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1. Sex differences in vectorcardiogram of African-Americans with and without cardiovascular disease: a cross-sectional study in the Jackson Heart Study cohort

Author

Elsayed Z Soliman, James D Pollard, Kazi T Haq, Katherine J Lutz, Nichole M Rogovoy, Kevin A Paternostro, Joseph Maher, Joao AC Lima, Solomon Musani, and Larisa G Tereshchenko

Subjects
Medicine
Abstract

Objectives We hypothesised that (1) the prevalent cardiovascular disease (CVD) is associated with global electrical heterogeneity (GEH) after adjustment for demographic, anthropometric, socioeconomic and traditional cardiovascular risk factors, (2) there are sex differences in GEH and (3) sex modifies an association of prevalent CVD with GEH.Design Cross-sectional, cohort study.Setting Prospective African-American The Jackson Heart Study (JHS) with a nested family cohort in 2000–2004 enrolled residents of the Jackson, Mississippi metropolitan area.Participants Participants from the JHS with analysable ECGs recorded in 2009–2013 (n=3679; 62±12 y; 36% men; 863 family units). QRS, T and spatial ventricular gradient (SVG) vectors’ magnitude and direction, spatial QRS-T angle and sum absolute QRST integral (SAI QRST) were measured.Outcome Prevalent CVD was defined as the history of (1) coronary heart disease defined as diagnosed/silent myocardial infarction, or (2) revascularisation procedure defined as prior coronary/peripheral arterial revascularisation, or (3) carotid angioplasty/carotid endarterectomy, or (4) stroke.Results In adjusted mixed linear models, women had a smaller spatial QRS-T angle (−12.2 (95% CI −19.4 to -5.1)°; p=0.001) and SAI QRST (−29.8 (−39.3 to −20.3) mV*ms; p

Published
2021
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2. Genome-wide association study of coronary artery calcified atherosclerotic plaque in African Americans with type 2 diabetes

Author

Jasmin Divers, Nicholette D. Palmer, Carl D. Langefeld, W. Mark Brown, Lingyi Lu, Pamela J. Hicks, S. Carrie Smith, Jianzhao Xu, James G. Terry, Thomas C. Register, Lynne E. Wagenknecht, John S. Parks, Lijun Ma, Gary C. Chan, Sarah G. Buxbaum, Adolfo Correa, Solomon Musani, James G. Wilson, Herman A. Taylor, Donald W. Bowden, John Jeffrey Carr, and Barry I. Freedman

Subjects
African Americans, Coronary artery calcified atherosclerotic plaque, Genome-wide association study, Cardiovascular disease, Type 2 diabetes, Genetics, QH426-470
Abstract

Abstract Background Coronary artery calcified atherosclerotic plaque (CAC) predicts cardiovascular disease (CVD). Despite exposure to more severe conventional CVD risk factors, African Americans (AAs) are less likely to develop CAC, and when they do, have markedly lower levels than European Americans. Genetic factors likely contribute to the observed ethnic differences. To identify genes associated with CAC in AAs with type 2 diabetes (T2D), a genome-wide association study (GWAS) was performed using the Illumina 5 M chip in 691 African American-Diabetes Heart Study participants (AA-DHS), with replication in 205 Jackson Heart Study (JHS) participants with T2D. Genetic association tests were performed on the genotyped and 1000 Genomes-imputed markers separately for each study, and combined in a meta-analysis. Results Single nucleotide polymorphisms (SNPs), rs11353135 (2q22.1), rs16879003 (6p22.3), rs5014012, rs58071836 and rs10244825 (all on chromosome 7), rs10918777 (9q31.2), rs13331874 (16p13.3) and rs4459623 (18q12.1) were associated with presence and/or quantity of CAC in the AA-DHS and JHS, with meta-analysis p-values ≤8.0 × 10−7. The strongest result in AA-DHS alone was rs6491315 in the 13q32.1 region (parameter estimate (SE) = −1.14 (0.20); p-value = 9.1 × 10−9). This GWAS peak replicated a previously reported AA-DHS CAC admixture signal (rs7492028, LOD score 2.8). Conclusions Genetic association between SNPs on chromosomes 2, 6, 7, 9, 16 and 18 and CAC were detected in AAs with T2D from AA-DHS and replicated in the JHS. These data support a role for genetic variation on these chromosomes as contributors to CAC in AAs with T2D, as well as to variation in CAC between populations of African and European ancestry.

