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

Author

Katz, Daniel H, Tahir, Usman A, Bick, Alexander G, Pampana, Akhil, Ngo, Debby, Benson, Mark D, Yu, Zhi, Robbins, Jeremy M, Chen, Zsu-Zsu, Cruz, Daniel E, Deng, Shuliang, Farrell, Laurie, Sinha, Sumita, Schmaier, Alec A, Shen, Dongxiao, Gao, Yan, Hall, Michael E, Correa, Adolfo, Tracy, Russell P, Durda, Peter, Taylor, Kent D, Liu, Yongmei, Johnson, W Craig, Guo, Xiuqing, Yao, Jie, Ida Chen, Yii-Der, Manichaikul, Ani W, Jain, Deepti, Bouchard, Claude, Sarzynski, Mark A, Rich, Stephen S, Rotter, Jerome I, Wang, Thomas J, Wilson, James G, Natarajan, Pradeep, Gerszten, Robert E, 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, 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, Carty, Cara, Casaburi, Richard, Casas Romero, Juan P, Casella, James, Castaldi, Peter, Chaffin, Mark, Chang, Christy, Chang, Yi-Cheng, Chasman, Daniel, and Chavan, Sameer

Subjects
Epidemiology, Health Sciences, Aging, Heart Disease - Coronary Heart Disease, Human Genome, Genetics, Prevention, Cardiovascular, Heart Disease, Biotechnology, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Adult, Black People, Cardiovascular Diseases, Female, Genome-Wide Association Study, Humans, Male, Proteome, cardiovascular disease, genetics, proteomics, race and ethnicity, National Heart, Lung, and Blood Institute TOPMed (Trans-Omics for Precision Medicine) Consortium†, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Public Health and Health Services, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences, Sports science and exercise
Abstract

BackgroundPlasma proteins are critical mediators of cardiovascular processes and are the targets of many drugs. Previous efforts to characterize the genetic architecture of the plasma proteome have been limited by a focus on individuals of European descent and leveraged genotyping arrays and imputation. Here we describe whole genome sequence analysis of the plasma proteome in individuals with greater African ancestry, increasing our power to identify novel genetic determinants.MethodsProteomic profiling of 1301 proteins was performed in 1852 Black adults from the Jackson Heart Study using aptamer-based proteomics (SomaScan). Whole genome sequencing association analysis was ascertained for all variants with minor allele count ≥5. Results were validated using an alternative, antibody-based, proteomic platform (Olink) as well as replicated in the Multi-Ethnic Study of Atherosclerosis and the HERITAGE Family Study (Health, Risk Factors, Exercise Training and Genetics).ResultsWe identify 569 genetic associations between 479 proteins and 438 unique genetic regions at a Bonferroni-adjusted significance level of 3.8×10-11. These associations include 114 novel locus-protein relationships and an additional 217 novel sentinel variant-protein relationships. Novel cardiovascular findings include new protein associations at the APOE gene locus including ZAP70 (sentinel single nucleotide polymorphism [SNP] rs7412-T, β=0.61±0.05, P=3.27×10-30) and MMP-3 (β=-0.60±0.05, P=1.67×10-32), as well as a completely novel pleiotropic locus at the HPX gene, associated with 9 proteins. Further, the associations suggest new mechanisms of genetically mediated cardiovascular disease linked to African ancestry; we identify a novel association between variants linked to APOL1-associated chronic kidney and heart disease and the protein CKAP2 (rs73885319-G, β=0.34±0.04, P=1.34×10-17) as well as an association between ATTR amyloidosis and RBP4 levels in community-dwelling individuals without heart failure.ConclusionsTaken together, these results provide evidence for the functional importance of variants in non-European populations, and suggest new biological mechanisms for ancestry-specific determinants of lipids, coagulation, and myocardial function.

Published
2022

5. Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci.

Author

de Las Fuentes, Lisa, Sung, Yun Ju, Noordam, Raymond, Winkler, Thomas, Feitosa, Mary F, Schwander, Karen, Bentley, Amy R, Brown, Michael R, Guo, Xiuqing, Manning, Alisa, Chasman, Daniel I, Aschard, Hugues, Bartz, Traci M, Bielak, Lawrence F, Campbell, Archie, Cheng, Ching-Yu, Dorajoo, Rajkumar, Hartwig, Fernando P, Horimoto, ARVR, Li, Changwei, Li-Gao, Ruifang, Liu, Yongmei, Marten, Jonathan, Musani, Solomon K, Ntalla, Ioanna, Rankinen, Tuomo, Richard, Melissa, Sim, Xueling, Smith, Albert V, Tajuddin, Salman M, Tayo, Bamidele O, Vojinovic, Dina, Warren, Helen R, Xuan, Deng, Alver, Maris, Boissel, Mathilde, Chai, Jin-Fang, Chen, Xu, Christensen, Kaare, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Girotto, Giorgia, Harris, Sarah E, He, Meian, Hsu, Fang-Chi, Kühnel, Brigitte, Laguzzi, Federica, Li, Xiaoyin, Lyytikäinen, Leo-Pekka, Nolte, Ilja M, Poveda, Alaitz, Rauramaa, Rainer, Riaz, Muhammad, Rueedi, Rico, Shu, Xiao-Ou, Snieder, Harold, Sofer, Tamar, Takeuchi, Fumihiko, Verweij, Niek, Ware, Erin B, Weiss, Stefan, Yanek, Lisa R, Amin, Najaf, Arking, Dan E, Arnett, Donna K, Bergmann, Sven, Boerwinkle, Eric, Brody, Jennifer A, Broeckel, Ulrich, Brumat, Marco, Burke, Gregory, Cabrera, Claudia P, Canouil, Mickaël, Chee, Miao Li, Chen, Yii-Der Ida, Cocca, Massimiliano, Connell, John, de Silva, H Janaka, de Vries, Paul S, Eiriksdottir, Gudny, Faul, Jessica D, Fisher, Virginia, Forrester, Terrence, Fox, Ervin F, Friedlander, Yechiel, Gao, He, Gigante, Bruna, Giulianini, Franco, Gu, Chi Charles, Gu, Dongfeng, Harris, Tamara B, He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hunt, Steven, Ikram, M Arfan, Irvin, Marguerite R, Kähönen, Mika, and Kavousi, Maryam

Subjects
Lifelines Cohort Study, Psychiatry, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences
Abstract

Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, "Some College" (yes/no) and "Graduated College" (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P

Published
2021

6. Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry

Author

Graff, Mariaelisa, Justice, Anne E, Young, Kristin L, Marouli, Eirini, Zhang, Xinruo, Fine, Rebecca S, Lim, Elise, Buchanan, Victoria, Rand, Kristin, Feitosa, Mary F, Wojczynski, Mary K, Yanek, Lisa R, Shao, Yaming, Rohde, Rebecca, Adeyemo, Adebowale A, Aldrich, Melinda C, Allison, Matthew A, Ambrosone, Christine B, Ambs, Stefan, Amos, Christopher, Arnett, Donna K, Atwood, Larry, Bandera, Elisa V, Bartz, Traci, Becker, Diane M, Berndt, Sonja I, Bernstein, Leslie, Bielak, Lawrence F, Blot, William J, Bottinger, Erwin P, Bowden, Donald W, Bradfield, Jonathan P, Brody, Jennifer A, Broeckel, Ulrich, Burke, Gregory, Cade, Brian E, Cai, Qiuyin, Caporaso, Neil, Carlson, Chris, Carpten, John, Casey, Graham, Chanock, Stephen J, Chen, Guanjie, Chen, Minhui, Chen, Yii-Der I, Chen, Wei-Min, Chesi, Alessandra, Chiang, Charleston WK, Chu, Lisa, Coetzee, Gerry A, Conti, David V, Cooper, Richard S, Cushman, Mary, Demerath, Ellen, Deming, Sandra L, Dimitrov, Latchezar, Ding, Jingzhong, Diver, W Ryan, Duan, Qing, Evans, Michele K, Falusi, Adeyinka G, Faul, Jessica D, Fornage, Myriam, Fox, Caroline, Freedman, Barry I, Garcia, Melissa, Gillanders, Elizabeth M, Goodman, Phyllis, Gottesman, Omri, Grant, Struan FA, Guo, Xiuqing, Hakonarson, Hakon, Haritunians, Talin, Harris, Tamara B, Harris, Curtis C, Henderson, Brian E, Hennis, Anselm, Hernandez, Dena G, Hirschhorn, Joel N, McNeill, Lorna Haughton, Howard, Timothy D, Howard, Barbara, Hsing, Ann W, Hsu, Yu-Han H, Hu, Jennifer J, Huff, Chad D, Huo, Dezheng, Ingles, Sue A, Irvin, Marguerite R, John, Esther M, Johnson, Karen C, Jordan, Joanne M, Kabagambe, Edmond K, Kang, Sun J, Kardia, Sharon L, Keating, Brendan J, Kittles, Rick A, Klein, Eric A, Kolb, Suzanne, and Kolonel, Laurence N

