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

Author

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

Subjects
Adult, Male, Proteomics, Aging, Whole genome sequence analysis, Proteome, Clinical Sciences, Black People, Disease, Computational biology, race and ethnicity, Cardiorespiratory Medicine and Haematology, Cardiovascular, Article, proteomics, cardiovascular disease, Physiology (medical), Genetics, 2.1 Biological and endogenous factors, Humans, Medicine, Aetiology, Lung, Heart Disease - Coronary Heart Disease, and Blood Institute TOPMed (Trans-Omics for Precision Medicine) Consortium†, business.industry, Prevention, Human Genome, National Heart, Genomics, Blood proteins, Genetic architecture, Heart Disease, Good Health and Well Being, Cardiovascular System & Hematology, Cardiovascular Diseases, Public Health and Health Services, Female, Cardiology and Cardiovascular Medicine, business, Biotechnology, Genome-Wide Association Study
Abstract

Background: Plasma 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. Methods: Proteomic 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). Results: We 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. Conclusions: Taken 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

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

Author

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

Subjects
Adult, Costa Rica, Male, Pulmonary and Respiratory Medicine, Adolescent, Vital Capacity, Single-nucleotide polymorphism, Pedigree chart, Critical Care and Intensive Care Medicine, Young Adult, 03 medical and health sciences, FEV1/FVC ratio, 0302 clinical medicine, Polymorphism (computer science), Forced Expiratory Volume, Humans, Medicine, SNP, 030212 general & internal medicine, Child, Asthma, Whole Genome Sequencing, business.industry, Middle Aged, respiratory system, medicine.disease, respiratory tract diseases, Minor allele frequency, 030228 respiratory system, Genetic epidemiology, Child, Preschool, Interferon Regulatory Factors, Immunology, Respiratory Physiological Phenomena, Female, Cardiology and Cardiovascular Medicine, business, Cell Adhesion Molecules
Abstract

BACKGROUND: Asthma 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. METHODS: WGS 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. RESULTS: A genome-wide significant association was identified between baseline FEV(1)/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 FEV(1) (P = 3.3 × 10(−3)), postbronchodilator (PB) FEV(1) (7.3 × 10(−3)), and PB FEV(1)/FVC ratio (P = 2.7 × 10(−3)). The identified baseline FEV(1)/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. CONCLUSIONS: These 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

3. Abstract P530: Pleiotropic Effects on Blood Pressure Traits Using Genome-wide Analysis of Gene-alcohol Interactions

Author

Aldi T Kraja, Mary F Feitosa, Daniel Chasman, Yun J Sung, Thomas W Winkler, Ioanna Ntalla, Hugues Aschard, Kenneth Rice, Alisa K Manning, Jeffrey O’Connell, Sharon L Kardia, Patricia Munroe, L. Adrienne Cupples, Alana Morrison, W. James Gauderman, Daniel Levy, D.C. Rao, Xiaofeng Zhu, Michael A Province, on behalf of the CHARGE Gene-Lifestyle Interactions, and This work is supported in part by the NHLBI grant HL 118305

Subjects
Internal Medicine
Abstract

We tested for pleiotropy in European ancestry subjects (N>90K) via GWAS of systolic and diastolic blood pressure (BP), mean arterial pressure, and pulse pressure, using gene (G)-alcohol consumption (E) interactions. The approach was a correlated meta-analysis (PMCID-PMC3773990) that combined simultaneously the 4 BP traits genome-wide GxE interactions summary meta-P values. This approach adjusts for correlations among single traits at the genomic level. A variant was considered pleiotropic when the overall correlated meta-analysis yielded P ≤5E-08 and GxE meta- P ≤E-04 for at least two single traits. The novel pleiotropic variants localize in eight loci. TTLL7 (1p31.1) is a tubulin modifier. DYRK3 (1q32.1) is a transcription regulator. MAPKAPK2 (1q32.1) is a stress-activated serine/threonine-protein kinase involved in cytokine production especially for TNF , IL6 and phosphorylates (among others) LSP1 , identified in our GWAS GxE study for individual BP traits. FSTL5 (4q32.2) is annotated as calcium ion binding . A locus at 11q13.1 includes SNX32 , EFEMP2, and FOSL1 . FOSL1 variants may regulate expression of SNX32 . EFEMP2 is implicated in blood coagulation. CATSPER2 (15q15.3) is a cation channel. CCDC151 (19p13.2) is an outer dynein arm assembly. The functions of two other loci (17q22 and 18q22.3) are unknown. We also identified 4 pleiotropic loci ( SGK223 , TNKS , GATA4 , FTO ) that were found significant at our GxE meta-GWAS of single traits in 572K multi-ancestry individuals. In addition, we detected 24 pleiotropic BP-known loci. Some of these genes relate to alcohol consumption (e.g., BLK , GATA4 , FTO ). TNKS , MAPKAPK2 and FSTL5 interact with the Wnt/β-catenin signaling pathway, which contributes to hypertension. Several pleiotropic variants showed features of regulation by locating at promoter and enhancer histone marks, at DNAse, at proteins binding sites and being eQTL. The 36 novel and BP-known loci comprising 86 significant genes were enriched for Hypertension , Cardiac arrhythmias , Myocardial infarction , Atrial fibrillation, and Left ventricular hypertrophy . Our correlated meta-analysis of GxE interaction approach identified novel pleiotropic loci and validated known BP loci, thus providing insights into the mechanisms of hypertension.

