, Min Jin, Wu, Jer-Yuarn, Gu, Dongfeng, Takeuchi, Fumihiko, Takahashi, Atsushi, Maeda, Shiro, Tsunoda, Tatsuhiko, Chen, Peng, Lim, Su-Chi, Wong, Tien-Yin, Liu, Jianjun, Young, Terri L, Aung, Tin, Seielstad, Mark, Teo, Yik-Ying, Kim, Young Jin, Lee, Jong-Young, Han, Bok-Ghee, Kang, Daehee, Chen, Chien-Hsiun, Tsai, Fuu-Jen, Chang, Li-Ching, Fann, S-J Cathy, Mei, Hao, Rao, Dabeeru C, Hixson, James E, Chen, Shufeng, Katsuya, Tomohiro, Isono, Masato, Ogihara, Toshio, Chambers, John C, Zhang, Weihua, Kooner, Jaspal S, Albrecht, Eva, Yamamoto, Kazuhiko, Kubo, Michiaki, Nakamura, Yusuke, Kamatani, Naoyuki, Kato, Norihiro, He, Jiang, Chen, Yuan-Tsong, Cho, Yoon Shin, Tai, E-Shyong, and Tanaka, Toshihiro

Subjects
Biological Sciences, Genetics, Kidney Disease, Human Genome, Renal and urogenital, Asian People, Blood Urea Nitrogen, Cohort Studies, Creatinine, Genetic Predisposition to Disease, Genome-Wide Association Study, Glomerular Filtration Rate, Humans, Kidney, Polymorphism, Single Nucleotide, Renal Insufficiency, Chronic, Uric Acid, KidneyGen Consortium, CKDGen Consortium, GUGC consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Chronic kidney disease (CKD), impairment of kidney function, is a serious public health problem, and the assessment of genetic factors influencing kidney function has substantial clinical relevance. Here, we report a meta-analysis of genome-wide association studies for kidney function-related traits, including 71,149 east Asian individuals from 18 studies in 11 population-, hospital- or family-based cohorts, conducted as part of the Asian Genetic Epidemiology Network (AGEN). Our meta-analysis identified 17 loci newly associated with kidney function-related traits, including the concentrations of blood urea nitrogen, uric acid and serum creatinine and estimated glomerular filtration rate based on serum creatinine levels (eGFRcrea) (P < 5.0 × 10(-8)). We further examined these loci with in silico replication in individuals of European ancestry from the KidneyGen, CKDGen and GUGC consortia, including a combined total of ∼110,347 individuals. We identify pleiotropic associations among these loci with kidney function-related traits and risk of CKD. These findings provide new insights into the genetics of kidney function.

Published
2012

21. Assessment of postprandial triglycerides in clinical practice: Validation in a general population and coronary heart disease patients

Author

Perez-Martinez, Pablo, Alcala-Diaz, Juan F., Kabagambe, Edmon K., Garcia-Rios, Antonio, Tsai, Michael Y., Delgado-Lista, Javier, Kolovou, Genovefa, Straka, Robert J., Gomez-Delgado, Francisco, Hopkins, Paul N., Marin, Carmen, Borecki, Ingrid, Yubero-Serrano, Elena M., Hixson, James E., Camargo, Antonio, Province, Michael A., Lopez-Moreno, Javier, Rodriguez-Cantalejo, Fernando, Tinahones, Francisco J., Mikhailidis, Dimitri P., Perez-Jimenez, Francisco, Arnett, Donna K., Ordovas, Jose M., and Lopez-Miranda, Jose

Published
2016
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22. An APOO Pseudogene on Chromosome 5q Is Associated With Low-Density Lipoprotein Cholesterol Levels