Published
2017
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3. 4392 Comparative Analysis of Vascular Hemodynamics in a Young Biracial Cohort

Author

Preston Bell, Ervin Fox, Solomon Musani, and Gary Mitchell

Subjects
Medicine
Abstract

OBJECTIVES/GOALS: We investigated hemodynamic measures in young black and white adults below the age of 50 years to identify mechanisms that may predispose blacks to more CVE. METHODS/STUDY POPULATION: We recruited 276 young blacks and white adults in Jackson, MS (mean age: 33 ± 9 years; 70% women; 57% Black;). Participants had clinical and vascular tonometry parameters obtained. Vascular measures included carotid femoral pulse wave velocity, central and peripheral pulse pressure (CPP and PPP), characteristic impedance (Zc), augmentation index, and forward pressure wave. Race-specific characteristic means and proportions were tested using Student’s T- or Chi-square tests. After further sex stratification, significant variation in characteristics among sex within race were tested using nested ANOVA. RESULTS/ANTICIPATED RESULTS: Characteristics of the study group stratified by race were found to be similar. Vascular measures stratified by race revealed blacks to have significantly higher Zc (p = 0.03) and PPP (p = 0.03) than whites. DISCUSSION/SIGNIFICANCE OF IMPACT: In this study of vascular hemodynamics in young black and white participants we found differences in Zc and PPP. Findings suggest that differing relations between proximal aortic diameter and wall stiffness may contribute to the racial disparity in CVE in adults. This finding could offer an explanation to the beneficial effects of treatment modalities that target aortic stiffness in blacks.

Published
2020
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4. Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.