Published
2017

4. Contents Vol. 29, 2009

Author

Ching-Ha Bonnie Kwan, Abdul Rashid Qureshi, Mehdi Rambod, Kam-Tao Philip Li, Manuel Carlos Martins Castro, Joel D. Kopple, Deborah Benner, Karl Tryggvason, Ying Sun, Robert H. Weiss, James S. Kaufman, Jasmin Divers, Hung-Chun Chen, Christiane Rüster, Chih-Ken Chen, Timothy P. Ryan, Paul Winters, Gunter Wolf, Robert T. Neff, Bengt Lindholm, Ajay K. Singh, Mai-Szu Wu, Jaakko Patrakka, D.C. Rao, Jeffrey B. Kopp, Peter Stenvinkel, Ka-Bik Lai, Rosilene M. Elias, Christina Thies, Qunying Guo, Hyun Ju Kim, João Egidio Romão-Junior, Pamela J. Hicks, Edward M. Falta, Jennifer Zitterkoph, Kamyar Kalantar-Zadeh, Frank P. Hurst, Hugo Abensur, Fernand Mac-Moune Lai, James Tacci, Steven C. Hunt, Gang Wang, M. Cignarelli, S. Fariello, Chih-Hung Lee, Masahide Mizobuchi, Sai Ram Keithi-Reddy, Jonas Axelsson, Liqun He, Hiroshi Yamamoto, Zohra Tumur, Timo Pikkarainen, Eric A. Elster, Nobushige Tanaka, Xiaoyan Zhou, Edward D. Frohlich, Juhi Pithia, Barry I. Freedman, Carl D. Langefeld, Sunna Snaedal, Heng Jung Hsu, Mark Leppert, Kevin C. Abbott, Mohamed Cheikhalfraj, Masanori Tokumoto, Eduardo Lyra de Queiroz, Geraldo Lorenzi-Filho, Jin Young Park, Wolfgang Pommer, Toshimitsu Niwa, Rahul M. Jindal, L. Gesualdo, G. Stallone, Sybille Franke, Kai-Ming Chow, George W. Nelson, Susan G. Fisher, Rachelle Bross, Christer Betsholtz, O. Lamacchia, Jessica L. Elder, Dinko Susic, Katarina Truvé, Nosratola D. Vaziri, Chi-Chih Hung, Jane Finch, Jenny Norlin, Antje Wittstock, Tzvetanka Bondeva, Domenic J. Reda, Wan-Chun Liu, D. Camarchio, Alexandra Scholze, Csaba P. Kovesdy, Daniel R. Martin, See-Hyoung Park, Mei-Chuan Kuo, Tejas V. Patel, Neal P. Das, Guillem Genové, Angie Hirter, Cheuk-Chun Szeto, S. Pinnelli, Martin Tepel, Minoru Takemoto, Shang-Jyh Hwang, Hironori Nakamura, James A. Sloand, William S. Beckett, John H. Eckfeldt, Olof Heimbürger, Peter Bárány, Walter Zidek, Cheryl A. Winkler, and Eduardo Slatopolsky

Subjects
Traditional medicine, Nephrology, business.industry, Medicine, business
Published
2009

5. Associations between angiotensinogen gene variants and left ventricular mass and function in the HyperGEN study

Author

Paul N. Hopkins, Albert Oberman, D.C. Rao, Dalane W. Kitzman, Donna K. Arnett, Richard B. Devereux, and Weihong Tang

Subjects
Male, medicine.medical_specialty, Population level, Angiotensinogen, Genetic determinism, Left ventricular mass, Ventricular Dysfunction, Left, Polymorphism (computer science), Internal medicine, medicine, Humans, In patient, Body surface area, Analysis of Variance, Polymorphism, Genetic, business.industry, Middle Aged, Cross-Sectional Studies, Endocrinology, Blood pressure, Hypertension, Angiotensinogen gene, Female, Hypertrophy, Left Ventricular, Cardiology and Cardiovascular Medicine, business
Abstract

The angiotensinogen M235T polymorphism is positively associated with plasma angiotensinogen, hypertension, and coronary heart disease. However, the association of M235T polymorphism with left ventricular (LV) mass and function is not well defined at the population level. We investigated whether 2 tightly linked polymorphisms of angiotensinogen gene, M235T and G-6A, are associated with LV mass and function in a large population-based sample, composed mostly of patients with hypertension.Two-dimensional guided M-mode and pulsed Doppler scan echocardiograms were performed in 605 participants. The angiotensinogen M235T was analyzed with a standard polymerase chain reaction test, and the G-6A variant was measured with mass spectrophotometry.The association of angiotensinogen gene to LV mass and LV mass indexed to body surface area (LVMI) differed significantly between subjects with normotensive and hypertensive conditions with respect to the direction of association (P.005). The methionine-threonine/threonine-threonine genotype was negatively associated with LV mass and LVMI in patients with hypertension after adjustment for blood pressure, antihypertensive medication use, weight, and other covariates (P.001), and patients with normotensive conditions with the methionine-threonine/threonine-threonine genotype had higher LV mass and LVMI (P =.04, for LV mass; P =.14, for LVMI). The association in patients with normotensive conditions was not influenced by blood pressure but was partly confounded by weight.Variation in the angiotensinogen gene was modestly associated with LV mass independently of covariates in patients with hypertensive conditions. The direction of the association was opposite to that observed in patients with normotensive conditions, probably because of the influence of other risk factors or antihypertensive medication use or both.

Published
2002

6. Left Ventricular Systolic Dysfunction in a Biracial Sample of Hypertensive Adults

Author

Albert Oberman, Dalane W. Kitzman, Donna K. Arnett, Vittorio Palmieri, Dawn Fishman, Mary Paranicas, Paul N. Hopkins, Richard B. Devereux, D.C. Rao, Jonathan N. Bella, and Derek Morgan

Subjects
medicine.medical_specialty, education.field_of_study, Creatinine, Ejection fraction, business.industry, Population, Diastole, medicine.disease, Pulse pressure, chemistry.chemical_compound, Endocrinology, chemistry, Internal medicine, Internal Medicine, medicine, Cardiology, Uric acid, Myocardial infarction, education, business, Body mass index
Abstract