Author

Montasser, May E., O’Hare, Elizabeth A., Wang, Xiaochun, Howard, Alicia D., McFarland, Rebecca, Perry, James A., Ryan, Kathleen A., Rice, Kenneth, Jaquish, Cashell E., Shuldiner, Alan R., Miller, Michael, Mitchell, Braxton D., Zaghloul, Norann A., Chang, Yen-Pei C., Abe, Namiko, Abecasis, Goncalo, Albert, Christine, Allred, Nicholette P., Almasy, Laura, Alonso, Alvaro, Ament, Seth, Anderson, Peter, Anugu, Pramod, Applebaum-Bowden, Debora, Arking, Dan, Arnett, Donna K, Ashley-Koch, Allison, Aslibekyan, Stella, Assimes, Tim, Auer, Paul, Avramopoulos, Dimitrios, Barnard, John, Barnes, Kathleen, Graham Barr, R., Barron-Casella, Emily, Beaty, Terri, Becker, Diane, Becker, Lewis, Beer, Rebecca, Begum, Ferdouse, Beitelshees, Amber, Benjamin, Emelia, Bezerra, Marcos, Bielak, Larry, Bis, Joshua, Blackwell, Thomas, Blangero, John, Boerwinkle, Eric, Borecki, Ingrid, Bowler, Russel, Brody, Jennifer, Broeckel, Ulrich, Broome, Jai, Bunting, Karen, Burchard, Esteban, Cardwell, Jonathan, Carlson, Sara, Carty, Cara, Casaburi, Richard, Casella, James, Chaffin, Mark, Chang, Christy, Chasman, Daniel, Chavan, Sameer, Chen, Bo-Juen, Chen, Wei-Min, Ida Chen, Yii-Der, Cho, Michael, Choi, Seung Hoan, Chuang, Lee-Ming, Chung, Mina, Cornell, Elaine, Correa, Adolfo, Crandall, Carolyn, Crapo, James, Cupples, L Adrienne, Curran, Joanne, Curtis, Jeffrey, Custer, Brian, Damcott, Coleen, Darbar, Dawood, Das, Sayantan, David, Sean, Davis, Colleen, Daya, Michelle, de Andrade, Mariza, DeBaun, Michael, Deka, Ranjan, DeMeo, Dawn, Devine, Scott, Do, Ron, Duan, Qing, Duggirala, Ravi, Durda, Peter, Dutcher, Susan, Eaton, Charles, Ekunwe, Lynette, Ellinor, Patrick, Emery, Leslie, Farber, Charles, Farnam, Leanna, Fingerlin, Tasha, Flickinger, Matthew, Fornage, Myriam, Franceschini, Nora, Fu, Mao, Fullerton, Malia, Fulton, Lucinda, Gabriel, Stacey, Gan, Weiniu, Gao, Yan, Gass, Margery, Gelb, Bruce, Geng, Xiaoqi (Priscilla), Germer, Soren, Gignoux, Chris, Gladwin, Mark, Glahn, David, Gogarten, Stephanie, Gong, Da-Wei, Goring, Harald, Charles Gu, C., Guan, Yue, Guo, Xiuqing, Haessler, Jeff, Hall, Michael, Harris, Daniel, Hawley, Nicola, He, Jiang, Heavner, Ben, Heckbert, Susan, Hernandez, Ryan, Herrington, David, Hersh, Craig, Hidalgo, Bertha, Hixson, James, Hokanson, John, Hong, Elliott, Hoth, Karin, Hsiung, Chao (Agnes), Huston, Haley, Hwu, Chii Min, Irvin, Marguerite, Jackson, Rebecca, Jain, Deepti, Jaquish, Cashell, Jhun, Min A, Johnsen, Jill, Johnson, Andrew, Johnson, Craig, Johnston, Rich, Jones, Kimberly, Kang, Hyun Min, Kaplan, Robert, Kardia, Sharon, Kathiresan, Sekar, Kaufman, Laura, Kelly, Shannon, Kenny, Eimear, Kessler, Michael, Khan, Alyna, Kinney, Greg, Konkle, Barbara, Kooperberg, Charles, Kramer, Holly, Krauter, Stephanie, Lange, Christoph, Lange, Ethan, Lange, Leslie, Laurie, Cathy, Laurie, Cecelia, LeBoff, Meryl, Lee, Seunggeun, Lee, Wen-Jane, LeFaive, Jonathon, Levine, David, Levy, Dan, Lewis, Joshua, Li, Yun, Lin, Honghuang, Lin, Keng