Author

Zari Dastani, Marie-France Hivert, Nicholas Timpson, John R B Perry, Xin Yuan, Robert A Scott, Peter Henneman, Iris M Heid, Jorge R Kizer, Leo-Pekka Lyytikäinen, Christian Fuchsberger, Toshiko Tanaka, Andrew P Morris, Kerrin Small, Aaron Isaacs, Marian Beekman, Stefan Coassin, Kurt Lohman, Lu Qi, Stavroula Kanoni, James S Pankow, Hae-Won Uh, Ying Wu, Aurelian Bidulescu, Laura J Rasmussen-Torvik, Celia M T Greenwood, Martin Ladouceur, Jonna Grimsby, Alisa K Manning, Ching-Ti Liu, Jaspal Kooner, Vincent E Mooser, Peter Vollenweider, Karen A Kapur, John Chambers, Nicholas J Wareham, Claudia Langenberg, Rune Frants, Ko Willems-Vandijk, Ben A Oostra, Sara M Willems, Claudia Lamina, Thomas W Winkler, Bruce M Psaty, Russell P Tracy, Jennifer Brody, Ida Chen, Jorma Viikari, Mika Kähönen, Peter P Pramstaller, David M Evans, Beate St Pourcain, Naveed Sattar, Andrew R Wood, Stefania Bandinelli, Olga D Carlson, Josephine M Egan, Stefan Böhringer, Diana van Heemst, Lyudmyla Kedenko, Kati Kristiansson, Marja-Liisa Nuotio, Britt-Marie Loo, Tamara Harris, Melissa Garcia, Alka Kanaya, Margot Haun, Norman Klopp, H-Erich Wichmann, Panos Deloukas, Efi Katsareli, David J Couper, Bruce B Duncan, Margreet Kloppenburg, Linda S Adair, Judith B Borja, DIAGRAM+ Consortium, MAGIC Consortium, GLGC Investigators, MuTHER Consortium, James G Wilson, Solomon Musani, Xiuqing Guo, Toby Johnson, Robert Semple, Tanya M Teslovich, Matthew A Allison, Susan Redline, Sarah G Buxbaum, Karen L Mohlke, Ingrid Meulenbelt, Christie M Ballantyne, George V Dedoussis, Frank B Hu, Yongmei Liu, Bernhard Paulweber, Timothy D Spector, P Eline Slagboom, Luigi Ferrucci, Antti Jula, Markus Perola, Olli Raitakari, Jose C Florez, Veikko Salomaa, Johan G Eriksson, Timothy M Frayling, Andrew A Hicks, Terho Lehtimäki, George Davey Smith, David S Siscovick, Florian Kronenberg, Cornelia van Duijn, Ruth J F Loos, Dawn M Waterworth, James B Meigs, Josee Dupuis, J Brent Richards, Benjamin F Voight, Laura J Scott, Valgerdur Steinthorsdottir, Christian Dina, Ryan P Welch, Eleftheria Zeggini, Cornelia Huth, Yurii S Aulchenko, Gudmar Thorleifsson, Laura J McCulloch, Teresa Ferreira, Harald Grallert, Najaf Amin, Guanming Wu, Cristen J Willer, Soumya Raychaudhuri, Steve A McCarroll, Oliver M Hofmann, Ayellet V Segrè, Mandy van Hoek, Pau Navarro, Kristin Ardlie, Beverley Balkau, Rafn Benediktsson, Amanda J Bennett, Roza Blagieva, Eric Boerwinkle, Lori L Bonnycastle, Kristina Bengtsson Boström, Bert Bravenboer, Suzannah Bumpstead, Noël P Burtt, Guillaume Charpentier, Peter S Chines, Marilyn Cornelis, Gabe Crawford, Alex S F Doney, Katherine S Elliott, Amanda L Elliott, Michael R Erdos, Caroline S Fox, Christopher S Franklin, Martha Ganser, Christian Gieger, Niels Grarup, Todd Green, Simon Griffin, Christopher J Groves, Candace Guiducci, Samy Hadjadj, Neelam Hassanali, Christian Herder, Bo Isomaa, Anne U Jackson, Paul R V Johnson, Torben Jørgensen, Wen H L Kao, Augustine Kong, Peter Kraft, Johanna Kuusisto, Torsten Lauritzen, Man Li, Aloysius Lieverse, Cecilia M Lindgren, Valeriya Lyssenko, Michel Marre, Thomas Meitinger, Kristian Midthjell, Mario A Morken, Narisu Narisu, Peter Nilsson, Katharine R Owen, Felicity Payne, Ann-Kristin Petersen, Carl Platou, Christine Proença, Inga Prokopenko, Wolfgang Rathmann, N William Rayner, Neil R Robertson, Ghislain Rocheleau, Michael Roden, Michael J Sampson, Richa Saxena, Beverley M Shields, Peter Shrader, Gunnar Sigurdsson, Thomas Sparsø, Klaus Strassburger, Heather M Stringham, Qi Sun, Amy J Swift, Barbara Thorand, Jean Tichet, Tiinamaija Tuomi, Rob M van Dam, Timon W van Haeften, Thijs van Herpt, Jana V van Vliet-Ostaptchouk, G Bragi Walters, Michael N Weedon, Cisca Wijmenga, Jacqueline Witteman, Richard N Bergman, Stephane Cauchi, Francis S Collins, Anna L Gloyn, Ulf Gyllensten, Torben Hansen, Winston A Hide, Graham A Hitman, Albert Hofman, David J Hunter, Kristian Hveem, Markku Laakso, Andrew D Morris, Colin N A Palmer, Igor Rudan, Eric Sijbrands, Lincoln D Stein, Jaakko Tuomilehto, Andre Uitterlinden, Mark Walker, Richard M Watanabe, Goncalo R Abecasis, Bernhard O Boehm, Harry Campbell, Mark J Daly, Andrew T Hattersley, Oluf Pedersen, Inês Barroso, Leif Groop, Rob Sladek, Unnur Thorsteinsdottir, James F Wilson, Thomas Illig, Philippe Froguel, Cornelia M van Duijn, Kari Stefansson, David Altshuler, Michael Boehnke, Mark I McCarthy, Nicole Soranzo, Eleanor Wheeler, Nicole L Glazer, Nabila Bouatia-Naji, Reedik Mägi, Joshua Randall, Paul Elliott, Denis Rybin, Abbas Dehghan, Jouke Jan Hottenga, Kijoung Song, Anuj Goel, Taina Lajunen, Alex Doney, Christine Cavalcanti-Proença, Meena Kumari, Nicholas J Timpson, Carina Zabena, Erik Ingelsson, Ping An, Jeffrey O'Connell, Jian'an Luan, Amanda Elliott, Steven A McCarroll, Rosa Maria Roccasecca, François