To determine the prevalence and correlates of left ventricular systolic dysfunction in hypertensive patients in a biracial population-based sample, clinical evaluation and echocardiography were performed in 2086 participants in the Hypertension Genetic Epidemiology Network (HyperGEN) examination; 86% had normal ejection fraction (>54%), 10% had mild ventricular dysfunction (ejection fraction 41% to 54%), and 4% had severe ventricular dysfunction (ejection fraction ≤40%). Prevalences of mild and severe ventricular dysfunction were higher in men than women (14% versus 8% and 7% versus 3%, P P =0.07). Patients with severe ventricular dysfunction were older than those with mild dysfunction or normal function (mean, 58 versus 54 and 54 years, respectively; P =0.005) and had higher mean creatinine (1.20 versus 1.05 and 1.00 mg/dL) and uric acid (6.9 versus 6.3 and 6.1 mg/dL) levels (both P 2.7 ) and lower relative wall thickness (0.31 versus 33 and 0.35; all P P

Published
2001

7. Preface to Second Edition

Author

C. Charles Gu and D.C. Rao

Subjects
Genetic dissection, Graduate students, Genetic epidemiology, education, Engineering ethics, Biology, humanities, Human genetics
Abstract

Publisher Summary This chapter provides preface of the second edition of the book, “Genetic Dissection of Complex Traits.” This volume contains 25 chapters, divided into 5 sections. This volume can be used as a standard reference by a wide audience of pre- and postdoctoral scientists, methodologists who seek an overview of some of the latest developments in this area, and, most importantly, the scores of investigators who seek to evaluate the genetic basis of complex traits. It can be used as a reference book for upper-level undergraduate students, as well as a textbook for graduate students majoring in quantitative aspects of human genetics or in genetic epidemiology. Genetic dissection of complex traits continues to be the greatest challenge in genetics. However, the future looks more promising and exciting than ever before.

Published
2008

10. Familial resemblance of adiposity-related parameters: results from a health check-up population in Taiwan

Author

Der-Min Wu, Nain-Feng Chu, D.C. Rao, P.-K. Sung, Y. Hong, and C.-A. Sun

Subjects
Gerontology, Epidemiology, media_common.quotation_subject, Population, Taiwan, Body Mass Index, Waist–hip ratio, Medicine, Humans, Obesity, Sibling, education, media_common, Adiposity, education.field_of_study, Daughter, business.industry, Waist-Hip Ratio, nutritional and metabolic diseases, Family aggregation, Heritability, medicine.disease, business, Body mass index, Demography
Abstract

The mechanisms of obesity is still unclear, however, genetic and environmental factors are two major possible causes of obesity. The purpose of this study was to assess the degree of familial resemblance of different obesity-related parameters in a health check-up population in Taiwan. We measured body mass index (BMI), waist-to-hip ratio (WHR) and percentage of body fat (BFAT) anthropometrics in 1724 members of 431 families participating in the MJ Health Screening program. Each family contributed four members, i.e. father, mother, son, and daughter. All the participants were free from coronary heart disease, hypertension, diabetes, dyslipidemia, and generally in good health. The degree of familial aggregation was measured by heritability that was calculated based on age-adjusted familial (parent-offspring, sibling, spouse) correlations. The maximal heritability estimates were 39, 30 and 35% for BMI, WHR and BFAT, respectively. For WHR, the correlation between spouses was not significant and the heritability appears to be predominantly due to genetic causes. Furthermore, for BMI and BFAT, the spouse correlations were 0.08 and 0.11, respectively. The heritabilities for BMI and BFAT were mostly explained by genetic factors and familial environmental factors such as dietary habits or physical activity. The familial resemblance of various obesity-related parameters was moderate in a health check-up population in Taiwan. While the heritability for WHR appears to be mainly due to genetic factors, the familial resemblance for BMI and percentage of BFAT may involve both genetic and familial environmental factors.

Published
2003

11. Linkage of left ventricular contractility to chromosome 11 in humans: The HyperGEN Study

Author

Larry D. Atwood, Donna K. Arnett, Andrew T. DeWan, Richard B. Devereux, Albert Oberman, Dalane W. Kitzman, Paul N. Hopkins, and D.C. Rao

Subjects
Male, medicine.medical_specialty, Heart disease, Genotype, Genetic Linkage, Chromosomes, Human, Pair 22, Heart Ventricles, Black People, Locus (genetics), Genetic determinism, White People, Contractility, Quantitative Trait, Heritable, Genetic linkage, Internal medicine, Internal Medicine, medicine, Humans, Chromosomes, Human, Pair 12, business.industry, Genome, Human, Chromosomes, Human, Pair 11, Hypertrophic cardiomyopathy, Chromosome Mapping, Middle Aged, medicine.disease, Myocardial Contraction, Endocrinology, Phenotype, Echocardiography, Heart failure, Hypertension, Female, Lod Score, business, Chromosome 22, Microsatellite Repeats
Abstract

Impaired left ventricular (LV) contractility is a major cause of cardiovascular death, especially congestive heart failure. The identification of susceptibility genes that contribute to impaired LV contractility may uncover mechanisms underlying LV contractile impairment and the development of congestive heart failure. The Hypertension Genetic Epidemiology Network (HyperGEN) collected echocardiographic measurements of myocardial contractility in a large biethnic sample of hypertensive siblings (390 blacks and 398 whites in 179 and 165 sibships, respectively). All participants expressed hypertension before age 60 years, and the mean age of siblings was 52 years in blacks and 61 years in whites. We adjusted myocardial contractility for gender, age, and age 2 , and we calculated standardized residuals separately for men and women in both ethnic groups. We conducted multipoint variance components linkage analysis using GENEHUNTER2 and 387 anonymous markers (CHCL8 marker set). We found evidence for significant linkage to a microsatellite marker, D11S1993 (lod, 3.93 in blacks), ≈54 cM from the tip of the short arm of chromosome 11, that accounted for 72% of the phenotypic variation in LV contractility. A chromosome 22 locus showed suggestive evidence for linkage (lod, 2.83 in whites and 1.15 in blacks). The chromosome 11 peak coincides with the region containing myosin-binding protein C. Mutations in this gene are linked to familial hypertrophic cardiomyopathy. Our results show strong evidence for linkage of a region of chromosome 11 with LV contractility in blacks and suggest that an important gene for impaired LV contractility is harbored in this region.