Han, Liu, Simin, Liu, Yongmei, Loos, Ruth, Lunetta, Kathryn, Luo, James, Mahaney, Michael, Make, Barry, Manichaikul, Ani, Manson, JoAnn, Margolin, Lauren, Martin, Lisa, Mathai, Susan, Mathias, Rasika, McArdle, Patrick, McDonald, Merry-Lynn, McFarland, Sean, McGarvey, Stephen, Mei, Hao, Meyers, Deborah, Mikulla, Julie, Min, Nancy, Minear, Mollie, Minster, Ryan L, Mitchell, Braxton, Musani, Solomon, Mwasongwe, Stanford, Mychaleckyj, Josyf C, Nadkarni, Girish, Naik, Rakhi Johns, Natarajan, Pradeep, Nekhai, Sergei, Nickerson, Deborah, North, Kari, O’Connell, Jeff, O’Connor, Tim, Heather, Ochs-Balcom, Pankow, James, Papanicolaou, George, Parker, Margaret, Parsa, Afshin, Pattison, Jessica Tangarone, Penchev, Sara, Peralta, Juan Manuel, Perez, Marco, Perry, James, Peters, Ulrike, Peyser, Patricia, Phillips, Larry, Phillips, Sam, Pollin, Toni, Post, Wendy, Becker, Julia Powers, Boorgula, Meher Preethi, Preuss, Michael, Prokopenko, Dmitry, Psaty, Bruce, Qasba, Pankaj, Qiao, Dandi, Qin, Zhaohui, Rafaels, Nicholas, Raffield, Laura, Ramachandran, Vasan, Rao, D.C., Rasmussen-Torvik, Laura, Ratan, Aakrosh, Redline, Susan, Reed, Robert, Regan, Elizabeth, Reiner, Alex, Rice, Ken, Rich, Stephen, Roden, Dan, Roselli, Carolina, Rotter, Jerome, Ruczinski, Ingo, Russell, Pamela, Ruuska, Sarah, Ryan, Kathleen, Sakornsakolpat, Phuwanat, Salimi, Shabnam, Salzberg, Steven, Sandow, Kevin, Sankaran, Vijay, Scheller, Christopher, Schmidt, Ellen, Schwander, Karen, Schwartz, David, Sciurba, Frank, Seidman, Christine, Sheehan, Vivien, Shetty, Amol, Shetty, Aniket, Hui-Heng Sheu, Wayne, Benjamin Shoemaker, M., Silver, Brian, Silverman, Edwin, Smith, Jennifer, Smith, Josh, Smith, Nicholas, Smith, Tanja, Smoller, Sylvia, Snively, Beverly, Sofer, Tamar, Sotoodehnia, Nona, Stilp, Adrienne, Streeten, Elizabeth, Sung, Yun Ju, Sylvia, Jody, Szpiro, Adam, Sztalryd, Carole, Taliun, Daniel, Tang, Hua, Taub, Margaret, Taylor, Kent, Taylor, Simeon, Telen, Marilyn, Thornton, Timothy A., Tinker, Lesley, Tirschwell, David, Tiwari, Hemant, Tracy, Russell, Tsai, Michael, Vaidya, Dhananjay, VandeHaar, Peter, Vrieze, Scott, Walker, Tarik, Wallace, Robert, Walts, Avram, Wan, Emily, Fei Wang, Fei, Watson, Karol, Weeks, Daniel E., Weir, Bruce, Weiss, Scott, Weng, Lu-Chen, Willer, Cristen, Williams, Kayleen, Keoki Williams, L., Wilson, Carla, Wilson, James, Wong, Quenna, Xu, Huichun, Yanek, Lisa, Yang, Ivana, Yang, Rongze, Zaghloul, Norann, Zhang, Yingze, Zhao, Snow Xueyan, Zhao, Wei, Zheng, Xiuwen, Zhi, Degui, Zhou, Xiang, Zody, Michael, and Zoellner, Sebastian