Pattou, Praveen Sethupathy, Yavuz Ariyurek, Philip Barter, John P Beilby, Yoav Ben-Shlomo, Sven Bergmann, Murielle Bochud, Amélie Bonnefond, Knut Borch-Johnsen, Yvonne Böttcher, Eric Brunner, Suzannah J Bumpstead, Yii-Der Ida Chen, Peter Chines, Robert Clarke, Lachlan J M Coin, Matthew N Cooper, Laura Crisponi, Ian N M Day, Eco J C de Geus, Jerome Delplanque, Annette C Fedson, Antje Fischer-Rosinsky, Nita G Forouhi, Maria Grazia Franzosi, Pilar Galan, Mark O Goodarzi, Jürgen Graessler, Scott Grundy, Rhian Gwilliam, Göran Hallmans, Naomi Hammond, Xijing Han, Anna-Liisa Hartikainen, Caroline Hayward, Simon C Heath, Serge Hercberg, David R Hillman, Aroon D Hingorani, Jennie Hui, Joe Hung, Marika Kaakinen, Jaakko Kaprio, Y Antero Kesaniemi, Mika Kivimaki, Beatrice Knight, Seppo Koskinen, Peter Kovacs, Kirsten Ohm Kyvik, G Mark Lathrop, Debbie A Lawlor, Olivier Le Bacquer, Cécile Lecoeur, Yun Li, Robert Mahley, Massimo Mangino, María Teresa Martínez-Larrad, Jarred B McAteer, Ruth McPherson, Christa Meisinger, David Melzer, David Meyre, Braxton D Mitchell, Sutapa Mukherjee, Silvia Naitza, Matthew J Neville, Marco Orrù, Ruth Pakyz, Giuseppe Paolisso, Cristian Pattaro, Daniel Pearson, John F Peden, Nancy L Pedersen, Andreas F H Pfeiffer, Irene Pichler, Ozren Polasek, Danielle Posthuma, Simon C Potter, Anneli Pouta, Michael A Province, Nigel W Rayner, Kenneth Rice, Samuli Ripatti, Fernando Rivadeneira, Olov Rolandsson, Annelli Sandbaek, Manjinder Sandhu, Serena Sanna, Avan Aihie Sayer, Paul Scheet, Udo Seedorf, Stephen J Sharp, Beverley Shields, Gunnar Sigurðsson, Eric J G Sijbrands, Angela Silveira, Laila Simpson, Andrew Singleton, Nicholas L Smith, Ulla Sovio, Amy Swift, Holly Syddall, Ann-Christine Syvänen, Anke Tönjes, André G Uitterlinden, Ko Willems van Dijk, Dhiraj Varma, Sophie Visvikis-Siest, Veronique Vitart, Nicole Vogelzangs, Gérard Waeber, Peter J Wagner, Andrew Walley, Kim L Ward, Hugh Watkins, Sarah H Wild, Gonneke Willemsen, Jaqueline C M Witteman, John W G Yarnell, Diana Zelenika, Björn Zethelius, Guangju Zhai, Jing Hua Zhao, M Carola Zillikens, DIAGRAM Consortium, GIANT Consortium, Global B Pgen Consortium, Ingrid B Borecki, Pierre Meneton, Patrik K E Magnusson, David M Nathan, Gordon H Williams, Kaisa Silander, Stefan R Bornstein, Peter Schwarz, Joachim Spranger, Fredrik Karpe, Alan R Shuldiner, Cyrus Cooper, Manuel Serrano-Ríos, Lars Lind, Lyle J Palmer, Paul W Franks, Shah Ebrahim, Michael Marmot, W H Linda Kao, Peter Paul Pramstaller, Alan F Wright, Michael Stumvoll, Anders Hamsten, Procardis Consortium, Thomas A Buchanan, Timo T Valle, Jerome I Rotter, Brenda W J H Penninx, Dorret I Boomsma, Antonio Cao, Angelo Scuteri, David Schlessinger, Manuela Uda, Aimo Ruokonen, Marjo-Riitta Jarvelin, Leena Peltonen, Vincent Mooser, Robert Sladek, MAGIC investigators, GLGC Consortium, Kiran Musunuru, Albert V Smith, Andrew C Edmondson, Ioannis M Stylianou, Masahiro Koseki, James P Pirruccello, Daniel I Chasman, Christopher T Johansen, Sigrid W Fouchier, Gina M Peloso, Maja Barbalic, Sally L Ricketts, Joshua C Bis, Mary F Feitosa, Marju Orho-Melander, Olle Melander, Xiaohui Li, Mingyao Li, Yoon Shin Cho, Min Jin Go, Young Jin Kim, Jong-Young Lee, Taesung Park, Kyunga Kim, Xueling Sim, Rick Twee-Hee Ong, Damien C Croteau-Chonka, Leslie A Lange, Joshua D Smith, Andreas Ziegler, Weihua Zhang, Robert Y L Zee, John B Whitfield, John R Thompson, Ida Surakka, Tim D Spector, Johannes H Smit, Juha Sinisalo, James Scott, Juha Saharinen, Chiara Sabatti, Lynda M Rose, Robert Roberts, Mark Rieder, Alex N Parker, Guillaume Pare, Christopher J O'Donnell, Markku S Nieminen, Deborah A Nickerson, Grant W Montgomery, Wendy McArdle, David Masson, Nicholas G Martin, Fabio Marroni, Gavin Lucas, Robert Luben, Marja-Liisa Lokki, Guillaume Lettre, Lenore J Launer, Edward G Lakatta, Reijo Laaksonen, Kirsten O Kyvik, Inke R König, Kay-Tee Khaw, Lee M Kaplan, Åsa Johansson, A Cecile J W Janssens, Wilmar Igl, G Kees Hovingh, Christian Hengstenberg, Aki S Havulinna, Nicholas D Hastie, Tamara B Harris, Talin Haritunians, Alistair S Hall, Leif C Groop, Elena Gonzalez, Nelson B Freimer, Jeanette Erdmann, Kenechi G Ejebe, Angela Döring, Anna F Dominiczak, Serkalem Demissie, Panagiotis Deloukas, Ulf de Faire, Gabriel Crawford, Yii-der I Chen, Mark J Caulfield, S Matthijs Boekholdt, Themistocles L Assimes, Thomas Quertermous, Mark Seielstad, Tien Y Wong, E-Shyong Tai, Alan B Feranil, Christopher W Kuzawa, Herman A Taylor, Stacey B Gabriel, Hilma Holm, Vilmundur Gudnason, Ronald M Krauss, Jose M Ordovas, Patricia B Munroe, Jaspal S Kooner, Alan R Tall, Robert A Hegele, John J P Kastelein, Eric E Schadt, David P Strachan, Muredach P Reilly, Nilesh J Samani, Heribert Schunkert, L Adrienne Cupples, Manjinder S Sandhu, Paul M Ridker, Daniel J Rader, and Sekar Kathiresan