Published
2001

12. Relationship between left ventricular diastolic relaxation and systolic function in hypertension: The Hypertension Genetic Epidemiology Network (HyperGEN) Study

Author

Vittorio Palmieri, Steven C. Hunt, Albert Oberman, Jennifer E. Liu, Richard B. Devereux, Donna K. Arnett, Dalane W. Kitzman, Paul N. Hopkins, Jonathan N. Bella, and D.C. Rao

Subjects
Adult, Male, medicine.medical_specialty, Systolic hypertension, Systole, Heart Ventricles, Population, Diastole, Ventricular Function, Left, Predictive Value of Tests, Internal medicine, Internal Medicine, Medicine, Humans, education, End-systolic volume, education.field_of_study, Ejection fraction, business.industry, Stroke Volume, Middle Aged, medicine.disease, Blood pressure, Echocardiography, Hypertension, Cardiology, Female, Isovolumic relaxation time, business
Abstract

The relation of impaired left ventricular relaxation, as measured by prolonged isovolumic relaxation time, to ventricular systolic function in hypertension remains uncertain in population-based samples. In the Hypertension Genetic Epidemiology Network (HyperGEN) Study, echocardiograms were analyzed in 1457 hypertensive participants without diabetes, ≥2+ valvular regurgitation, or coronary disease. Impaired relaxation (isovolumic relaxation time >100 ms) was present in 219 (15%) of the participants; they were older and had higher arterial pressure than did those with normal relaxation. Ventricular chamber size, wall thicknesses, mass, and relative wall thickness were greater, and stress-corrected midwall shortening and end-systolic stress/end-systolic volume index were lower with impaired relaxation than with normal relaxation time. Fractional shortening and ejection fraction did not differ between the groups. In logistic regression, the likelihood of prolonged isovolumic relaxation time decreased with higher stress-corrected midwall shortening (odds ratio, 0.97%; 95% confidence interval, 0.96 to 0.99), independently of age, heart rate, and ventricular mass. Neither ejection fraction nor the end-systolic stress/end-systolic volume index was independently related to isovolumic relaxation time. In hypertension, impaired left ventricular relaxation parallels ventricular midwall dysfunction but not systolic chamber function. Whether combined diastolic and systolic dysfunction identifies hypertensive patients at especially high risk of cardiovascular events requires further study.

Published
2001

13. Familial resemblance in fatness and fat distribution

Author

Peter T., Katzmarzyk, Robert M., Malina, Louis, Pérusse, Treva, Rice, Michael A., Province, D.C., Rao, and Claude, Bouchard

Abstract

The purpose of the study was to estimate the degree of familial resemblance in anthropometric indicators of fatness and fat distribution. The sample consisted of 327 Caucasian participants from 102 nuclear families. Indicators of fatness included the body mass index (BMI), the sum of six skinfolds (SF6: triceps + biceps + medial calf + subscapular + suprailiac + abdominal), and waist circumference (WAIST), while indicators of fat distribution included WAIST adjusted for BMI (WAIST(ADJ)), the trunk-to-extremity skinfold ratio, adjusted for SF6 (TER(ADJ)), and the first principal component of skinfolds, adjusted for the mean skinfold of the individual (PC1). A general familial correlation model was fit to the data, and a series of nested reduced models were also fit so as to test hypotheses about familial resemblance. The hypothesis of no familial resemblance (all familial correlations are zero) was rejected for all phenotypes, indicating that fatness and fat distribution aggregate within families. For the three indicators of fatness (BMI, SF6, and WAIST), the sibling and parent-offspring correlations were significant. Further, there were no sex or generation differences in the familial correlations. For the three indicators of fat distribution (TER(ADJ), WAIST(ADJ), and PC1), there was no parent-offspring resemblance; sibling resemblance was significant for TER(ADJ) and PC1. Further, spouse resemblance was not significant for WAIST(ADJ), but was for TER(ADJ) and PC1. For both WAIST(ADJ) and PC1 there were significant sex differences in the familial correlations. A combination of models including no sex or generation differences and no spouse resemblance was the most parsimonious model for BMI, SF6, and TER(ADJ). The environmental model (all correlations equal) was the most parsimonious for WAIST, the model of no sibling resemblance was the most parsimonious for WAIST(ADJ), and the model of no spousal resemblance was the most parsimonious for PC1. Estimates of maximal heritability range from 46-60% for fatness and from 29-48% for fat distribution, independent of overall fatness, suggesting that in this sample the heritability of fatness is greater than that for fat distribution. Further, the pattern of correlations, which generally includes no spousal resemblance but significant parent-offspring and sibling correlations, suggests the role of genes in explaining at least part of the heritability. Am. J. Hum. Biol. 12:395-404, 2000. Copyright 2000 Wiley-Liss, Inc.

Published
2001

14. Major gene effect on subcutaneous fat distribution in a sedentary population and its response to exercise training: The HERITAGE Family Study

Author

Ping, An, Treva, Rice, Ingrid B., Borecki, Louis, Pérusse, Jacques, Gagnon, Arthur S., Leon, James S., Skinner, Jack H., Wilmore, Claude, Bouchard, and D.C., Rao