Subjects
Human Genome, Genetics, Africa, Black or African American, Black People, Body Height, Europe, Female, Genome-Wide Association Study, Humans, Male, Polymorphism, Single Nucleotide, African ancestry, fine-mapping, genome-wide, height, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Although many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC). We additionally combined our African ancestry meta-analysis results with published European genome-wide association study (GWAS) data. In the African ancestry analyses, we identified three novel loci (SLC4A3, NCOA2, ECD/FAM149B1) in sex-combined results and two loci (CRB1, KLF6) in women only. In the African plus European sex-combined GWAS, we identified an additional three novel loci (RCCD1, G6PC3, CEP95) which were equally driven by AAAGC and European results. Among 39 genome-wide significant signals at known loci, conditioning index SNPs from European studies identified 20 secondary signals. Two of the 20 new secondary signals and none of the 8 novel loci had minor allele frequencies (MAF) < 5%. Of 802 known European height signals, 643 displayed directionally consistent associations with height, of which 205 were nominally significant (p < 0.05) in the African ancestry sex-combined sample. Furthermore, 148 of 241 loci contained ≤20 variants in the credible sets that jointly account for 99% of the posterior probability of driving the associations. In summary, trans-ethnic meta-analyses revealed novel signals and further improved fine-mapping of putative causal variants in loci shared between African and European ancestry populations.

Published
2021

7. 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. Multi-ancestry genome-wide association study accounting for gene-psychosocial factor interactions identifies novel loci for blood pressure traits

Author

Sun, Daokun, Richard, Melissa A, Musani, Solomon K, Sung, Yun Ju, Winkler, Thomas W, Schwander, Karen, Chai, Jin Fang, Guo, Xiuqing, Kilpeläinen, Tuomas O, Vojinovic, Dina, Aschard, Hugues, Bartz, Traci M, Bielak, Lawrence F, Brown, Michael R, Chitrala, Kumaraswamy, Hartwig, Fernando P, Horimoto, Andrea RVR, Liu, Yongmei, Manning, Alisa K, Noordam, Raymond, Smith, Albert V, Harris, Sarah E, Kühnel, Brigitte, Lyytikäinen, Leo-Pekka, Nolte, Ilja M, Rauramaa, Rainer, van der Most, Peter J, Wang, Rujia, Ware, Erin B, Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R, Arking, Dan E, Arnett, Donna K, Barac, Ana, Boerwinkle, Eric, Broeckel, Ulrich, Chakravarti, Aravinda, Chen, Yii-Der Ida, Cupples, L Adrienne, Davigulus, Martha L, de las Fuentes, Lisa, de Mutsert, Renée, de Vries, Paul S, Delaney, Joseph AC, Roux, Ana V Diez, Dörr, Marcus, Faul, Jessica D, Fretts, Amanda M, Gallo, Linda C, Grabe, Hans Jörgen, Gu, C Charles, Harris, Tamara B, Hartman, Catharina CA, Heikkinen, Sami, Ikram, M Arfan, Isasi, Carmen, Johnson, W Craig, Jonas, Jost Bruno, Kaplan, Robert C, Komulainen, Pirjo, Krieger, Jose E, Levy, Daniel, Study, Lifelines Cohort, Liu, Jianjun, Lohman, Kurt, Luik, Annemarie I, Martin, Lisa W, Meitinger, Thomas, Milaneschi, Yuri, O’Connell, Jeff R, Palmas, Walter R, Peters, Annette, Peyser, Patricia A, Pulkki-Råback, Laura, Raffel, Leslie J, Reiner, Alex P, Rice, Kenneth, Robinson, Jennifer G, Rosendaal, Frits R, Schmidt, Carsten Oliver, Schreiner, Pamela J, Schwettmann, Lars, Shikany, James M, Shu, Xiao-ou, Sidney, Stephen, Sims, Mario, Smith, Jennifer A, Sotoodehnia, Nona, Strauch, Konstantin, Tai, E Shyong, Taylor, Kent D, Uitterlinden, André G, van Duijn, Cornelia M, Waldenberger, Melanie, Wee, Hwee-Lin, Wei, Wen-Bin, Wilson, Gregory, Xuan, Deng, and Yao, Jie

Subjects
Hypertension, Mental Health, Genetics, Cardiovascular, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Lifelines Cohort Study
Abstract

Psychological and social factors are known to influence blood pressure (BP) and risk of hypertension and associated cardiovascular diseases. To identify novel BP loci, we carried out genome-wide association meta-analyses of systolic, diastolic, pulse, and mean arterial BP taking into account the interaction effects of genetic variants with three psychosocial factors: depressive symptoms, anxiety symptoms, and social support. Analyses were performed using a two-stage design in a sample of up to 128,894 adults from 5 ancestry groups. In the combined meta-analyses of Stages 1 and 2, we identified 59 loci (p value

Published
2021

10. Genomic integrity of human induced pluripotent stem cells across nine studies in the NHLBI NextGen program

Author

Kanchan, Kanika, Iyer, Kruthika, Yanek, Lisa R, Carcamo-Orive, Ivan, Taub, Margaret A, Malley, Claire, Baldwin, Kristin, Becker, Lewis C, Broeckel, Ulrich, Cheng, Linzhao, Cowan, Chad, D'Antonio, Matteo, Frazer, Kelly A, Quertermous, Thomas, Mostoslavsky, Gustavo, Murphy, George, Rabinovitch, Marlene, Rader, Daniel J, Steinberg, Martin H, Topol, Eric, Yang, Wenli, Knowles, Joshua W, Jaquish, Cashell E, Ruczinski, Ingo, and Mathias, Rasika A

Subjects
Biological Sciences, Genetics, Stem Cell Research - Induced Pluripotent Stem Cell - Human, Stem Cell Research - Induced Pluripotent Stem Cell, Biotechnology, Human Genome, Cancer, Stem Cell Research, 2.1 Biological and endogenous factors, Aetiology, Cell Differentiation, DNA Copy Number Variations, DNA-Binding Proteins, Genomic Instability, Genomics, Humans, Induced Pluripotent Stem Cells, National Heart, Lung, and Blood Institute (U.S.), United States, hiPSCs, Structural integrity, GWAS, VanillaICE, Oncogenes, Tumor suppressor genes, Medical and Health Sciences, Developmental Biology, Medical biotechnology, Oncology and carcinogenesis
Abstract

Human induced pluripotent stem cell (hiPSC) lines have previously been generated through the NHLBI sponsored NextGen program at nine individual study sites. Here, we examined the structural integrity of 506 hiPSC lines as determined by copy number variations (CNVs). We observed that 149 hiPSC lines acquired 258 CNVs relative to donor DNA. We identified six recurrent regions of CNVs on chromosomes 1, 2, 3, 16 and 20 that overlapped with cancer associated genes. Furthermore, the genes mapping to regions of acquired CNVs show an enrichment in cancer related biological processes (IL6 production) and signaling cascades (JNK cascade & NFκB cascade). The genomic region of instability on chr20 (chr20q11.2) includes transcriptomic signatures for cancer associated genes such as ID1, BCL2L1, TPX2, PDRG1 and HCK. Of these HCK shows statistically significant differential expression between carrier and non-carrier hiPSC lines. Overall, while a low level of genomic instability was observed in the NextGen generated hiPSC lines, the observation of structural instability in regions with known cancer associated genes substantiates the importance of systematic evaluation of genetic variations in hiPSCs before using them as disease/research models.