Subjects
Genetics, QH426-470
Abstract

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p

Published
2012
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5. Correction: Identification, Replication, and Fine-Mapping of Loci Associated with Adult Height in Individuals of African Ancestry.

Author

Amidou N'Diaye, Gary K. Chen, Cameron D. Palmer, Bing Ge, Bamidele Tayo, Rasika A. Mathias, Jingzhong Ding, Michael A. Nalls, Adebowale Adeyemo, Véronique Adoue, Christine B. Ambrosone, Larry Atwood, Elisa V. Bandera, Lewis C. Becker, Sonja I. Berndt, Leslie Bernstein, William J. Blot, Eric Boerwinkle, Angela Britton, Graham Casey, Stephen J. Chanock, Ellen Demerath, Sandra L. Deming, W. Ryan Diver, Caroline Fox, Tamara B. Harris, Dena G. Hernandez, Jennifer J. Hu, Sue A. Ingles, Esther M. John, Craig Johnson, Brendan Keating, Rick A. Kittles, Laurence N. Kolonel, Stephen B. Kritchevsky, Loic Le Marchand, Kurt Lohman, Jiankang Liu, Robert C. Millikan, Adam Murphy, Solomon Musani, Christine Neslund-Dudas, Kari E. North, Sarah Nyante, Adesola Ogunniyi, Elaine A. Ostrander, George Papanicolaou, Sanjay Patel, Curtis A. Pettaway, Michael F. Press, Susan Redline, Jorge L. Rodriguez-Gil, Charles Rotimi, Benjamin A. Rybicki, Babatunde Salako, Pamela J. Schreiner, Lisa B. Signorello, Andrew B. Singleton, Janet L. Stanford, Alex H. Stram, Daniel O. Stram, Sara S. Strom, Bhoom Suktitipat, Michael J. Thun, John S. Witte, Lisa R. Yanek, Regina G. Ziegler, Wei Zheng, Xiaofeng Zhu, Joseph M. Zmuda, Alan B. Zonderman, Michele K. Evans, Yongmei Liu, Diane M. Becker, Richard S. Cooper, Tomi Pastinen, Brian E. Henderson, Joel N. Hirschhorn, Guillaume Lettre, and Christopher A. Haiman

Subjects
Genetics, QH426-470
Published
2011
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6. Identification, replication, and fine-mapping of Loci associated with adult height in individuals of african ancestry.

Author

Amidou N'Diaye, Gary K Chen, Cameron D Palmer, Bing Ge, Bamidele Tayo, Rasika A Mathias, Jingzhong Ding, Michael A Nalls, Adebowale Adeyemo, Véronique Adoue, Christine B Ambrosone, Larry Atwood, Elisa V Bandera, Lewis C Becker, Sonja I Berndt, Leslie Bernstein, William J Blot, Eric Boerwinkle, Angela Britton, Graham Casey, Stephen J Chanock, Ellen Demerath, Sandra L Deming, W Ryan Diver, Caroline Fox, Tamara B Harris, Dena G Hernandez, Jennifer J Hu, Sue A Ingles, Esther M John, Craig Johnson, Brendan Keating, Rick A Kittles, Laurence N Kolonel, Stephen B Kritchevsky, Loic Le Marchand, Kurt Lohman, Jiankang Liu, Robert C Millikan, Adam Murphy, Solomon Musani, Christine Neslund-Dudas, Kari E North, Sarah Nyante, Adesola Ogunniyi, Elaine A Ostrander, George Papanicolaou, Sanjay Patel, Curtis A Pettaway, Michael F Press, Susan Redline, Jorge L Rodriguez-Gil, Charles Rotimi, Benjamin A Rybicki, Babatunde Salako, Pamela J Schreiner, Lisa B Signorello, Andrew B Singleton, Janet L Stanford, Alex H Stram, Daniel O Stram, Sara S Strom, Bhoom Suktitipat, Michael J Thun, John S Witte, Lisa R Yanek, Regina G Ziegler, Wei Zheng, Xiaofeng Zhu, Joseph M Zmuda, Alan B Zonderman, Michele K Evans, Yongmei Liu, Diane M Becker, Richard S Cooper, Tomi Pastinen, Brian E Henderson, Joel N Hirschhorn, Guillaume Lettre, and Christopher A Haiman