Abstract

Complex segregation analysis of baseline subcutaneous fat distribution and the change in response to exercise training (post-training minus baseline indices) was performed in a sample of 482 individuals from 99 Caucasian families who participated in the HERITAGE Family Study. The sum of skinfold (SF) thicknesses at eight sites, and the waist and hip circumferences were measured at baseline and after completing a 20-week exercise training program. The trunk-to-extremity ratio (TER) was calculated by dividing the sum of skinfold thicknesses at four trunk sites (subscapular + suprailiac + abdominal + midaxillary) by the sum of skinfold thicknesses at four extremity sites (triceps + biceps + medial calf + thigh). While SF was used to assess total subcutaneous adiposity, TER and the ratio of the waist-to-hip circumferences (WHR) were used to characterize subcutaneous fat distribution. Baseline TER and WHR were age-adjusted and age-SF-adjusted within four sex-by-generation groups. The changes of SF, TER, and WHR in response to training were adjusted for age effects alone and for the effects of age and baseline values. Baseline SF was influenced by a multifactorial component (30%) plus a major effect that may be environmental in origin accounting for 47% of the variance. Baseline TER was influenced by a multifactorial component (18%) and a major codominant gene (q(2) = 0.10), which accounted for 56% of the variance. The major gene effect was independent of total subcutaneous adiposity. Baseline WHR was regulated by a major codominant gene (q(2) = 0.15), which accounted for 48% of the variance. However, this major gene effect for baseline WHR should be interpreted with caution, given the estimates of the tau's under the general model. No familial effect was found for the changes in response to training for these subcutaneous adiposity and fat distribution phenotypes. Am. J. Hum. Biol. 12:600-609, 2000. Copyright 2000 Wiley-Liss, Inc.

Published
2001

15. Preface

Author

D.C. Rao and M.A. Province

Published
2001

16. Genome-wide search for genes related to the fat-free body mass in the Québec family study

Author

Sonia Roy, Michel Lacaille, Yvon C. Chagnon, Claude Bouchard, Michael A. Province, Louis Pérusse, D.C. Rao, Monique Chagnon, My Anh Ho-Kim, Ingrid B. Borecki, and Treva Rice

Subjects
Adult, Genetic Markers, Male, medicine.medical_specialty, Candidate gene, Genetic Linkage, Endocrinology, Diabetes and Metabolism, Biology, Polymerase Chain Reaction, Genetic determinism, Centimorgan, Endocrinology, Internal medicine, medicine, Humans, Insulin-like growth factor 1 receptor, Aged, Genetics, Chromosomes, Human, Pair 15, Autosome, Genome, Human, Body Weight, Quebec, DNA, Middle Aged, medicine.disease, Melanocortin 4 receptor, Phenotype, Sarcopenia, Lean body mass, Body Composition, Female, Chromosomes, Human, Pair 18, Chromosomes, Human, Pair 7
Abstract

Fat-free mass (FFM) consists mostly of skeletal muscle and bone tissues, and identification of the genes and molecular mechanisms involved in the control of FFM would have implications for the understanding of sarcopenia and potentially osteoporesis associated with aging, as well as the response to starvation, refeeding, anorexia, and any other conditions in which lean body mass is important. A genome-wide search for genes related to body leanness has been completed in the Quebec Family Study (QFS). Microsatellite markers (N = 292) from the 22 autosomal chromosomes were typed. The mean spacing of the markers was 11.9 centimorgans (cM) (range

Published
2000

17. Subject Index Vol. 29, 2009

Author

Chi-Chih Hung, Martin Tepel, Minoru Takemoto, Alexandra Scholze, Toshimitsu Niwa, Hironori Nakamura, Domenic J. Reda, Peter Bárány, Hyun Ju Kim, Christina Thies, See-Hyoung Park, Sybille Franke, Zohra Tumur, Timo Pikkarainen, Daniel R. Martin, Jeffrey B. Kopp, Rachelle Bross, Nosratola D. Vaziri, Antje Wittstock, Jennifer Zitterkoph, Paul Winters, Mei-Chuan Kuo, Gunter Wolf, Walter Zidek, Cheryl A. Winkler, Tejas V. Patel, Kamyar Kalantar-Zadeh, Jonas Axelsson, Karl Tryggvason, James A. Sloand, Abdul Rashid Qureshi, Jessica L. Elder, Jenny Norlin, Susan G. Fisher, Cheuk-Chun Szeto, Ying Sun, William S. Beckett, John H. Eckfeldt, Mai-Szu Wu, Peter Stenvinkel, Angie Hirter, Xiaoyan Zhou, Heng Jung Hsu, Qunying Guo, S. Pinnelli, Timothy P. Ryan, Hugo Abensur, Deborah Benner, Kevin C. Abbott, M. Cignarelli, D. Camarchio, Nobushige Tanaka, Eduardo Lyra de Queiroz, Geraldo Lorenzi-Filho, Christiane Rüster, Chih-Ken Chen, Jaakko Patrakka, Liqun He, Joel D. Kopple, Ka-Bik Lai, Juhi Pithia, Ajay K. Singh, Eduardo Slatopolsky, Rosilene M. Elias, Kai-Ming Chow, Neal P. Das, Mark Leppert, L. Gesualdo, Sunna Snaedal, Hung-Chun Chen, Steven C. Hunt, Kam-Tao Philip Li, S. Fariello, O. Lamacchia, Jane Finch, Fernand Mac-Moune Lai, Olof Heimbürger, João Egidio Romão-Junior, Wan-Chun Liu, Tzvetanka Bondeva, Pamela J. Hicks, Frank P. Hurst, Guillem Genové, James Tacci, Hiroshi Yamamoto, Barry I. Freedman, Eric A. Elster, Mohamed Cheikhalfraj, Chih-Hung Lee, Mehdi Rambod, Carl D. Langefeld, Rahul M. Jindal, Edward D. Frohlich, George W. Nelson, Edward M. Falta, Csaba P. Kovesdy, Masanori Tokumoto, Dinko Susic, Katarina Truvé, Shang-Jyh Hwang, Jasmin Divers, Gang Wang, Masahide Mizobuchi, Sai Ram Keithi-Reddy, D.C. Rao, Christer Betsholtz, G. Stallone, Wolfgang Pommer, Jin Young Park, Robert T. Neff, Bengt Lindholm, Ching-Ha Bonnie Kwan, Manuel Carlos Martins Castro, Robert H. Weiss, and James S. Kaufman