Published
2020

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

Author

Kachroo, Priyadarshini, Hecker, Julian, Chawes, Bo L, Ahluwalia, Tarunveer S, Cho, Michael H, Qiao, Dandi, Kelly, Rachel S, Chu, Su H, Virkud, Yamini V, Huang, Mengna, Barnes, Kathleen C, Burchard, Esteban G, Eng, Celeste, Hu, Donglei, Celedón, Juan C, Daya, Michelle, Levin, Albert M, Gui, Hongsheng, Williams, L Keoki, Forno, Erick, Mak, Angel CY, Avila, Lydiana, Soto-Quiros, Manuel E, Cloutier, Michelle M, Acosta-Pérez, Edna, Canino, Glorisa, Bønnelykke, Klaus, Bisgaard, Hans, Raby, Benjamin A, Lange, Christoph, Weiss, Scott T, Lasky-Su, Jessica A, National Heart, Lung, Abe, Namiko, Abecasis, Goncalo, Albert, Christine, Allred, Nicholette Palmer, 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, 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, and Das, Sayantan

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Clinical Research, Asthma, Genetics, Pediatric, Biotechnology, Human Genome, Lung, 2.1 Biological and endogenous factors, Respiratory, Adolescent, Adult, Cell Adhesion Molecules, Child, Child, Preschool, Costa Rica, Female, Forced Expiratory Volume, Humans, Interferon Regulatory Factors, Male, Middle Aged, Respiratory Physiological Phenomena, Vital Capacity, Whole Genome Sequencing, Young Adult, airway hyperresponsiveness, asthma, lung function, whole genome sequencing, National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine (TOPMed) Consortium, Respiratory System, Cardiovascular medicine and haematology, Clinical sciences
Abstract

BackgroundAsthma is a common respiratory disorder with a highly heterogeneous nature that remains poorly understood. The objective was to use whole genome sequencing (WGS) data to identify regions of common genetic variation contributing to lung function in individuals with a diagnosis of asthma.MethodsWGS data were generated for 1,053 individuals from trios and extended pedigrees participating in the family-based Genetic Epidemiology of Asthma in Costa Rica study. Asthma affection status was defined through a physician's diagnosis of asthma, and most participants with asthma also had airway hyperresponsiveness (AHR) to methacholine. Family-based association tests for single variants were performed to assess the associations with lung function phenotypes.ResultsA genome-wide significant association was identified between baseline FEV1/FVC ratio and a single-nucleotide polymorphism in the top hit cysteine-rich secretory protein LCCL domain-containing 2 (CRISPLD2) (rs12051168; P = 3.6 × 10-8 in the unadjusted model) that retained suggestive significance in the covariate-adjusted model (P = 5.6 × 10-6). Rs12051168 was also nominally associated with other related phenotypes: baseline FEV1 (P = 3.3 × 10-3), postbronchodilator (PB) FEV1 (7.3 × 10-3), and PB FEV1/FVC ratio (P = 2.7 × 10-3). The identified baseline FEV1/FVC ratio and rs12051168 association was meta-analyzed and replicated in three independent cohorts in which most participants with asthma also had confirmed AHR (combined weighted z-score P = .015) but not in cohorts without information about AHR.ConclusionsThese findings suggest that using specific asthma characteristics, such as AHR, can help identify more genetically homogeneous asthma subgroups with genotype-phenotype associations that may not be observed in all children with asthma. CRISPLD2 also may be important for baseline lung function in individuals with asthma who also may have AHR.

Published
2019

13. Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions

Author

de Vries, Paul S, Brown, Michael R, Bentley, Amy R, Sung, Yun J, Winkler, Thomas W, Ntalla, Ioanna, Schwander, Karen, Kraja, Aldi T, Guo, Xiuqing, Franceschini, Nora, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Huffman, Jennifer E, Musani, Solomon K, Li, Changwei, Feitosa, Mary F, Richard, Melissa A, Noordam, Raymond, Aschard, Hugues, Bartz, Traci M, Bielak, Lawrence F, Deng, Xuan, Dorajoo, Rajkumar, Lohman, Kurt K, Manning, Alisa K, Rankinen, Tuomo, Smith, Albert V, Tajuddin, Salman M, Evangelou, Evangelos, Graff, Mariaelisa, Alver, Maris, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gandin, Ilaria, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E, Hartwig, Fernando P, He, Meian, Horimoto, Andrea RVR, Hsu, Fang-Chi, Jackson, Anne U, Kasturiratne, Anuradhani, Komulainen, Pirjo, Kühnel, Brigitte, Laguzzi, Federica, Lee, Joseph H, Luan, Jian'an, Lyytikäinen, Leo-Pekka, Matoba, Nana, Nolte, Ilja M, Pietzner, Maik, Riaz, Muhammad, Said, M Abdullah, Scott, Robert A, Sofer, Tamar, Stančáková, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O, van der Most, Peter J, Varga, Tibor V, Wang, Yajuan, Ware, Erin B, Wen, Wanqing, Yanek, Lisa R, Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Amin, Najaf, Amini, Marzyeh, Arking, Dan E, Aung, Tin, Ballantyne, Christie, Boerwinkle, Eric, Broeckel, Ulrich, Campbell, Archie, Canouil, Mickaël, Charumathi, Sabanayagam, Chen, Yii-Der Ida, Connell, John M, de Faire, Ulf, de las Fuentes, Lisa, de Mutsert, Renée, de Silva, H Janaka, Ding, Jingzhong, Dominiczak, Anna F, Duan, Qing, Eaton, Charles B, Eppinga, Ruben N, Faul, Jessica D, Fisher, Virginia, Forrester, Terrence, Franco, Oscar H, Friedlander, Yechiel, Ghanbari, Mohsen, and Giulianini, Franco

Subjects
Epidemiology, Health Sciences, Substance Misuse, Alcoholism, Alcohol Use and Health, Human Genome, Prevention, Genetics, Aetiology, 2.1 Biological and endogenous factors, Cardiovascular, Adolescent, Adult, Aged, Alcohol Drinking, Cholesterol, HDL, Cholesterol, LDL, Female, Genome-Wide Association Study, Genotype, Humans, Life Style, Lipids, Male, Middle Aged, Phenotype, Racial Groups, Triglycerides, Vascular Endothelial Growth Factor B, Young Adult, alcohol consumption, cholesterol, gene-environment interactions, gene-lifestyle interactions, genome-wide association studies, lipids, triglycerides, InterAct Consortium, Lifelines Cohort, Groningen, The Netherlands, Mathematical Sciences, Medical and Health Sciences
Abstract

A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 × 10-6) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 × 10-8 using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.

Published
2019

14. Thymic regulatory T cells arise via two distinct developmental programs

Author

Owen, David L, Mahmud, Shawn A, Sjaastad, Louisa E, Williams, Jason B, Spanier, Justin A, Simeonov, Dimitre R, Ruscher, Roland, Huang, Weishan, Proekt, Irina, Miller, Corey N, Hekim, Can, Jeschke, Jonathan C, Aggarwal, Praful, Broeckel, Ulrich, LaRue, Rebecca S, Henzler, Christine M, Alegre, Maria-Luisa, Anderson, Mark S, August, Avery, Marson, Alexander, Zheng, Ye, Williams, Calvin B, and Farrar, Michael A

Subjects
Biomedical and Clinical Sciences, Immunology, HIV/AIDS, Stem Cell Research, Prevention, Aetiology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Animals, Autoantigens, Cell Differentiation, Colitis, Disease Models, Animal, Encephalomyelitis, Autoimmune, Experimental, Forkhead Transcription Factors, Freund's Adjuvant, Humans, Immune Tolerance, Interleukin-2 Receptor alpha Subunit, Lymphoid Progenitor Cells, Mice, Mice, Transgenic, Mycobacterium tuberculosis, Myelin-Oligodendrocyte Glycoprotein, Peptide Fragments, Signal Transduction, Specific Pathogen-Free Organisms, T-Lymphocytes, Regulatory, Thymus Gland, Biochemistry and cell biology
Abstract

The developmental programs that generate a broad repertoire of regulatory T cells (Treg cells) able to respond to both self antigens and non-self antigens remain unclear. Here we found that mature Treg cells were generated through two distinct developmental programs involving CD25+ Treg cell progenitors (CD25+ TregP cells) and Foxp3lo Treg cell progenitors (Foxp3lo TregP cells). CD25+ TregP cells showed higher rates of apoptosis and interacted with thymic self antigens with higher affinity than did Foxp3lo TregP cells, and had a T cell antigen receptor repertoire and transcriptome distinct from that of Foxp3lo TregP cells. The development of both CD25+ TregP cells and Foxp3lo TregP cells was controlled by distinct signaling pathways and enhancers. Transcriptomics and histocytometric data suggested that CD25+ TregP cells and Foxp3lo TregP cells arose by coopting negative-selection programs and positive-selection programs, respectively. Treg cells derived from CD25+ TregP cells, but not those derived from Foxp3lo TregP cells, prevented experimental autoimmune encephalitis. Our findings indicate that Treg cells arise through two distinct developmental programs that are both required for a comprehensive Treg cell repertoire capable of establishing immunotolerance.

Published
2019

15. Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries.