Published
2018
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23. Proteomic Architecture of Human Coronary and Aortic Atherosclerosis

Author

Herrington, David M., Mao, Chunhong, Parker, Sarah J., Fu, Zongming, Yu, Guoqiang, Chen, Lulu, Venkatraman, Vidya, Fu, Yi, Wang, Yizhi, Howard, Timothy D., Jun, Goo, Zhao, Caroline F., Liu, Yongmei, Saylor, Georgia, Spivia, Weston R., Athas, Grace B., Troxclair, Dana, Hixson, James E., Vander Heide, Richard S., Wang, Yue, and Van Eyk, Jennifer E.

Published
2018
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26. Insights From a Large-Scale Whole-Genome Sequencing Study of Systolic Blood Pressure, Diastolic Blood Pressure, and Hypertension.

Author

Kelly, Tanika, Kelly, Tanika, Sun, Xiao, He, Karen, Brown, Michael, Taliun, Sarah, Hellwege, Jacklyn, Irvin, Marguerite, Mi, Xuenan, Brody, Jennifer, Franceschini, Nora, Guo, Xiuqing, Hwang, Shih-Jen, de Vries, Paul, Gao, Yan, Moscati, Arden, Nadkarni, Girish, Yanek, Lisa, Elfassy, Tali, Smith, Jennifer, Chung, Ren-Hua, Beitelshees, Amber, Patki, Amit, Aslibekyan, Stella, Blobner, Brandon, Peralta, Juan, Assimes, Themistocles, Palmas, Walter, Liu, Chunyu, Bress, Adam, Huang, Zhijie, Becker, Lewis, Hwa, Chii-Min, OConnell, Jeffrey, Carlson, Jenna, Warren, Helen, Das, Sayantan, Giri, Ayush, Martin, Lisa, Craig Johnson, W, Fox, Ervin, Bottinger, Erwin, Razavi, Alexander, Vaidya, Dhananjay, Chuang, Lee-Ming, Chang, Yen-Pei, Naseri, Take, Jain, Deepti, Kang, Hyun, Hung, Adriana, Srinivasasainagendra, Vinodh, Snively, Beverly, Gu, Dongfeng, Montasser, May, Reupena, Muagututia, Heavner, Benjamin, LeFaive, Jonathon, Hixson, James, Rice, Kenneth, Wang, Fei, Nielsen, Jonas, Huang, Jianfeng, Khan, Alyna, Zhou, Wei, Nierenberg, Jovia, Laurie, Cathy, Armstrong, Nicole, Shi, Mengyao, Pan, Yang, Stilp, Adrienne, Emery, Leslie, Wong, Quenna, Hawley, Nicola, Minster, Ryan, Curran, Joanne, Munroe, Patricia, Weeks, Daniel, North, Kari, Tracy, Russell, Kenny, Eimear, Shimbo, Daichi, Chakravarti, Aravinda, Rich, Stephen, Reiner, Alex, Blangero, John, Redline, Susan, Mitchell, Braxton, Rao, Dabeeru, Ida Chen, Yii-Der, Kardia, Sharon, Kaplan, Robert, Mathias, Rasika, He, Jiang, Psaty, Bruce, Fornage, Myriam, Loos, Ruth, Correa, Adolfo, Boerwinkle, Eric, Kooperberg, Charles, Edwards, Todd, Kelly, Tanika, Kelly, Tanika, Sun, Xiao, He, Karen, Brown, Michael, Taliun, Sarah, Hellwege, Jacklyn, Irvin, Marguerite, Mi, Xuenan, Brody, Jennifer, Franceschini, Nora, Guo, Xiuqing, Hwang, Shih-Jen, de Vries, Paul, Gao, Yan, Moscati, Arden, Nadkarni, Girish, Yanek, Lisa, Elfassy, Tali, Smith, Jennifer, Chung, Ren-Hua, Beitelshees, Amber, Patki, Amit, Aslibekyan, Stella, Blobner, Brandon, Peralta, Juan, Assimes, Themistocles, Palmas, Walter, Liu, Chunyu, Bress, Adam, Huang, Zhijie, Becker, Lewis, Hwa, Chii-Min, OConnell, Jeffrey, Carlson, Jenna, Warren, Helen, Das, Sayantan, Giri, Ayush, Martin, Lisa, Craig Johnson, W, Fox, Ervin, Bottinger, Erwin, Razavi, Alexander, Vaidya, Dhananjay, Chuang, Lee-Ming, Chang, Yen-Pei, Naseri, Take, Jain, Deepti, Kang, Hyun, Hung, Adriana, Srinivasasainagendra, Vinodh, Snively, Beverly, Gu, Dongfeng, Montasser, May, Reupena, Muagututia, Heavner, Benjamin, LeFaive, Jonathon, Hixson, James, Rice, Kenneth, Wang, Fei, Nielsen, Jonas, Huang, Jianfeng, Khan, Alyna, Zhou, Wei, Nierenberg, Jovia, Laurie, Cathy, Armstrong, Nicole, Shi, Mengyao, Pan, Yang, Stilp, Adrienne, Emery, Leslie, Wong, Quenna, Hawley, Nicola, Minster, Ryan, Curran, Joanne, Munroe, Patricia, Weeks, Daniel, North, Kari, Tracy, Russell, Kenny, Eimear, Shimbo, Daichi, Chakravarti, Aravinda, Rich, Stephen, Reiner, Alex, Blangero, John, Redline, Susan, Mitchell, Braxton, Rao, Dabeeru, Ida Chen, Yii-Der, Kardia, Sharon, Kaplan, Robert, Mathias, Rasika, He, Jiang, Psaty, Bruce, Fornage, Myriam, Loos, Ruth, Correa, Adolfo, Boerwinkle, Eric, Kooperberg, Charles, and Edwards, Todd