Subjects
Index (economics), Nephrology, business.industry, Statistics, Medicine, Subject (documents), business
Published
2009

19. Response

Author

Claude Bouchard, Arthur S. Leon, D.C. Rao, James S. Skinner, and Jack H. Wilmore

Subjects
Anthropology, Genetics, Anatomy, Ecology, Evolution, Behavior and Systematics
Published
1998

20. ATPIII-defined metabolic syndrome is associated with prevalence of LV hypertrophy in white, but not in African American, treated hypertensives: the hypergen study

Author

Paul N. Hopkins, Dalane W. Kitzman, Jonathan N. Bella, Giovanni de Simone, Albert Oberman, Jennifer E. Liu, Richard B. Devereux, Donna K. Arnett, D.C. Rao, and Marcello Chinali

Subjects
African american, medicine.medical_specialty, White (horse), Endocrinology, business.industry, Internal medicine, Internal Medicine, medicine, Cardiology, Metabolic syndrome, LV hypertrophy, business, medicine.disease
Published
2003

21. Contents, Vol. 22, 1978

Author

N.E. Morton, P. Pierce, K. Simola, C.E. Wright, E.J. Yunis, M.E. Chandler, H. Vriesendorp, B.J.B. Keats, C.J. Sherr, K. Bender, R.E. Magenis, H. Oie, B.B. Knowles, J.M. Luciani, M.P. Cowmeadow, I.L. Hansteen, M. Bobrow, G.A. Koch, M. Prensky, P.A. Lalley, N. Shimizu, E.A. Nichols, J. Garver, K. Hirschhorn, A. Brøgger, A.F. Gazdar, S. Hempfling, L.C. Yu, B. Pernis, R. Mausner, S. Leupe-de Smit, R.C.P. Go, A. Westerveld, L. R. Weitkamp, K.E. Toomey, D. Borgaonkar, S. Piomelli, D. Bootsma, T. Campana, E.W. Lovrien, O.J. Miller, H.J. Cooke, F.T. Kao, D.A. Aitken, S. Burgess, L.L. Haley, Y. Boyd, A. Mayerová, T.B. Shows, H.J. Evans, J. Fraisse, K.-H. Grzeschik, V.M. Regina, K.C. Atwood, L.M.M. Wijnen, Liao Law, H.-H. Ropers, M.A. Ferguson-Smith, M.A. Pellegrino, T. Gedde-Dahl, V.A. McKusick, A.C. Leary, J. H. Olving, M.G. Byers, D. Swallow, K.M. Overton, W.F. Witterland, J. Hemmerling, S.J. Funderburk, A. de la Chapelle, N.R. Mendell, U. Francke, Veronica van Heyningen, A.F. Naylor, I.W. Craig, A. Heiberg, R.S. Lemons, J.E. Gray, E. Herbschleb-Voogt, J.J. Yunis, D.B. Amos, C.K. Eun, J.L. Hamerton, L. U. Lamm, N. Oliver, S. Goodnight, F. Pellett, T.M. Dijksman, J.M. Vance, R.E. Eisenman, P. Rubinstein, A. Bratlie, G.A.P. Bruns, V. Kirton, R. Roos, D.L. Slate, M.C. Yoshida, D.L. George, R.C. Schwartz, K.E. Buckton, A.S. Henderson, R. Jonassen, J.A. Robinson, P.L. Pearson, M. Hultén, E. Solomon, A.E. Greene, L.Y. Wang, R. Lange, S. Brown, M.L. Schroeder, P. Karli, A. Krüger, J.M. Robert, B. Lauras, J. Chamberlin, A. Shalev, J. Ott, B.J. Mintz, Elizabeth B. Robson, Per Teisberg, N. Tanigaki, P. M. Conneally, S. Rosenfeld, A.S. Baim, M.L. Rivas, J.A. Brown, R. Johannsmann, N. Suciu-Foca, R. Mierau, T.T. Puck, C.G. Palmer, S.J. Jeremiah, D. Warburton, M. Devictor-Vuillet, J.A. Norton, T. Ho, J.E. Noades, F. Varricchio, E.H.Y. Chu, B. Carritt, R. Schwab, I. Balazs, J. Reiss, C.N. Fear, S. Povey, Erik Thorsby, A. Siverts, D.W. Ball, W. Stanley, L.R. Weitkamp, M.E. Duncan, C. Jones, K. Willecke, S. Philipps, R. Moreland, D.C. Rao, E. Tolley, T. Philip, E. Johnston, M. Monteba-van Heuvel, A.D. Merritt, T.H. Roderick, R.L. Eddy, S. Arias, R.A. Fisher, M.A. Craft, J.H. Edwards, M.C. Sparkes, N.C. Sun, L. Korsnes, D.A. Meyers, M.Y. Tsai, A.W. Johnston, A. Estop, B.M. Turner, K. Berg, S. Guttormsen, W.G. Burgerhout, A.P. Goggin, T. Mohandas, W.K. Stanford, C.W. Bazinet, M. Siniscalco, R.H. Lindenbaum, H.P. Klinger, W.S. Volkers, J. Gavin, K.K. Namboodiri, M.T. Davisson, P.J. McAlpine, W.R.T. Los, M. Meisler, L.J. Donald, F.H. Ruddle, W. Bauch, Timothy A. Donlon, C.R.Y. Sun, R. Bigley, R.S. Sparkes, H. Kaita, P.S. Gerald, E.R. Giblett, I. Berczi, R.C. Elston, S.J. O’Brien, C.T. Falk, L. Scrafford-Wolff, M. Smith, M.K. Fagerhol, J. de Witt, S. Rowe, D. Cox, E.S. Seravalli, T. Borun, M. Lewis, R. Saisson, M.A. Pericak-Vance, R.T. Taggart, R.D.G. McKay, M. Mota, W. R. Mayr, Matthew Parks, F. Freycon, Y. Shimizu, B. Hellkuhl, D.P. Aden, C.A. Slaughter, J.E. Anderson, E. Lovrien, R.M. Denney, N. Lamvik, J. Parekh, B.P. Dorman, A.P.M. Jongsma, M.A. Nijman, C. Verma, J. Wood, M.J. Champion, R. Sanger, A. Bennick, P.L. Yu, A.F. Wilson, W.L. Marsh, L. Pajunen, H. Hameister, B.A. Doppert, J.J. Garver, J.R. Sawyer, P. Meera Khan, P.J.L. Cook, Bjørnar Olaisen, R.C. Karn, J.D. Minna, J.D. Shulkin, B.M. Page, P.M. Sinet, B. Sykes, E.M. Helveston, C.W.H. Partridge, M. Blumenthal, P. Szabo, and E.A. Azen