Subjects
Genetics, QH426-470
Abstract

Adult height is a classic polygenic trait of high heritability (h(2) approximately 0.8). More than 180 single nucleotide polymorphisms (SNPs), identified mostly in populations of European descent, are associated with height. These variants convey modest effects and explain approximately10% of the variance in height. Discovery efforts in other populations, while limited, have revealed loci for height not previously implicated in individuals of European ancestry. Here, we performed a meta-analysis of genome-wide association (GWA) results for adult height in 20,427 individuals of African ancestry with replication in up to 16,436 African Americans. We found two novel height loci (Xp22-rs12393627, P = 3.4×10(-12) and 2p14-rs4315565, P = 1.2×10(-8)). As a group, height associations discovered in European-ancestry samples replicate in individuals of African ancestry (P = 1.7×10(-4) for overall replication). Fine-mapping of the European height loci in African-ancestry individuals showed an enrichment of SNPs that are associated with expression of nearby genes when compared to the index European height SNPs (P

Published
2011
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7. Genome-wide association study of white blood cell count in 16,388 African Americans: the continental origins and genetic epidemiology network (COGENT).

Author

Alexander P Reiner, Guillaume Lettre, Michael A Nalls, Santhi K Ganesh, Rasika Mathias, Melissa A Austin, Eric Dean, Sampath Arepalli, Angela Britton, Zhao Chen, David Couper, J David Curb, Charles B Eaton, Myriam Fornage, Struan F A Grant, Tamara B Harris, Dena Hernandez, Naoyuki Kamatini, Brendan J Keating, Michiaki Kubo, Andrea LaCroix, Leslie A Lange, Simin Liu, Kurt Lohman, Yan Meng, Emile R Mohler, Solomon Musani, Yusuke Nakamura, Christopher J O'Donnell, Yukinori Okada, Cameron D Palmer, George J Papanicolaou, Kushang V Patel, Andrew B Singleton, Atsushi Takahashi, Hua Tang, Herman A Taylor, Kent Taylor, Cynthia Thomson, Lisa R Yanek, Lingyao Yang, Elad Ziv, Alan B Zonderman, Aaron R Folsom, Michele K Evans, Yongmei Liu, Diane M Becker, Beverly M Snively, and James G Wilson

Subjects
Genetics, QH426-470
Abstract

Total white blood cell (WBC) and neutrophil counts are lower among individuals of African descent due to the common African-derived "null" variant of the Duffy Antigen Receptor for Chemokines (DARC) gene. Additional common genetic polymorphisms were recently associated with total WBC and WBC sub-type levels in European and Japanese populations. No additional loci that account for WBC variability have been identified in African Americans. In order to address this, we performed a large genome-wide association study (GWAS) of total WBC and cell subtype counts in 16,388 African-American participants from 7 population-based cohorts available in the Continental Origins and Genetic Epidemiology Network. In addition to the DARC locus on chromosome 1q23, we identified two other regions (chromosomes 4q13 and 16q22) associated with WBC in African Americans (P

Published
2011
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8. 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
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9. Genome-wide association study of asthma in individuals of African ancestry reveals novel asthma susceptibility loci