Author

Feitosa, Mary F, Kraja, Aldi T, Chasman, Daniel I, Sung, Yun J, Winkler, Thomas W, Ntalla, Ioanna, Guo, Xiuqing, Franceschini, Nora, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K, Li, Changwei, Bentley, Amy R, Brown, Michael R, Schwander, Karen, Richard, Melissa A, Noordam, Raymond, Aschard, Hugues, Bartz, Traci M, Bielak, Lawrence F, Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P, Horimoto, Andrea RVR, Lohman, Kurt K, Manning, Alisa K, Rankinen, Tuomo, Smith, Albert V, Tajuddin, Salman M, Wojczynski, Mary K, Alver, Maris, Boissel, Mathilde, Cai, Qiuyin, Campbell, Archie, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E, He, Meian, Hsu, Fang-Chi, Jackson, Anne U, Kähönen, Mika, Kasturiratne, Anuradhani, Komulainen, Pirjo, Kühnel, Brigitte, Laguzzi, Federica, Luan, Jian'an, Matoba, Nana, Nolte, Ilja M, Padmanabhan, Sandosh, Riaz, Muhammad, Rueedi, Rico, Robino, Antonietta, Said, M Abdullah, Scott, Robert A, Sofer, Tamar, Stančáková, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O, van der Most, Peter J, Varga, Tibor V, Vitart, Veronique, Wang, Yajuan, Ware, Erin B, Warren, Helen R, Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R, Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Amin, Najaf, Amini, Marzyeh, Arking, Dan E, Aung, Tin, Boerwinkle, Eric, Borecki, Ingrid, Broeckel, Ulrich, Brown, Morris, Brumat, Marco, Burke, Gregory L, Canouil, Mickaël, Chakravarti, Aravinda, Charumathi, Sabanayagam, Ida Chen, Yii-Der, Connell, John M, Correa, Adolfo, de Las Fuentes, Lisa, de Mutsert, Renée, de Silva, H Janaka, Deng, Xuan, Ding, Jingzhong, Duan, Qing, Eaton, Charles B, and Ehret, Georg

Subjects
InterAct Consortium, Humans, Hypertension, Genetic Predisposition to Disease, Cohort Studies, Pedigree, Alcohol Drinking, Blood Pressure, Polymorphism, Single Nucleotide, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Continental Population Groups, Female, Male, Genome-Wide Association Study, Young Adult, Gene-Environment Interaction, General Science & Technology
Abstract

Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.

Published
2018

16. Predicting oncology Drug-Induced cardiotoxicity with Donor-Specific iPSC-CMs—a proof-of-Concept study with doxorubicin

Author

Pang, Li, primary, Cai, Chengzhong, additional, Aggarwal, Praful, additional, Wang, Dong, additional, Vijay, Vikrant, additional, Bagam, Prathyusha, additional, Blamer, Jacob, additional, Matter, Andrea, additional, Turner, Amy, additional, Ren, Lijun, additional, Papineau, Katy, additional, Srinivasasainagendra, Vinodh, additional, Tiwari, Hemant K, additional, Yang, Xi, additional, Schnackenberg, Laura, additional, Mattes, William, additional, and Broeckel, Ulrich, additional

Published
2024
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17. Biomimetic fractal topography enhances podocyte maturation in vitro

Author

Liu, Chuan, primary, Aggarwal, Praful, additional, Wagner, Karl T., additional, Landau, Shira S., additional, Cui, Teng, additional, Song, Xin, additional, Shamaei, Laleh, additional, Rafatian, Naimeh, additional, Zhao, Yimu, additional, Rodriguez-Ramirez, Sonia, additional, Morton, Keith, additional, Virlee, Elizabeth, additional, Li, Chen Yu, additional, Bannerman, Dawn, additional, Pascual-Gil, Simon, additional, Okhovatian, Sargol, additional, Radisic, Anastasia, additional, Clotet-Freixas, Sergi, additional, Veres, Teodor, additional, Sadrzadeh, Mohtada, additional, Filleter, Tobin, additional, Broeckel, Ulrich, additional, Konvalinka, Ana, additional, and Radisic, Milica, additional

Published
2024
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20. Large-scale genome-wide analysis identifies genetic variants associated with cardiac structure and function

Author

Wild, Philipp S, Felix, Janine F, Schillert, Arne, Teumer, Alexander, Chen, Ming-Huei, Leening, Maarten JG, Völker, Uwe, Großmann, Vera, Brody, Jennifer A, Irvin, Marguerite R, Shah, Sanjiv J, Pramana, Setia, Lieb, Wolfgang, Schmidt, Reinhold, Stanton, Alice V, Malzahn, Dörthe, Smith, Albert Vernon, Sundström, Johan, Minelli, Cosetta, Ruggiero, Daniela, Lyytikäinen, Leo-Pekka, Tiller, Daniel, Smith, J Gustav, Monnereau, Claire, Di Tullio, Marco R, Musani, Solomon K, Morrison, Alanna C, Pers, Tune H, Morley, Michael, Kleber, Marcus E, Aragam, Jayashri, Benjamin, Emelia J, Bis, Joshua C, Bisping, Egbert, Broeckel, Ulrich, Cheng, Susan, Deckers, Jaap W, Del Greco M, Fabiola, Edelmann, Frank, Fornage, Myriam, Franke, Lude, Friedrich, Nele, Harris, Tamara B, Hofer, Edith, Hofman, Albert, Huang, Jie, Hughes, Alun D, Kähönen, Mika, investigators, KNHI, Kruppa, Jochen, Lackner, Karl J, Lannfelt, Lars, Laskowski, Rafael, Launer, Lenore J, Leosdottir, Margrét, Lin, Honghuang, Lindgren, Cecilia M, Loley, Christina, MacRae, Calum A, Mascalzoni, Deborah, Mayet, Jamil, Medenwald, Daniel, Morris, Andrew P, Müller, Christian, Müller-Nurasyid, Martina, Nappo, Stefania, Nilsson, Peter M, Nuding, Sebastian, Nutile, Teresa, Peters, Annette, Pfeufer, Arne, Pietzner, Diana, Pramstaller, Peter P, Raitakari, Olli T, Rice, Kenneth M, Rivadeneira, Fernando, Rotter, Jerome I, Ruohonen, Saku T, Sacco, Ralph L, Samdarshi, Tandaw E, Schmidt, Helena, Sharp, Andrew SP, Shields, Denis C, Sorice, Rossella, Sotoodehnia, Nona, Stricker, Bruno H, Surendran, Praveen, Thom, Simon, Töglhofer, Anna M, Uitterlinden, André G, Wachter, Rolf, Völzke, Henry, Ziegler, Andreas, Münzel, Thomas, März, Winfried, Cappola, Thomas P, Hirschhorn, Joel N, Mitchell, Gary F, Smith, Nicholas L, and Fox, Ervin R

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Human Genome, Clinical Research, Prevention, Heart Disease, Cardiovascular, 2.1 Biological and endogenous factors, Aetiology, Female, Genetic Loci, Genome-Wide Association Study, Heart Diseases, Humans, Male, Myocardium, Polymorphism, Single Nucleotide, Quantitative Trait, Heritable, Medical and Health Sciences, Immunology, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundUnderstanding the genetic architecture of cardiac structure and function may help to prevent and treat heart disease. This investigation sought to identify common genetic variations associated with inter-individual variability in cardiac structure and function.MethodsA GWAS meta-analysis of echocardiographic traits was performed, including 46,533 individuals from 30 studies (EchoGen consortium). The analysis included 16 traits of left ventricular (LV) structure, and systolic and diastolic function.ResultsThe discovery analysis included 21 cohorts for structural and systolic function traits (n = 32,212) and 17 cohorts for diastolic function traits (n = 21,852). Replication was performed in 5 cohorts (n = 14,321) and 6 cohorts (n = 16,308), respectively. Besides 5 previously reported loci, the combined meta-analysis identified 10 additional genome-wide significant SNPs: rs12541595 near MTSS1 and rs10774625 in ATXN2 for LV end-diastolic internal dimension; rs806322 near KCNRG, rs4765663 in CACNA1C, rs6702619 near PALMD, rs7127129 in TMEM16A, rs11207426 near FGGY, rs17608766 in GOSR2, and rs17696696 in CFDP1 for aortic root diameter; and rs12440869 in IQCH for Doppler transmitral A-wave peak velocity. Findings were in part validated in other cohorts and in GWAS of related disease traits. The genetic loci showed associations with putative signaling pathways, and with gene expression in whole blood, monocytes, and myocardial tissue.ConclusionThe additional genetic loci identified in this large meta-analysis of cardiac structure and function provide insights into the underlying genetic architecture of cardiac structure and warrant follow-up in future functional studies.FundingFor detailed information per study, see Acknowledgments.