Subjects
Botany, Genetics, Biology, Molecular Biology, Genetics (clinical)
Published
1978

22. Economic growth and equity in the Republic of Korea

Author

D.C. Rao

Subjects
Macroeconomics, Economics and Econometrics, Equity (economics), Economic expansion, Sociology and Political Science, National accounts, Geography, Planning and Development, Development, Per capita income, Income distribution, Capital deepening, Economic interventionism, Development economics, Economics, Productivity
Abstract

The structural characteristics and specific interventionist policies in Korea and their relationship to employment trends are examined. The relatively good performance of Korea in the distribution of the benefits of growth is principally the result of the growth strategy, which relies heavily on exports and results in the expansion of labor-intensive manufacturing activities. The government also has concentrated on reducing rural-urban disparities in household income with particular attention to grain pricing. Although Korea has excelled in combining rapid growth with a reasonably wide distribution of the benefits of growth, some serious problems remain. Demographic factors tend to be less favorable for achieving a rapid improvement in equity. The rate of growth of export demand will probably slow down significantly. The rapid growth in productivity cannot be maintained. Recommendations are made to mobilize resources, facilitate new technology, and encourage the absorption of labor. If a growth rate of over 9 percent per annum can be sustained and special measures taken, Korea can look forward to full employment and the elimination of absolute poverty before the end of the next decade. Economic data are included.

Published
1978

24. Subject Index Vol. 22, 1978

Author

S.J. Funderburk, J.E. Gray, G.A. Koch, L. Korsnes, A.S. Henderson, W.R.T. Los, D.A. Meyers, J.D. Minna, Per Teisberg, J.D. Shulkin, B.M. Page, M.C. Yoshida, K.E. Buckton, M.C. Sparkes, A.P. Goggin, M.L. Rivas, P.S. Gerald, K. Simola, C.E. Wright, W.K. Stanford, J.A. Brown, R.C.P. Go, L. Scrafford-Wolff, P.M. Sinet, D.C. Rao, E.J. Yunis, A. Westerveld, L. R. Weitkamp, B. Sykes, M. Bobrow, N. Oliver, H.-H. Ropers, M.A. Ferguson-Smith, D. Borgaonkar, S. Piomelli, D. Bootsma, C.W. Bazinet, A.F. Wilson, H. Hameister, P.J.L. Cook, E. Herbschleb-Voogt, J.J. Yunis, P. Szabo, S. Philipps, W. R. Mayr, T.B. Shows, E.A. Azen, R.C. Schwartz, J.M. Vance, S. Leupe-de Smit, D. Swallow, A.C. Leary, Bjørnar Olaisen, R.C. Karn, Y. Shimizu, B.J.B. Keats, E. Solomon, M.L. Schroeder, T. Gedde-Dahl, O.J. Miller, V. Kirton, J. H. Olving, S. Brown, R. Roos, D. Cox, F. Pellett, L.Y. Wang, Timothy A. Donlon, R.E. Magenis, E.M. Helveston, N.C. Sun, A. de la Chapelle, J.M. Luciani, A. Heiberg, R.S. Lemons, D.L. George, C.R.Y. Sun, R.D.G. McKay, R.M. Denney, N. Lamvik, A.S. Baim, R. Schwab, I. Balazs, N.E. Morton, L. Pajunen, M. Blumenthal, J.R. Sawyer, Elizabeth B. Robson, R.E. Eisenman, M. Prensky, P.A. Lalley, K.M. Overton, T.M. Dijksman, L.C. Yu, J.A. Robinson, L.M.M. Wijnen, H. Kaita, R.C. Elston, S.J. O’Brien, J. Garver, M.A. Nijman, M. Monteba-van Heuvel, P.L. Pearson, S. Povey, Erik Thorsby, B. Lauras, P. M. Conneally, V.A. McKusick, E. Tolley, K. Willecke, A.D. Merritt, R. Moreland, P. Meera Khan, P. Pierce, T.H. Roderick, M.Y. Tsai, R. Johannsmann, T. Campana, A. Brøgger, E.W. Lovrien, R.L. Eddy, N. Suciu-Foca, C.G. Palmer, C. Jones, A.F. Gazdar, A. Shalev, M.K. Fagerhol, E. Johnston, J. Reiss, C.N. Fear, S. Burgess, L.L. Haley, S. Hempfling, W.S. Volkers, J. Gavin, Liao Law, Y. Boyd, A. Mayerová, J.H. Edwards, M.G. Byers, W. Stanley, L.R. Weitkamp, M.E. Duncan, H.J. Evans, L.J. Donald, B. Hellkuhl, F.H. Ruddle, I.L. Hansteen, B.M. Turner, I.W. Craig, K.-H. Grzeschik, T. Mohandas, A. Siverts, D.W. Ball, K.C. Atwood, R. Bigley, L. U. Lamm, R.S. Sparkes, M. Siniscalco, S. Arias, R.A. Fisher, M. Mota, E.R. Giblett, C.T. Falk, S. Guttormsen, N.R. Mendell, K. Hirschhorn, M. Smith, H. Oie, M.P. Cowmeadow, F.T. Kao, J. de Witt, N. Shimizu, E.A. Nichols, E.S. Seravalli, D.A. Aitken, R. Mausner, M. Hultén, M. Lewis, R. Saisson, A. Bratlie, A.E. Greene, P. Karli, J. Chamberlin, M.T. Davisson, P.J. McAlpine, C.W.H. Partridge, I. Berczi, W.F. Witterland, Veronica van Heyningen, B.P. Dorman, A.P.M. Jongsma, P. Rubinstein, B.B. Knowles, C. Verma, J. Wood, M.J. Champion, B. Pernis, R. Sanger, K.E. Toomey, A. Bennick, P.L. Yu, W.L. Marsh, V.M. Regina, B.A. Doppert, J.J. Garver, U. Francke, J. Fraisse, M.E. Chandler, G.A.P. Bruns, H. Vriesendorp, S. Rowe, A. Krüger, J.M. Robert, B.J. Mintz, K. Bender, R. Lange, T. Borun, J.A. Norton, T. Ho, J.E. Noades, M.A. Pericak-Vance, R.T. Taggart, N. Tanigaki, M.A. Craft, K. Berg, Matthew Parks, F. Freycon, D.P. Aden, C.A. Slaughter, H.J. Cooke, J.E. Anderson, E. Lovrien, A.W. Johnston, A. Estop, J. Parekh, W.G. Burgerhout, M.A. Pellegrino, J. Hemmerling, A.F. Naylor, J.L. Hamerton, S. Goodnight, D.B. Amos, C.K. Eun, D.L. Slate, R. Jonassen, J. Ott, R. Mierau, T.T. Puck, D. Warburton, M. Devictor-Vuillet, C.J. Sherr, R.H. Lindenbaum, H.P. Klinger, K.K. Namboodiri, M. Meisler, S. Rosenfeld, F. Varricchio, E.H.Y. Chu, B. Carritt, T. Philip, W. Bauch, and S.J. Jeremiah