Abstract

BACKGROUND: The availability of whole-genome sequencing data in large studies has enabled the assessment of coding and noncoding variants across the allele frequency spectrum for their associations with blood pressure. METHODS: We conducted a multiancestry whole-genome sequencing analysis of blood pressure among 51 456 Trans-Omics for Precision Medicine and Centers for Common Disease Genomics program participants (stage-1). Stage-2 analyses leveraged array data from UK Biobank (N=383 145), Million Veteran Program (N=318 891), and Reasons for Geographic and Racial Differences in Stroke (N=10 643) participants, along with whole-exome sequencing data from UK Biobank (N=199 631) participants. RESULTS: Two blood pressure signals achieved genome-wide significance in meta-analyses of stage-1 and stage-2 single variant findings (P<5×10-8). Among them, a rare intergenic variant at novel locus, LOC100506274, was associated with lower systolic blood pressure in stage-1 (beta [SE]=-32.6 [6.0]; P=4.99×10-8) but not stage-2 analysis (P=0.11). Furthermore, a novel common variant at the known INSR locus was suggestively associated with diastolic blood pressure in stage-1 (beta [SE]=-0.36 [0.07]; P=4.18×10-7) and attained genome-wide significance in stage-2 (beta [SE]=-0.29 [0.03]; P=7.28×10-23). Nineteen additional signals suggestively associated with blood pressure in meta-analysis of single and aggregate rare variant findings (P<1×10-6 and P<1×10-4, respectively). DISCUSSION: We report one promising but unconfirmed rare variant for blood pressure and, more importantly, contribute insights for future blood pressure sequencing studies. Our findings suggest promise of aggregate analyses to complement single variant analysis strategies and the need for larger, diverse samples, and family studies to enable robust rare variant identification.