Published
2017

23. 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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24. Directional dominance on stature and cognition in diverse human populations

Author

Joshi, Peter K, Esko, Tonu, Mattsson, Hannele, Eklund, Niina, Gandin, Ilaria, Nutile, Teresa, Jackson, Anne U, Schurmann, Claudia, Smith, Albert V, Zhang, Weihua, Okada, Yukinori, Stančáková, Alena, Faul, Jessica D, Zhao, Wei, Bartz, Traci M, Concas, Maria Pina, Franceschini, Nora, Enroth, Stefan, Vitart, Veronique, Trompet, Stella, Guo, Xiuqing, Chasman, Daniel I, O'Connel, Jeffrey R, Corre, Tanguy, Nongmaithem, Suraj S, Chen, Yuning, Mangino, Massimo, Ruggiero, Daniela, Traglia, Michela, Farmaki, Aliki-Eleni, Kacprowski, Tim, Bjonnes, Andrew, van der Spek, Ashley, Wu, Ying, Giri, Anil K, Yanek, Lisa R, Wang, Lihua, Hofer, Edith, Rietveld, Cornelius A, McLeod, Olga, Cornelis, Marilyn C, Pattaro, Cristian, Verweij, Niek, Baumbach, Clemens, Abdellaoui, Abdel, Warren, Helen R, Vuckovic, Dragana, Mei, Hao, Bouchard, Claude, Perry, John RB, Cappellani, Stefania, Mirza, Saira S, Benton, Miles C, Broeckel, Ulrich, Medland, Sarah E, Lind, Penelope A, Malerba, Giovanni, Drong, Alexander, Yengo, Loic, Bielak, Lawrence F, Zhi, Degui, van der Most, Peter J, Shriner, Daniel, Mägi, Reedik, Hemani, Gibran, Karaderi, Tugce, Wang, Zhaoming, Liu, Tian, Demuth, Ilja, Zhao, Jing Hua, Meng, Weihua, Lataniotis, Lazaros, van der Laan, Sander W, Bradfield, Jonathan P, Wood, Andrew R, Bonnefond, Amelie, Ahluwalia, Tarunveer S, Hall, Leanne M, Salvi, Erika, Yazar, Seyhan, Carstensen, Lisbeth, de Haan, Hugoline G, Abney, Mark, Afzal, Uzma, Allison, Matthew A, Amin, Najaf, Asselbergs, Folkert W, Bakker, Stephan JL, Barr, R Graham, Baumeister, Sebastian E, Benjamin, Daniel J, Bergmann, Sven, Boerwinkle, Eric, Bottinger, Erwin P, Campbell, Archie, Chakravarti, Aravinda, Chan, Yingleong, Chanock, Stephen J, Chen, Constance, and Chen, Y-D Ida

Subjects
Biological Sciences, Genetics, Clinical Research, Human Genome, Biological Evolution, Blood Pressure, Body Height, Cholesterol, LDL, Cognition, Cohort Studies, Educational Status, Female, Forced Expiratory Volume, Genome, Human, Homozygote, Humans, Lung Volume Measurements, Male, Phenotype, General Science & Technology
Abstract

Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.

Published
2015

27. Gene-educational attainment interactions in a multi-population genome-wide meta-analysis identify novel lipid loci

Author

de las Fuentes, Lisa, primary, Schwander, Karen L., additional, Brown, Michael R., additional, Bentley, Amy R., additional, Winkler, Thomas W., additional, Sung, Yun Ju, additional, Munroe, Patricia B., additional, Miller, Clint L., additional, Aschard, Hugo, additional, Aslibekyan, Stella, additional, Bartz, Traci M., additional, Bielak, Lawrence F., additional, Chai, Jin Fang, additional, Cheng, Ching-Yu, additional, Dorajoo, Rajkumar, additional, Feitosa, Mary F., additional, Guo, Xiuqing, additional, Hartwig, Fernando P., additional, Horimoto, Andrea, additional, Kolčić, Ivana, additional, Lim, Elise, additional, Liu, Yongmei, additional, Manning, Alisa K., additional, Marten, Jonathan, additional, Musani, Solomon K., additional, Noordam, Raymond, additional, Padmanabhan, Sandosh, additional, Rankinen, Tuomo, additional, Richard, Melissa A., additional, Ridker, Paul M., additional, Smith, Albert V., additional, Vojinovic, Dina, additional, Zonderman, Alan B., additional, Alver, Maris, additional, Boissel, Mathilde, additional, Christensen, Kaare, additional, Freedman, Barry I., additional, Gao, Chuan, additional, Giulianini, Franco, additional, Harris, Sarah E., additional, He, Meian, additional, Hsu, Fang-Chi, additional, Kühnel, Brigitte, additional, Laguzzi, Federica, additional, Li, Xiaoyin, additional, Lyytikäinen, Leo-Pekka, additional, Nolte, Ilja M., additional, Poveda, Alaitz, additional, Rauramaa, Rainer, additional, Riaz, Muhammad, additional, Robino, Antonietta, additional, Sofer, Tamar, additional, Takeuchi, Fumihiko, additional, Tayo, Bamidele O., additional, van der Most, Peter J., additional, Verweij, Niek, additional, Ware, Erin B., additional, Weiss, Stefan, additional, Wen, Wanqing, additional, Yanek, Lisa R., additional, Zhan, Yiqiang, additional, Amin, Najaf, additional, Arking, Dan E., additional, Ballantyne, Christie, additional, Boerwinkle, Eric, additional, Brody, Jennifer A., additional, Broeckel, Ulrich, additional, Campbell, Archie, additional, Canouil, Mickaël, additional, Chai, Xiaoran, additional, Chen, Yii-Der Ida, additional, Chen, Xu, additional, Chitrala, Kumaraswamy Naidu, additional, Concas, Maria Pina, additional, de Faire, Ulf, additional, de Mutsert, Renée, additional, de Silva, H. Janaka, additional, de Vries, Paul S., additional, Do, Ahn, additional, Faul, Jessica D., additional, Fisher, Virginia, additional, Floyd, James S., additional, Forrester, Terrence, additional, Friedlander, Yechiel, additional, Girotto, Giorgia, additional, Gu, C. Charles, additional, Hallmans, Göran, additional, Heikkinen, Sami, additional, Heng, Chew-Kiat, additional, Homuth, Georg, additional, Hunt, Steven, additional, Ikram, M. Arfan, additional, Jacobs, David R., additional, Kavousi, Maryam, additional, Khor, Chiea Chuen, additional, Kilpeläinen, Tuomas O., additional, Koh, Woon-Puay, additional, Komulainen, Pirjo, additional, Langefeld, Carl D., additional, Liang, Jingjing, additional, Liu, Kiang, additional, Liu, Jianjun, additional, Lohman, Kurt, additional, Mägi, Reedik, additional, Manichaikul, Ani W., additional, McKenzie, Colin A., additional, Meitinger, Thomas, additional, Milaneschi, Yuri, additional, Nauck, Matthias, additional, Nelson, Christopher P., additional, O’Connell, Jeffrey R., additional, Palmer, Nicholette D., additional, Pereira, Alexandre C., additional, Perls, Thomas, additional, Peters, Annette, additional, Polašek, Ozren, additional, Raitakari, Olli T., additional, Rice, Kenneth, additional, Rice, Treva K., additional, Rich, Stephen S., additional, Sabanayagam, Charumathi, additional, Schreiner, Pamela J., additional, Shu, Xiao-Ou, additional, Sidney, Stephen, additional, Sims, Mario, additional, Smith, Jennifer A., additional, Starr, John M., additional, Strauch, Konstantin, additional, Tai, E. Shyong, additional, Taylor, Kent D., additional, Tsai, Michael Y., additional, Uitterlinden, André G., additional, van Heemst, Diana, additional, Waldenberger, Melanie, additional, Wang, Ya-Xing, additional, Wei, Wen-Bin, additional, Wilson, Gregory, additional, Xuan, Deng, additional, Yao, Jie, additional, Yu, Caizheng, additional, Yuan, Jian-Min, additional, Zhao, Wei, additional, Becker, Diane M., additional, Bonnefond, Amélie, additional, Bowden, Donald W., additional, Cooper, Richard S., additional, Deary, Ian J., additional, Divers, Jasmin, additional, Esko, Tõnu, additional, Franks, Paul W., additional, Froguel, Philippe, additional, Gieger, Christian, additional, Jonas, Jost B., additional, Kato, Norihiro, additional, Lakka, Timo A., additional, Leander, Karin, additional, Lehtimäki, Terho, additional, Magnusson, Patrik K. E., additional, North, Kari E., additional, Ntalla, Ioanna, additional, Penninx, Brenda, additional, Samani, Nilesh J., additional, Snieder, Harold, additional, Spedicati, Beatrice, additional, van der Harst, Pim, additional, Völzke, Henry, additional, Wagenknecht, Lynne E., additional, Weir, David R., additional, Wojczynski, Mary K., additional, Wu, Tangchun, additional, Zheng, Wei, additional, Zhu, Xiaofeng, additional, Bouchard, Claude, additional, Chasman, Daniel I., additional, Evans, Michele K., additional, Fox, Ervin R., additional, Gudnason, Vilmundur, additional, Hayward, Caroline, additional, Horta, Bernardo L., additional, Kardia, Sharon L. R., additional, Krieger, Jose Eduardo, additional, Mook-Kanamori, Dennis O., additional, Peyser, Patricia A., additional, Province, Michael M., additional, Psaty, Bruce M., additional, Rudan, Igor, additional, Sim, Xueling, additional, Smith, Blair H., additional, van Dam, Rob M., additional, van Duijn, Cornelia M., additional, Wong, Tien Yin, additional, Arnett, Donna K., additional, Rao, Dabeeru C., additional, Gauderman, James, additional, Liu, Ching-Ti, additional, Morrison, Alanna C., additional, Rotter, Jerome I., additional, and Fornage, Myriam, additional