Subjects
Index (economics), Statistics, Genetics, Subject (documents), Biology, Molecular Biology, Genetics (clinical)
Published
1978

25. Contents, Vol. 20, 1970

Author

A.E. Mourant, T. Olivecrona, M.J. Godber, M.K. Bhasin, A.W. Eriksson, Richard L. Jantz, Francis E. Johnston, J.B.C. Azevedo, A. Pal, Olle Hernell, Wolfgang Lehmann, K.M. Kensinger, Eleidi A. Chautard, M. Modai, B. Bonné, A. Szeinberg, D.C. Rao, L. Beckman, Johan Fellman, Shulamith Tomashewsky, B.G. Woodhead, Newton Freire-Maia, D. Tills, S. Ashbel, P. Teisberg, B. Arce-Gomez, Henrik Forsius, and G.F. Walker

Subjects
Genetics, Genetics (clinical)
Published
1970

26. Joint Distribution of z Transformations Estimated from the Same Sample

Author

D.C. Rao

Subjects
Multivariate statistics, Statistics as Topic, Mathematical analysis, Matrix t-distribution, Multivariate normal distribution, Sampling Studies, Normal-Wishart distribution, Genetics, Population, Transformation, Genetic, Joint probability distribution, Scatter matrix, Genetics, Humans, Matrix normal distribution, Mathematics, Genetics (clinical), Multivariate stable distribution
Abstract

When correlations are estimated by maximum likelihood method from the same sample, Fisher's z transformations of the correlations (as well as the sample correlations themselves) are shown to be asymptotically distributed as multivariate normal with appropriate mean and dispersion matrix.

Published
1979

27. Index rerum Vol. 20

Author

L. Beckman, D. Tills, Johan Fellman, A.W. Eriksson, B.G. Woodhead, M.K. Bhasin, Wolfgang Lehmann, A. Szeinberg, J.B.C. Azevedo, P. Teisberg, S. Ashbel, Newton Freire-Maia, M. Modai, Olle Hernell, Henrik Forsius, Shulamith Tomashewsky, Richard L. Jantz, G.F. Walker, D.C. Rao, M.J. Godber, K.M. Kensinger, A. Pal, A.E. Mourant, Eleidi A. Chautard, B. Bonné, B. Arce-Gomez, Francis E. Johnston, and T. Olivecrona

Subjects
Genetics, Genetics (clinical)
Published
1970

28. Characteristics of a linkage heterogeneity test

Author

N. E. Morton, D.C. Rao, and Bronya J.B. Keats

Subjects
Linkage (software), Genetics, Recombination, Genetic, Genetic Techniques, Genetic Linkage, Chromosome Mapping, Humans, Biology, Molecular Biology, Genetics (clinical), Test (assessment)
Published
1978

29. Family resemblance for glucose tolerance in a Melanesian population, the Tolai

Author

K. Bhatia, D.C. Rao, G. Koki, H. King, Andrew M. Collins, and Paul Zimmet

Subjects
Adult, Blood Glucose, Male, Adolescent, Genotype, Population, Population genetics, Family resemblance, Biology, Body Mass Index, Genetics, medicine, Humans, Obesity, Sibling, education, Path analysis (statistics), Child, Genetics (clinical), Aged, education.field_of_study, Glucose tolerance test, medicine.diagnostic_test, Heritability, Middle Aged, Skinfold Thickness, Phenotype, Diabetes Mellitus, Type 2, Trait, Female, Melanesia
Abstract

Path analysis of family resemblance for plasma glucose concentration, 2 h after an oral glucose challenge, failed to detect significant genetic heritability. There were no intergenerational differences and marital resemblance was moderate. Over one-third of sibling environmental similarity was due to non-inherited factors. Cultural inheritance was very strong, tending to mimic genetic inheritance, and cultural heritability was considerable. Measures of obesity were included in the environmental index, an estimate of familial environment, in this analysis, for comparability with previous studies. Since obesity appears, in part, to be a heritable trait, in future studies a bivariate approach to family resemblance for both glucose tolerance and obesity could yield important additional insight.

Published
1989

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