Published
2022

29. Whole Genome Sequence Analysis of the Plasma Proteome in Black Adults Provides Novel Insights Into Cardiovascular Disease

Author

Katz, Daniel H., primary, Tahir, Usman A., additional, Bick, Alexander G., additional, Pampana, Akhil, additional, Ngo, Debby, additional, Benson, Mark D., additional, Yu, Zhi, additional, Robbins, Jeremy M., additional, Chen, Zsu-Zsu, additional, Cruz, Daniel E., additional, Deng, Shuliang, additional, Farrell, Laurie, additional, Sinha, Sumita, additional, Schmaier, Alec A., additional, Shen, Dongxiao, additional, Gao, Yan, additional, Hall, Michael E., additional, Correa, Adolfo, additional, Tracy, Russell P., additional, Durda, Peter, additional, Taylor, Kent D., additional, Liu, Yongmei, additional, Johnson, W. Craig, additional, Guo, Xiuqing, additional, Yao, Jie, additional, Ida Chen, Yii-Der, additional, Manichaikul, Ani W., additional, Jain, Deepti, additional, Bouchard, Claude, additional, Sarzynski, Mark A., additional, Rich, Stephen S., additional, Rotter, Jerome I., additional, Wang, Thomas J., additional, Wilson, James G., additional, Natarajan, Pradeep, additional, Gerszten, Robert E., 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, 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, 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, Chen, Yii-Der Ida, 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, 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, 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, Gupta, Namrata, additional, Haas, David M., 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, 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, Levy, Dan, additional, Lewis, Joshua, additional, Li, Xiaohui, additional, Li, Yun, additional, Lin, Henry, additional, Lin, Honghuang, additional, Lin, Xihong, additional, Liu, Simin, 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, 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, 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, Van Den Berg, David, 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, Weiss, Scott T., additional, Weng, Lu-Chen, additional, Wessel, Jennifer, additional, Willer, Cristen, additional, Williams, Kayleen, additional, Williams, L. Keoki, additional, Wilson, Carla, additional, Wilson, James, additional, Winterkorn, Lara, additional, Wong, Quenna, 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, Zody, Michael, additional, and Zoellner, Sebastian, additional

Published
2022
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35. Genome-wide association study in Chinese identifies novel loci for blood pressure and hypertension

Author

Lu, Xiangfeng, Wang, Laiyuan, Lin, Xu, Huang, Jianfeng, Charles Gu, C., He, Meian, Shen, Hongbing, He, Jiang, Zhu, Jingwen, Li, Huaixing, Hixson, James E., Wu, Tangchun, Dai, Juncheng, Lu, Ling, Shen, Chong, Chen, Shufeng, He, Lin, Mo, Zengnan, Hao, Yongchen, Mo, Xingbo, Yang, Xueli, Li, Jianxin, Cao, Jie, Chen, Jichun, Fan, Zhongjie, Li, Ying, Zhao, Liancheng, Li, Hongfan, Lu, Fanghong, Yao, Cailiang, Yu, Lin, Xu, Lihua, Mu, Jianjun, Wu, Xianping, Deng, Ying, Hu, Dongsheng, Zhang, Weidong, Ji, Xu, Guo, Dongshuang, Guo, Zhirong, Zhou, Zhengyuan, Yang, Zili, Wang, Renping, Yang, Jun, Zhou, Xiaoyang, Yan, Weili, Sun, Ningling, Gao, Pingjin, and Gu, Dongfeng

Published
2015
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36. Genome-Wide Association Meta-analysis Identifies Novel Variants Associated With Fasting Plasma Glucose in East Asians