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

Author

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

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

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

Published
2013

31. A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry

Author

Monda, Keri L, Chen, Gary K, Taylor, Kira C, Palmer, Cameron, Edwards, Todd L, Lange, Leslie A, Ng, Maggie CY, Adeyemo, Adebowale A, Allison, Matthew A, Bielak, Lawrence F, Chen, Guanjie, Graff, Mariaelisa, Irvin, Marguerite R, Rhie, Suhn K, Li, Guo, Liu, Yongmei, Liu, Youfang, Lu, Yingchang, Nalls, Michael A, Sun, Yan V, Wojczynski, Mary K, Yanek, Lisa R, Aldrich, Melinda C, Ademola, Adeyinka, Amos, Christopher I, Bandera, Elisa V, Bock, Cathryn H, Britton, Angela, Broeckel, Ulrich, Cai, Quiyin, Caporaso, Neil E, Carlson, Chris S, Carpten, John, Casey, Graham, Chen, Wei-Min, Chen, Fang, Chen, Yii-Der I, Chiang, Charleston WK, Coetzee, Gerhard A, Demerath, Ellen, Deming-Halverson, Sandra L, Driver, Ryan W, Dubbert, Patricia, Feitosa, Mary F, Feng, Ye, Freedman, Barry I, Gillanders, Elizabeth M, Gottesman, Omri, Guo, Xiuqing, Haritunians, Talin, Harris, Tamara, Harris, Curtis C, Hennis, Anselm JM, Hernandez, Dena G, McNeill, Lorna H, Howard, Timothy D, Howard, Barbara V, Howard, Virginia J, Johnson, Karen C, Kang, Sun J, Keating, Brendan J, Kolb, Suzanne, Kuller, Lewis H, Kutlar, Abdullah, Langefeld, Carl D, Lettre, Guillaume, Lohman, Kurt, Lotay, Vaneet, Lyon, Helen, Manson, JoAnn E, Maixner, William, Meng, Yan A, Monroe, Kristine R, Morhason-Bello, Imran, Murphy, Adam B, Mychaleckyj, Josyf C, Nadukuru, Rajiv, Nathanson, Katherine L, Nayak, Uma, N'Diaye, Amidou, Nemesure, Barbara, Wu, Suh-Yuh, Leske, M Cristina, Neslund-Dudas, Christine, Neuhouser, Marian, Nyante, Sarah, Ochs-Balcom, Heather, Ogunniyi, Adesola, Ogundiran, Temidayo O, Ojengbede, Oladosu, Olopade, Olufunmilayo I, Palmer, Julie R, Ruiz-Narvaez, Edward A, Palmer, Nicholette D, Press, Michael F, Rampersaud, Evandine, Rasmussen-Torvik, Laura J, Rodriguez-Gil, Jorge L, Salako, Babatunde, and Schadt, Eric E

Subjects
Biological Sciences, Genetics, Human Genome, Black or African American, Body Mass Index, Case-Control Studies, Gene Frequency, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Obesity, Polymorphism, Single Nucleotide, NABEC Consortium, UKBEC Consortium, BioBank Japan Project, AGEN Consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Genome-wide association studies (GWAS) have identified 36 loci associated with body mass index (BMI), predominantly in populations of European ancestry. We conducted a meta-analysis to examine the association of >3.2 million SNPs with BMI in 39,144 men and women of African ancestry and followed up the most significant associations in an additional 32,268 individuals of African ancestry. We identified one new locus at 5q33 (GALNT10, rs7708584, P = 3.4 × 10(-11)) and another at 7p15 when we included data from the GIANT consortium (MIR148A-NFE2L3, rs10261878, P = 1.2 × 10(-10)). We also found suggestive evidence of an association at a third locus at 6q16 in the African-ancestry sample (KLHL32, rs974417, P = 6.9 × 10(-8)). Thirty-two of the 36 previously established BMI variants showed directionally consistent effect estimates in our GWAS (binomial P = 9.7 × 10(-7)), five of which reached genome-wide significance. These findings provide strong support for shared BMI loci across populations, as well as for the utility of studying ancestrally diverse populations.

Published
2013

32. Genome-wide association of body fat distribution in African ancestry populations suggests new loci.

Author

Liu, Ching-Ti, Monda, Keri L, Taylor, Kira C, Lange, Leslie, Demerath, Ellen W, Palmas, Walter, Wojczynski, Mary K, Ellis, Jaclyn C, Vitolins, Mara Z, Liu, Simin, Papanicolaou, George J, Irvin, Marguerite R, Xue, Luting, Griffin, Paula J, Nalls, Michael A, Adeyemo, Adebowale, Liu, Jiankang, Li, Guo, Ruiz-Narvaez, Edward A, Chen, Wei-Min, Chen, Fang, Henderson, Brian E, Millikan, Robert C, Ambrosone, Christine B, Strom, Sara S, Guo, Xiuqing, Andrews, Jeanette S, Sun, Yan V, Mosley, Thomas H, Yanek, Lisa R, Shriner, Daniel, Haritunians, Talin, Rotter, Jerome I, Speliotes, Elizabeth K, Smith, Megan, Rosenberg, Lynn, Mychaleckyj, Josyf, Nayak, Uma, Spruill, Ida, Garvey, W Timothy, Pettaway, Curtis, Nyante, Sarah, Bandera, Elisa V, Britton, Angela F, Zonderman, Alan B, Rasmussen-Torvik, Laura J, Chen, Yii-Der Ida, Ding, Jingzhong, Lohman, Kurt, Kritchevsky, Stephen B, Zhao, Wei, Peyser, Patricia A, Kardia, Sharon LR, Kabagambe, Edmond, Broeckel, Ulrich, Chen, Guanjie, Zhou, Jie, Wassertheil-Smoller, Sylvia, Neuhouser, Marian L, Rampersaud, Evadnie, Psaty, Bruce, Kooperberg, Charles, Manson, Joann E, Kuller, Lewis H, Ochs-Balcom, Heather M, Johnson, Karen C, Sucheston, Lara, Ordovas, Jose M, Palmer, Julie R, Haiman, Christopher A, McKnight, Barbara, Howard, Barbara V, Becker, Diane M, Bielak, Lawrence F, Liu, Yongmei, Allison, Matthew A, Grant, Struan FA, Burke, Gregory L, Patel, Sanjay R, Schreiner, Pamela J, Borecki, Ingrid B, Evans, Michele K, Taylor, Herman, Sale, Michele M, Howard, Virginia, Carlson, Christopher S, Rotimi, Charles N, Cushman, Mary, Harris, Tamara B, Reiner, Alexander P, Cupples, L Adrienne, North, Kari E, and Fox, Caroline S

Subjects
Humans, Obesity, Waist-Hip Ratio, Polymorphism, Single Nucleotide, African Continental Ancestry Group, European Continental Ancestry Group, Female, Male, Adiposity, Body Fat Distribution, Genome-Wide Association Study, Genetic Loci, Polymorphism, Single Nucleotide, Developmental Biology, Genetics
Abstract

Central obesity, measured by waist circumference (WC) or waist-hip ratio (WHR), is a marker of body fat distribution. Although obesity disproportionately affects minority populations, few studies have conducted genome-wide association study (GWAS) of fat distribution among those of predominantly African ancestry (AA). We performed GWAS of WC and WHR, adjusted and unadjusted for BMI, in up to 33,591 and 27,350 AA individuals, respectively. We identified loci associated with fat distribution in AA individuals using meta-analyses of GWA results for WC and WHR (stage 1). Overall, 25 SNPs with single genomic control (GC)-corrected p-values