Author

Michelle Daya, Nicholas Rafaels, Sameer Chavan, Henry Richard Johnston, Aniket Shetty, Christopher R. Gignoux, Meher Preethi Boorgula, Monica Campbell, Pissamai Maul, Trevor Maul, Candelaria Vergara, Albert M. Levin, Genevieve Wojcik, Dara G. Torgerson, Victor E. Ortega, Ayo Doumatey, Maria Ilma Araujo, Pedro C. Avila, Eugene Bleecker, Carlos Bustamante, Luis Caraballo, Georgia M. Dunston, Mezbah U. Faruque, Trevor S. Ferguson, Camila Figueiredo, Jean G. Ford, Pierre-Antoine Gourraud, Nadia N. Hansel, Ryan D. Hernandez, Edwin Francisco Herrera-Paz, Eimear E. Kenny, Jennifer Knight-Madden, Rajesh Kumar, Lesli A. Lange, Ethan M. Lange, Antoine Lizee, Alvaro Mayorga, Deborah Meyers, Dan L. Nicolae, Timothy D. O’Connor, Ricardo Riccio Oliveira, Christopher O. Olopade, Olufunmilayo Olopade, Zhaohui S. Qin, Charles Rotimi, Harold Watson, Rainford J. Wilks, L. Keoki Williams, James G. Wilson, Carole Ober, Esteban G. Burchard, Terri H. Beaty, Margaret A. Taub, Ingo Ruczinski, Rasika Ann Mathias, Kathleen C. Barnes, Ayola Akim Adegnika, Ganiyu Arinola, Ulysse Ateba-Ngoa, Gerardo Ayestas, Adolfo Correa, Francisco M. De La Vega, Celeste Eng, Said Omar Leiva Erazo, Marilyn G. Foreman, Cassandra Foster, Li Gao, Jingjing Gao, Kimberly Gietzen, Leslie Grammer, Linda Gutierrez, Mark Hansen, Tina Hartert, Yijuan Hu, Kwang-Youn A. Kim, Pamela Landaverde-Torres, Javier Marrugo, Beatriz Martinez, Rosella Martinez, Luis F. Mayorga, Delmy-Aracely Mejia-Mejia, Catherine Meza, Solomon Musani, Shaila Musharoff, Oluwafemi Oluwole, Maria Pino-Yanes, Hector Ramos, Allan Saenz, Steven Salzberg, Maureen Samms-Vaughan, Robert Schleimer, Alan F. Scott, Suyash S. Shringarpure, Wei Song, Zachary A. Szpiech, Raul Torres, Gloria Varela, Olga Marina Vasquez, Lorraine B. Ware, and Maria Yazdanbakhsh

Subjects
Genetics, Genotype, medicine, Chromosome, SNP, Genetic admixture, Single-nucleotide polymorphism, Genome-wide association study, Allele, Biology, medicine.disease, Asthma
Abstract

BACKGROUNDAsthma is a complex disease with striking disparities across racial and ethnic groups, which may be partly attributable to genetic factors. One of the main goals of the Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) is to discover genes conferring risk to asthma in populations of African descent.METHODSWe performed a genome-wide meta-analysis of asthma across 11 CAAPA datasets (4,827 asthma cases and 5,397 controls), genotyped on the African Diaspora Power Chip (ADPC) and including existing GWAS array data. The genotype data were imputed up to a whole genome sequence reference panel from n=880 African ancestry individuals for a total of 61,904,576 SNPs. Statistical models appropriate to each study design were used to test for association, and results were combined using the weighted Z-score method. We also used admixture mapping as a complementary approach to identify loci involved in asthma pathogenesis in subjects of African ancestry.RESULTSSNPs rs787160 and rs17834780 on chromosome 2q22.3 were significantly associated with asthma (p=6.57 × 10−9 and 2.97 × 10−8, respectively). These SNPs lie in the intergenic region between the Rho GTPase Activating Protein 15 (ARHGAP15) and Glycosyltransferase Like Domain Containing 1 (GTDC1) genes. Four low frequency variants on chromosome 1q21.3, which may be involved in the “atopic march” and which are not polymorphic in Europeans, also showed evidence for association with asthma (1.18 ×10−6 ≤ p ≤ 3.06 ×10−6). SNP rs11264909 on chromosome 1q23.1, close to a region previously identified by the EVE asthma meta-analysis as having a putative African ancestry specific effect, only showed differences in counts in subjects homozygous for alleles of African ancestry. Admixture mapping also identified a significantly associated region on chromosome 6q23.2, which includes the Transcription Factor 21 (TCF21) gene, previously shown to be differentially expressed in bronchial tissues of asthmatics and non-asthmatics.CONCLUSIONSWe have identified a number of novel asthma association signals warranting further investigation.

Published
2017
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10. Abstract MP35: Relation of Left Ventricular Structure to Incident Heart Failure in African Americans: The Jackson Cohort of the Atherosclerosis Risk in Communities Study

Author

Amir Azeem, Walter L Beard, Solomon Musani, Kenneth R Butler, Thomas H Mosley, and Ervin R Fox