Author

Hwang, Joo-Yeon, Sim, Xueling, Wu, Ying, Liang, Jun, Tabara, Yasuharu, Hu, Cheng, Hara, Kazuo, Tam, Claudia H.T., Cai, Qiuyin, Zhao, Qi, Jee, Sunha, Takeuchi, Fumihiko, Go, Min Jin, Ong, Rick Twee Hee, Ohkubo, Takayoshi, Kim, Young Jin, Zhang, Rong, Yamauchi, Toshimasa, So, Wing Yee, Long, Jirong, Gu, Dongfeng, Lee, Nanette R., Kim, Soriul, Katsuya, Tomohiro, Oh, Ji Hee, Liu, Jianjun, Umemura, Satoshi, Kim, Yeon-Jung, Jiang, Feng, Maeda, Shiro, Chan, Juliana C.N., Lu, Wei, Hixson, James E., Adair, Linda S., Jung, Keum Ji, Nabika, Toru, Bae, Jae-Bum, Lee, Mi Hee, Seielstad, Mark, Young, Terri L., Teo, Yik Ying, Kita, Yoshikuni, Takashima, Naoyuki, Osawa, Haruhiko, Lee, So-Hyun, Shin, Min-Ho, Shin, Dong Hoon, Choi, Bo Youl, Shi, Jiajun, Gao, Yu-Tang, Xiang, Yong-Bing, Zheng, Wei, Kato, Norihiro, Yoon, Miwuk, He, Jiang, Shu, Xiao Ou, Ma, Ronald C.W., Kadowaki, Takashi, Jia, Weiping, Miki, Tetsuro, Qi, Lu, Tai, E Shyong, Mohlke, Karen L., Han, Bok-Ghee, Cho, Yoon Shin, and Kim, Bong-Jo

Published
2015
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44. Polyunsaturated fatty acids modulate the effect of TCF7L2 gene variants on postprandial lipemia

Author

Warodomwichit, Daruneewan, Arnett, Donna K., Kabagambe, Edmond K., Tsai, Michael Y., Hixson, James E., Straka, Robert J., Province, Michael, An, Ping, Lai, Chao-Qiang, Borecki, Ingrid, and Ordovas, Jose M.

Subjects
Unsaturated fatty acids -- Health aspects, Unsaturated fatty acids -- Genetic aspects, Lipemia -- Genetic aspects, DNA binding proteins -- Health aspects, Single nucleotide polymorphisms -- Health aspects, Metabolic syndrome X -- Genetic aspects, Genetic variation -- Research, Food/cooking/nutrition
Abstract

The transcription factor 7-like 2 (TCF7L2) has been recently associated with diabetes risk, and it may exert its effect through metabolic syndrome (MetS)-related traits and be subjected to modification by environmental factors. We investigated the effect of single nucleotide polymorphisms (SNP), rs7903146 and rs12255372, within the TCFTL2 locus on postprandial lipemia and other MetS-related traits and their modulation by dietary fat. Data were collected from 1083 European Americans participating in the Genetics of Lipid Lowering Drugs and Diet Network Study. Carriers of the minor T allele at the C/T rs7903146 SNP had higher fasting plasma glucose (P = 0.012), lower homeostasis model assessment of [beta] cell function (P = 0.041), higher plasma VLDL (P = 0.035), and lower large LDL particle (P = 0.007) concentrations and higher risk of MetS (P = 0.011) than CC individuals. Moreover, we identified significant interactions between this SNP and PUFA intake modulating fasting VLDL particle concentrations (P = 0.016) and postprandial triglycerides (TG) (P = 0.028), chylomicrons (P = 0.025), total VLDL (P = 0.026), and large VLDL (P = 0.018) concentrations. Thus, only T allele carriers with a PUFA intake [greater than or equal to] 7.36% of energy had elevated fasting plasma VLDL concentrations and postprandial TG-rich lipoproteins. These variables did not differ in T allele carriers and noncarriers in the low-PUFA intake group. Moreover, these significant interactions were due exclusively to (n-6) PUFA intake. In summary, high (n-6) PUFA intakes ([greater than or equal to] 6.62% of energy intake) were associated with atherogenic dyslipidemia in carriers of the minor T allele at the TCF7L2 rs7903146 SNP and may predispose them to MetS, diabetes, and cardiovascular disease.

Published
2009

46. Interleukin 1[beta] genetic polymorphisms interact with polyunsaturated fatty acids to modulate risk of the metabolic syndrome

Author

Shen, Jian, Arnett, Donna K., Peacock, James M., Parnell, Laurence D., Kraja, Aldi, Hixson, James E., Tsai, Michael Y., Lai, Chao-Qiang, Kabagambe, Edmond K., Straka, Robert J., and Ordovas, Jose M.