Published
2013

35. Genome-wide meta-analysis points to CTC1 and ZNF676 as genes regulating telomere homeostasis in humans.

Author

Mangino, Massimo, Hwang, Shih-Jen, Spector, Timothy, Hunt, Steven, Kimura, Masayuki, Fitzpatrick, Annette, Christiansen, Lene, Petersen, Inge, Elbers, Clara, Harris, Tamara, Chen, Wei, Srinivasan, Sathanur, Kark, Jeremy, Benetos, Athanase, El Shamieh, Said, Visvikis-Siest, Sophie, Christensen, Kaare, Berenson, Gerald, Valdes, Ana, Viñuela, Ana, Garcia, Melissa, Arnett, Donna, Broeckel, Ulrich, Province, Michael, Pankow, James, Kammerer, Candace, Liu, Yongmei, Nalls, Michael, Tishkoff, Sarah, Thomas, Fridtjof, Psaty, Bruce, Bis, Joshua, Taylor, Kent, Smith, Erin, Schork, Nicholas, Levy, Daniel, Aviv, Abraham, Ziv, Elad, and Rotter, Jerome

Subjects
Genome-Wide Association Study, Humans, Kruppel-Like Transcription Factors, Telomere, Telomere Homeostasis, Telomere-Binding Proteins
Abstract

Leukocyte telomere length (LTL) is associated with a number of common age-related diseases and is a heritable trait. Previous genome-wide association studies (GWASs) identified two loci on chromosomes 3q26.2 (TERC) and 10q24.33 (OBFC1) that are associated with the inter-individual LTL variation. We performed a meta-analysis of 9190 individuals from six independent GWAS and validated our findings in 2226 individuals from four additional studies. We confirmed previously reported associations with OBFC1 (rs9419958 P = 9.1 × 10(-11)) and with the telomerase RNA component TERC (rs1317082, P = 1.1 × 10(-8)). We also identified two novel genomic regions associated with LTL variation that map near a conserved telomere maintenance complex component 1 (CTC1; rs3027234, P = 3.6 × 10(-8)) on chromosome17p13.1 and zinc finger protein 676 (ZNF676; rs412658, P = 3.3 × 10(-8)) on 19p12. The minor allele of rs3027234 was associated with both shorter LTL and lower expression of CTC1. Our findings are consistent with the recent observations that point mutations in CTC1 cause short telomeres in both Arabidopsis and humans affected by a rare Mendelian syndrome. Overall, our results provide novel insights into the genetic architecture of inter-individual LTL variation in the general population.

Published
2012

38. Multisite Assessment of Optical Genome Mapping for Analysis of Structural Variants in Constitutional Postnatal Cases

Author

Iqbal, M. Anwar, primary, Broeckel, Ulrich, additional, Levy, Brynn, additional, Skinner, Steven, additional, Sahajpal, Nikhil S., additional, Rodriguez, Vanessa, additional, Stence, Aaron, additional, Awayda, Kamel, additional, Scharer, Gunter, additional, Skinner, Cindy, additional, Stevenson, Roger, additional, Bossler, Aaron, additional, Nagy, Peter L., additional, and Kolhe, Ravindra, additional

Published
2023
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39. Gene-educational attainment interactions in a multi-population genome-wide meta-analysis identify novel lipid loci

Author

de las Fuentes, Lisa, Schwander, Karen L., Brown, Michael R., Bentley, Amy R., Winkler, Thomas W., Sung, Yun Ju, Munroe, Patricia B., Miller, Clint L., Aschard, Hugo, Aslibekyan, Stella, Bartz, Traci M., Bielak, Lawrence F., Chai, Jin Fang, Cheng, Ching Yu, Dorajoo, Rajkumar, Feitosa, Mary F., Guo, Xiuqing, Hartwig, Fernando P., Horimoto, Andrea, Kolčić, Ivana, Lim, Elise, Liu, Yongmei, Manning, Alisa K., Marten, Jonathan, Musani, Solomon K., Noordam, Raymond, Padmanabhan, Sandosh, Rankinen, Tuomo, Richard, Melissa A., Ridker, Paul M., Smith, Albert V., Vojinovic, Dina, Zonderman, Alan B., Alver, Maris, Boissel, Mathilde, Christensen, Kaare, Freedman, Barry I., Gao, Chuan, Giulianini, Franco, Harris, Sarah E., He, Meian, Hsu, Fang Chi, Kühnel, Brigitte, Laguzzi, Federica, Li, Xiaoyin, Lyytikäinen, Leo Pekka, Nolte, Ilja M., Poveda, Alaitz, Rauramaa, Rainer, Riaz, Muhammad, Robino, Antonietta, Sofer, Tamar, Takeuchi, Fumihiko, Tayo, Bamidele O., van der Most, Peter J., Verweij, Niek, Ware, Erin B., Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R., Zhan, Yiqiang, Amin, Najaf, Arking, Dan E., Ballantyne, Christie, Boerwinkle, Eric, Brody, Jennifer A., Broeckel, Ulrich, Campbell, Archie, Canouil, Mickaël, Chai, Xiaoran, Chen, Yii Der Ida, Chen, Xu, Chitrala, Kumaraswamy Naidu, Concas, Maria Pina, de Faire, Ulf, de Mutsert, Renée, de Silva, H. Janaka, de Vries, Paul S., Do, Ahn, Faul, Jessica D., Fisher, Virginia, Floyd, James S., Forrester, Terrence, Friedlander, Yechiel, Girotto, Giorgia, Gu, C. Charles, Hallmans, Göran, Heikkinen, Sami, Heng, Chew Kiat, Homuth, Georg, Hunt, Steven, Ikram, M. Arfan, Jacobs, David R., Kavousi, Maryam, Khor, Chiea Chuen, Kilpeläinen, Tuomas O., Koh, Woon Puay, Komulainen, Pirjo, Langefeld, Carl D., Liang, Jingjing, Liu, Kiang, Liu, Jianjun, Lohman, Kurt, Mägi, Reedik, Manichaikul, Ani W., McKenzie, Colin A., Meitinger, Thomas, Milaneschi, Yuri, Nauck, Matthias, Nelson, Christopher P., O’Connell, Jeffrey R., Palmer, Nicholette D., Pereira, Alexandre C., Perls, Thomas, Peters, Annette, Polašek, Ozren, Raitakari, Olli T., Rice, Kenneth, Rice, Treva K., Rich, Stephen S., Sabanayagam, Charumathi, Schreiner, Pamela J., Shu, Xiao Ou, Sidney, Stephen, Sims, Mario, Smith, Jennifer A., Starr, John M., Strauch, Konstantin, Tai, E. Shyong, Taylor, Kent D., Tsai, Michael Y., Uitterlinden, André G., van Heemst, Diana, Waldenberger, Melanie, Wang, Ya Xing, Wei, Wen Bin, Wilson, Gregory, Xuan, Deng, Yao, Jie, Yu, Caizheng, Yuan, Jian Min, Zhao, Wei, Becker, Diane M., Bonnefond, Amélie, Bowden, Donald W., Cooper, Richard S., Deary, Ian J., Divers, Jasmin, Esko, Tõnu, Franks, Paul W., Froguel, Philippe, Gieger, Christian, Jonas, Jost B., Kato, Norihiro, Lakka, Timo A., Leander, Karin, Lehtimäki, Terho, Magnusson, Patrik K.E., North, Kari E., Ntalla, Ioanna, Penninx, Brenda, Samani, Nilesh J., Snieder, Harold, Spedicati, Beatrice, van der Harst, Pim, Völzke, Henry, Wagenknecht, Lynne E., Weir, David R., Wojczynski, Mary K., Wu, Tangchun, Zheng, Wei, Zhu, Xiaofeng, Bouchard, Claude, Chasman, Daniel I., Evans, Michele K., Fox, Ervin R., Gudnason, Vilmundur, Hayward, Caroline, Horta, Bernardo L., Kardia, Sharon L.R., Krieger, Jose Eduardo, Mook-Kanamori, Dennis O., Peyser, Patricia A., Province, Michael M., Psaty, Bruce M., Rudan, Igor, Sim, Xueling, Smith, Blair H., van Dam, Rob M., van Duijn, Cornelia M., Wong, Tien Yin, Arnett, Donna K., Rao, Dabeeru C., Gauderman, James, Liu, Ching Ti, Morrison, Alanna C., Rotter, Jerome I., Fornage, Myriam, de las Fuentes, Lisa, Schwander, Karen L., Brown, Michael R., Bentley, Amy R., Winkler, Thomas W., Sung, Yun Ju, Munroe, Patricia B., Miller, Clint L., Aschard, Hugo, Aslibekyan, Stella, Bartz, Traci M., Bielak, Lawrence F., Chai, Jin Fang, Cheng, Ching Yu, Dorajoo, Rajkumar, Feitosa, Mary F., Guo, Xiuqing, Hartwig, Fernando P., Horimoto, Andrea, Kolčić, Ivana, Lim, Elise, Liu, Yongmei, Manning, Alisa K., Marten, Jonathan, Musani, Solomon K., Noordam, Raymond, Padmanabhan, Sandosh, Rankinen, Tuomo, Richard, Melissa A., Ridker, Paul M., Smith, Albert V., Vojinovic, Dina, Zonderman, Alan B., Alver, Maris, Boissel, Mathilde, Christensen, Kaare, Freedman, Barry I., Gao, Chuan, Giulianini, Franco, Harris, Sarah E., He, Meian, Hsu, Fang Chi, Kühnel, Brigitte, Laguzzi, Federica, Li, Xiaoyin, Lyytikäinen, Leo Pekka, Nolte, Ilja M., Poveda, Alaitz, Rauramaa, Rainer, Riaz, Muhammad, Robino, Antonietta, Sofer, Tamar, Takeuchi, Fumihiko, Tayo, Bamidele O., van der Most, Peter J., Verweij, Niek, Ware, Erin B., Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R., Zhan, Yiqiang, Amin, Najaf, Arking, Dan E., Ballantyne, Christie, Boerwinkle, Eric, Brody, Jennifer A., Broeckel, Ulrich, Campbell, Archie, Canouil, Mickaël, Chai, Xiaoran, Chen, Yii Der Ida, Chen, Xu, Chitrala, Kumaraswamy Naidu, Concas, Maria Pina, de Faire, Ulf, de Mutsert, Renée, de Silva, H. Janaka, de Vries, Paul S., Do, Ahn, Faul, Jessica D., Fisher, Virginia, Floyd, James S., Forrester, Terrence, Friedlander, Yechiel, Girotto, Giorgia, Gu, C. Charles, Hallmans, Göran, Heikkinen, Sami, Heng, Chew Kiat, Homuth, Georg, Hunt, Steven, Ikram, M. Arfan, Jacobs, David R., Kavousi, Maryam, Khor, Chiea Chuen, Kilpeläinen, Tuomas O., Koh, Woon Puay, Komulainen, Pirjo, Langefeld, Carl D., Liang, Jingjing, Liu, Kiang, Liu, Jianjun, Lohman, Kurt, Mägi, Reedik, Manichaikul, Ani W., McKenzie, Colin A., Meitinger, Thomas, Milaneschi, Yuri, Nauck, Matthias, Nelson, Christopher P., O’Connell, Jeffrey R., Palmer, Nicholette D., Pereira, Alexandre C., Perls, Thomas, Peters, Annette, Polašek, Ozren, Raitakari, Olli T., Rice, Kenneth, Rice, Treva K., Rich, Stephen S., Sabanayagam, Charumathi, Schreiner, Pamela J., Shu, Xiao Ou, Sidney, Stephen, Sims, Mario, Smith, Jennifer A., Starr, John M., Strauch, Konstantin, Tai, E. Shyong, Taylor, Kent D., Tsai, Michael Y., Uitterlinden, André G., van Heemst, Diana, Waldenberger, Melanie, Wang, Ya Xing, Wei, Wen Bin, Wilson, Gregory, Xuan, Deng, Yao, Jie, Yu, Caizheng, Yuan, Jian Min, Zhao, Wei, Becker, Diane M., Bonnefond, Amélie, Bowden, Donald W., Cooper, Richard S., Deary, Ian J., Divers, Jasmin, Esko, Tõnu, Franks, Paul W., Froguel, Philippe, Gieger, Christian, Jonas, Jost B., Kato, Norihiro, Lakka, Timo A., Leander, Karin, Lehtimäki, Terho, Magnusson, Patrik K.E., North, Kari E., Ntalla, Ioanna, Penninx, Brenda, Samani, Nilesh J., Snieder, Harold, Spedicati, Beatrice, van der Harst, Pim, Völzke, Henry, Wagenknecht, Lynne E., Weir, David R., Wojczynski, Mary K., Wu, Tangchun, Zheng, Wei, Zhu, Xiaofeng, Bouchard, Claude, Chasman, Daniel I., Evans, Michele K., Fox, Ervin R., Gudnason, Vilmundur, Hayward, Caroline, Horta, Bernardo L., Kardia, Sharon L.R., Krieger, Jose Eduardo, Mook-Kanamori, Dennis O., Peyser, Patricia A., Province, Michael M., Psaty, Bruce M., Rudan, Igor, Sim, Xueling, Smith, Blair H., van Dam, Rob M., van Duijn, Cornelia M., Wong, Tien Yin, Arnett, Donna K., Rao, Dabeeru C., Gauderman, James, Liu, Ching Ti, Morrison, Alanna C., Rotter, Jerome I., and Fornage, Myriam