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

Introduction: Studies in non-Hispanic whites suggest that early adaptive changes in cardiac structure due to hypertension may influence the development of heart failure (HF). The predictive value of left ventricular (LV) structure to incident acute decompensated HF (ADHF) has not been well-studied in African Americans (AA) despite the higher incidence of HF in this group. Hypothesis: We hypothesized that incidence of ADHF in AA varies according to cardiac structures and LV geometry type. Methods: The study sample included 1,737 participants who attended the third examination cycle of the Jackson cohort of ARIC between 1993 and1995 and underwent echocardiography, anthropometry and phlebotomy for glucose and lipids. Left atrial size, aortic root diameter (AOD), LV wall thicknesses and chamber dimensions, LV mass, LV mass index, LV hypertrophy (LVH) and LV geometric patterns [normal geometry, concentric hypertrophy, eccentric hypertrophy (EH), concentric remodeling] were determined by echocardiography. Cutoff for LVH was defined as above the 80th percentile of LV mass index. HF data was available up to December 31, 2011. In the primary analyses we adjusted for age, sex, smoking, diabetes, body mass index, systolic blood pressure, and use of hypertension medications in the multivariable model. Results: Over a follow-up period of approximately 18 years, 188 participants developed ADHF. Incident ADHF was significantly related to AOD [HR 1.42 (1.03, 1.97)], LV internal diameter in diastole (cm) [HR 1.60 (1.24, 2.05)], LV mass [HR 1.003 (1.002, 1.005)], LVM index [HR 1.01 (1.004, 1.02) and LVH [HR 1.62 (1.16, 2.27)]. In terms of LV geometry, EH was significantly related to incident ADHF in the multivariable model [HR 2.94 (1.70-5.10)]. Conclusion: In our large community-based sample of AAs, we observed that AOD, LV internal diameter in diastole, LV mass, LV mass index, LVH and EH geometry were significantly related to long-term incidence of ADHF independent of standard risk factors. These findings suggest echocardiography may be helpful in risk stratifying members of this high risk population for ADHF.

Published
2016
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12. Abstract P099: The Relation of Kidney Disease to Measures of Digital Arterial Tonometry in the Jackson Heart Study

Author

Eric McClendon, Solomon Musani, Sushante Khaire, Herman Taylor, and Ervin Fox

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

Background: The presence of chronic kidney disease is greater in African Americans than in non-Hispanic whites. Though there is data to show a relation between endothelial dysfunction and end-stage kidney disease, the relation to mild and moderate chronic kidney disease (particularly in African Americans) is unclear. Methods and Results: Digital arterial tonometry was performed during Exam 2 and 3 of the Jackson Heart Study using the endoPAT2000. Data from digital arterial tonometry included baseline pulse wave amplitude (BPA) as a measure of endothelial tone and reactive hyperemic index (F-RHI) as a measure of endothelial function. For this study, the estimated glomerular filtration rate (eGFR) was calculated using the MDRD equation. Those participants with eGFR < 60 ml/min/1.73m2 were defined as having CKD. Participants with eGFR < 15 ml/min/1.73m2 were excluded from the analysis. Microalbuminuria in this study was defined as a urinary albumin:creatinine ratio ≥ 17mg/g in men and ≥ 25 mg/g in women. We compared the differences in least square means adjusted for age and sex, and adjusted for multiple traditional clinical covariates using a generalized linear model. Results: There were 834 participants in the study population (mean age 58.5 years, 61% women); 87 (10.4%) participants with CKD and 108 (13.0%) with microalbuminuria. In age and sex adjusted samples, we found that both BPA and F-RHI were significantly associated with CKD in the pooled samples. However in multivariable adjusted analysis the relation was no longer significant in either the pooled or sex-specific samples. In the multivariable adusted analysis,BPA was significantly (P=0.036) associated with microalbuminuria in men and F-RHI was weakly significantly (P=0.08) associated with microalbuminuria in women. Conclusion: We found that endothelial dysfunction as measured by digital arterial tonometry is not significantly associated with chronic kidney disease. There is an association of endothelial tone in men and endothelial dysfunction in women with microalbuminuria.

Published
2012
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13. Population genetic structure of Anopheles arabiensis (Diptera: Culicidae) in a rice growing area of central Kenya

Author

Ephantus J, Muturi, Chang-Hyun, Kim, Frederick N, Baliraine, Solomon, Musani, Benjamin, Jacob, John, Githure, and Robert J, Novak

Subjects
Anopheles, Animals, Genetic Variation, Agriculture, Oryza, Kenya, Article, Demography
Abstract

Studies were conducted to examine the population genetic structure of Anopheles arabiensis (Patton) in Mwea Rice Irrigation Scheme and surrounding areas in Central Kenya, under different agricultural systems. This study was motivated by observed differences in malaria transmission indices of An. arabiensis within the scheme compared with adjacent nonirrigated areas. Agricultural practices can modify local microclimate and influence the number and diversity of larval habitats and in so doing may occasion subpopulation differentiation. Thirty samples from each of the three study sites were genotyped at eight microsatellite loci. Seven microsatellite loci showed high polymorphism but revealed no genetic differentiation (FST = 0.006, P = 0.312) and high gene flow (Nm = 29–101) among the three populations. Genetic bottleneck analysis showed no indication of excess heterozygosity in any of the populations. There was high frequency of rare alleles, suggesting that An. arabiensis in the study area has a high potential of responding to selective pressures from environmental changes and vector control efforts. These findings imply that An. arabiensis in the study area occurs as a single, continuous panmictic population with great ability to adapt to human-imposed selective pressures.

Published
2010

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