Subjects
Metabolic syndrome X -- Genetic aspects, Metabolic syndrome X -- Diet therapy, Metabolic syndrome X -- Physiological aspects, Metabolic syndrome X -- Chemical properties, Interleukin-1 -- Physiological aspects, Interleukin-1 -- Genetic aspects, Genetic polymorphisms -- Physiological aspects, Genetic polymorphisms -- Chemical properties, Unsaturated fatty acids -- Physiological aspects, Food/cooking/nutrition
Abstract

Chronic inflammation has been identified as an important component of the metabolic syndrome (MetS). Therefore, environmental and genetic factors contributing to the variation of inflammatory responses could affect individuals' susceptibility to MetS. We investigated the association between common IL 1[beta] genetic polymorphisms, inflammation, and the MetS, and the modulation of diet-related variables (i.e., erythrocyte membrane fatty acid composition) in a white U.S. population. IL 1[beta] single nucleotide polymorphisms (SNP) (-1473G > C, 511G > A, -31T > C, 3966C > T, 6054G > A), clinical and biochemical measurements were characterized in a total of 1120 subjects (540 males and 580 females) participating in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study. The 6054 G > A SNP was significantly associated with plasma C-reactive protein (P = 0.054), adiponectin (P=0.021), and the prevalence of MetS (P = 0.004). Moreover, there was a significant interaction between the 6054G > A SNP and erythrocyte membrane (n-3) PUFA (P = 0.019). Among subjects with low (n-3) PUFA content (below the median), the 6054 G allele was associated with increased risk of the MetS (OR = 3.29, 95%Cl = 1.49-7.26 for GG and OR = 1.95, 95%Cl = 0.854.46 for GA, P < 0.001) compared with the AA genotype, but there were no significant genotype associations among subjects with high (n-3) PUFA content (above the median). Further analyses supported a significant haplotype global effect on the MetS (P = 0.017) among subjects with low (n-3) PUFA content. These results suggested that IL 1[beta] genetic variants were associated with measures of chronic inflammation and the MetS risk, and that genetic influences were more evident among subjects with low (n-3) PUFA intake.

Published
2007

47. Novel and extendable genotyping system for human respiratory syncytial virus based on whole‐genome sequence analysis.

Author

Chen, Jiani, Qiu, Xueting, Avadhanula, Vasanthi, Shepard, Samuel S., Kim, Do‐Kyun, Hixson, James, Piedra, Pedro A., and Bahl, Justin

Subjects
RESPIRATORY syncytial virus, SEQUENCE analysis, RESPIRATORY organs, VACCINE development, RESPIRATORY infections, GENOTYPES
Abstract

Background: Human respiratory syncytial virus (RSV) is one of the leading causes of respiratory infections, especially in infants and young children. Previous RSV sequencing studies have primarily focused on partial sequencing of G gene (200–300 nucleotides) for genotype characterization or diagnostics. However, the genotype assignment with G gene has not recapitulated the phylogenetic signal of other genes, and there is no consensus on RSV genotype definition. Methods: We conducted maximum likelihood phylogenetic analysis with 10 RSV individual genes and whole‐genome sequence (WGS) that are published in GenBank. RSV genotypes were determined by using phylogenetic analysis and pair‐wise node distances. Results: In this study, we first statistically examined the phylogenetic incongruence, rate variation for each RSV gene sequence and WGS. We then proposed a new RSV genotyping system based on a comparative analysis of WGS and the temporal distribution of strains. We also provide an RSV classification tool to perform RSV genotype assignment and a publicly accessible up‐to‐date instance of Nextstrain where the phylogenetic relationship of all genotypes can be explored. Conclusions: This revised RSV genotyping system will provide important information for disease surveillance, epidemiology, and vaccine development. [ABSTRACT FROM AUTHOR]

Published
2022
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