Abstract

Introduction: Educational attainment, widely used in epidemiologic studies as a surrogate for socioeconomic status, is a predictor of cardiovascular health outcomes. Methods:A two-stage genome-wide meta-analysis of low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TG) levels was performed while accounting for gene-educational attainment interactions in up to 226,315 individuals from five population groups. We considered two educational attainment variables: “Some College” (yes/no, for any education beyond high school) and “Graduated College” (yes/no, for completing a 4-year college degree). Genome-wide significant (p < 5 × 10−8) and suggestive (p < 1 × 10−6) variants were identified in Stage 1 (in up to 108,784 individuals) through genome-wide analysis, and those variants were followed up in Stage 2 studies (in up to 117,531 individuals). Results: In combined analysis of Stages 1 and 2, we identified 18 novel lipid loci (nine for LDL, seven for HDL, and two for TG) by two degree-of-freedom (2 DF) joint tests of main and interaction effects. Four loci showed significant interaction with educational attainment. Two loci were significant only in cross-population analyses. Several loci include genes with known or suggested roles in adipose (FOXP1, MBOAT4, SKP2, STIM1, STX4), brain (BRI3, FILIP1, FOXP1, LINC00290, LMTK2, MBOAT4, MYO6, SENP6, SRGAP3, STIM1, TMEM167A, TMEM30A), and liver (BRI3, FOXP1) biology, highlighting the potential importance of brain-adipose-liver communication in the regulation of lipid metabolism. An investigation of the potential druggability of genes in identified loci resulted in five gene targets shown to interact with drugs approved by the Food and Drug Administration, including genes with roles in adipose and brain tissue.Discussion: Genome-wide interaction analysis of educational a

Published
2023

43. Multisite Study of Optical Genome Mapping of Retrospective and Prospective Constitutional Disorder Cohorts

Author

Broeckel, Ulrich, primary, Iqbal, M. Anwar, additional, Levy, Brynn, additional, Sahajpal, Nikhil, additional, Nagy, Peter L., additional, Scharer, Gunter, additional, Bossler, Aaron D., additional, Rodriguez, Vanessa, additional, Stence, Aaron, additional, Skinner, Cindy, additional, Skinner, Steven A, additional, Kolhe, Ravindra, additional, and Stevenson, Roger, additional

Published
2022
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44. Characterization of Reference Materials for TPMT and NUDT15

Author

Pratt, Victoria M., primary, Wang, Wendy Y., additional, Boone, Erin C., additional, Broeckel, Ulrich, additional, Cody, Neal, additional, Edelmann, Lisa, additional, Gaedigk, Andrea, additional, Lynnes, Ty C., additional, Medeiros, Elizabeth B., additional, Moyer, Ann M., additional, Mitchell, Matthew W., additional, Scott, Stuart A., additional, Starostik, Petr, additional, Turner, Amy, additional, and Kalman, Lisa V., additional

Published
2022
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48. 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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50. 6. Optical genome mapping as a potential Tier1 test for Postnatal Chromosomal Disorders – results of multi-institutional validation study of 331 retrospective clinical samples

Author

Iqbal, M. Anwar, primary, Broeckel, Ulrich, additional, Levy, Brynn, additional, Skinner, Steven, additional, Sahajpal, Nikhil, additional, Rodriguez, Vanessa, additional, Stence, Aaron, additional, Awayda, Kamel, additional, Scharer, Gunter, additional, Skinner, Cindy, additional, Stevenson, Roger, additional, Bossler, Aaron, additional, Nagy, Peter L., additional, and Kolhe, Ravindra, additional

Published
2022
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