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3. Predicting chronic postsurgical pain: current evidence and a novel program to develop predictive biomarker signatures

Author

Sluka, Kathleen A, Wager, Tor D, Sutherland, Stephani P, Labosky, Patricia A, Balach, Tessa, Bayman, Emine O, Berardi, Giovanni, Brummett, Chad M, Burns, John, Buvanendran, Asokumar, Caffo, Brian, Calhoun, Vince D, Clauw, Daniel, Chang, Andrew, Coffey, Christopher S, Dailey, Dana L, Ecklund, Dixie, Fiehn, Oliver, Fisch, Kathleen M, Law, Laura A Frey, Harris, Richard E, Harte, Steven E, Howard, Timothy D, Jacobs, Joshua, Jacobs, Jon M, Jepsen, Kristen, Johnston, Nicolas, Langefeld, Carl D, Laurent, Louise C, Lenzi, Rebecca, Lindquist, Martin A, Lokshin, Anna, Kahn, Ari, McCarthy, Robert J, Olivier, Michael, Porter, Linda, Qian, Wei-Jun, Sankar, Cheryse A, Satterlee, John, Swensen, Adam C, Vance, Carol GT, Waljee, Jennifer, Wandner, Laura D, Williams, David A, Wixson, Richard L, Zhou, Xiaohong Joe, and Consortium, the A2CPS

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Precision Medicine, Pain Research, Biotechnology, Clinical Research, Behavioral and Social Science, Chronic Pain, Prevention, 4.1 Discovery and preclinical testing of markers and technologies, 2.1 Biological and endogenous factors, Good Health and Well Being, Humans, Proteomics, Pain, Postoperative, Acute Pain, Biomarkers, Pain, Chronic pain, Postsurgical pain, Biomarker, Biosignatures, Omics, Brain imaging, Psychosocial, A2CPS Consortium, Medical and Health Sciences, Psychology and Cognitive Sciences, Anesthesiology, Biomedical and clinical sciences, Health sciences, Psychology
Abstract

AbstractChronic pain affects more than 50 million Americans. Treatments remain inadequate, in large part, because the pathophysiological mechanisms underlying the development of chronic pain remain poorly understood. Pain biomarkers could potentially identify and measure biological pathways and phenotypical expressions that are altered by pain, provide insight into biological treatment targets, and help identify at-risk patients who might benefit from early intervention. Biomarkers are used to diagnose, track, and treat other diseases, but no validated clinical biomarkers exist yet for chronic pain. To address this problem, the National Institutes of Health Common Fund launched the Acute to Chronic Pain Signatures (A2CPS) program to evaluate candidate biomarkers, develop them into biosignatures, and discover novel biomarkers for chronification of pain after surgery. This article discusses candidate biomarkers identified by A2CPS for evaluation, including genomic, proteomic, metabolomic, lipidomic, neuroimaging, psychophysical, psychological, and behavioral measures. Acute to Chronic Pain Signatures will provide the most comprehensive investigation of biomarkers for the transition to chronic postsurgical pain undertaken to date. Data and analytic resources generatedby A2CPS will be shared with the scientific community in hopes that other investigators will extract valuable insights beyond A2CPS's initial findings. This article will review the identified biomarkers and rationale for including them, the current state of the science on biomarkers of the transition from acute to chronic pain, gaps in the literature, and how A2CPS will address these gaps.

Published
2023

4. Molecular pathways identified from single nucleotide polymorphisms demonstrate mechanistic differences in systemic lupus erythematosus patients of Asian and European ancestry.

Author

Owen, Katherine A, Bell, Kristy A, Price, Andrew, Bachali, Prathyusha, Ainsworth, Hannah, Marion, Miranda C, Howard, Timothy D, Langefeld, Carl D, Shen, Nan, Yazdany, Jinoos, Dall'era, Maria, Grammer, Amrie C, and Lipsky, Peter E

Subjects
Humans, Lupus Erythematosus, Systemic, Genetic Predisposition to Disease, Case-Control Studies, Genotype, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Lupus, Clinical Research, Autoimmune Disease, Human Genome, Genetics, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system
Abstract

Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disorder with a prominent genetic component. Individuals of Asian-Ancestry (AsA) disproportionately experience more severe SLE compared to individuals of European-Ancestry (EA), including increased renal involvement and tissue damage. However, the mechanisms underlying elevated severity in the AsA population remain unclear. Here, we utilized available gene expression data and genotype data based on all non-HLA SNP associations in EA and AsA SLE patients detected using the Immunochip genotyping array. We identified 2778 ancestry-specific and 327 trans-ancestry SLE-risk polymorphisms. Genetic associations were examined using connectivity mapping and gene signatures based on predicted biological pathways and were used to interrogate gene expression datasets. SLE-associated pathways in AsA patients included elevated oxidative stress, altered metabolism and mitochondrial dysfunction, whereas SLE-associated pathways in EA patients included a robust interferon response (type I and II) related to enhanced cytosolic nucleic acid sensing and signaling. An independent dataset derived from summary genome-wide association data in an AsA cohort was interrogated and identified similar molecular pathways. Finally, gene expression data from AsA SLE patients corroborated the molecular pathways predicted by SNP associations. Identifying ancestry-related molecular pathways predicted by genetic SLE risk may help to disentangle the population differences in clinical severity that impact AsA and EA individuals with SLE.

Published
2023

5. Multi-Site Observational Study to Assess Biomarkers for Susceptibility or Resilience to Chronic Pain: The Acute to Chronic Pain Signatures (A2CPS) Study Protocol

Author

Berardi, Giovanni, Frey-Law, Laura, Sluka, Kathleen A, Bayman, Emine O, Coffey, Christopher S, Ecklund, Dixie, Vance, Carol GT, Dailey, Dana L, Burns, John, Buvanendran, Asokumar, McCarthy, Robert J, Jacobs, Joshua, Zhou, Xiaohong Joe, Wixson, Richard, Balach, Tessa, Brummett, Chad M, Clauw, Daniel, Colquhoun, Douglas, Harte, Steven E, Harris, Richard E, Williams, David A, Chang, Andrew C, Waljee, Jennifer, Fisch, Kathleen M, Jepsen, Kristen, Laurent, Louise C, Olivier, Michael, Langefeld, Carl D, Howard, Timothy D, Fiehn, Oliver, Jacobs, Jon M, Dakup, Panshak, Qian, Wei-Jun, Swensen, Adam C, Lokshin, Anna, Lindquist, Martin, Caffo, Brian S, Crainiceanu, Ciprian, Zeger, Scott, Kahn, Ari, Wager, Tor, Taub, Margaret, Ford, James, Sutherland, Stephani P, and Wandner, Laura D

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Pain Research, Prevention, Chronic Pain, Clinical Research, Neurological, Musculoskeletal, Good Health and Well Being, postsurgical pain, thoracic surgery, pain, biomarker, risk factors, protocol, knee arthroplasty, Biomedical and clinical sciences, Health sciences
Abstract

Chronic pain has become a global health problem contributing to years lived with disability and reduced quality of life. Advances in the clinical management of chronic pain have been limited due to incomplete understanding of the multiple risk factors and molecular mechanisms that contribute to the development of chronic pain. The Acute to Chronic Pain Signatures (A2CPS) Program aims to characterize the predictive nature of biomarkers (brain imaging, high-throughput molecular screening techniques, or "omics," quantitative sensory testing, patient-reported outcome assessments and functional assessments) to identify individuals who will develop chronic pain following surgical intervention. The A2CPS is a multisite observational study investigating biomarkers and collective biosignatures (a combination of several individual biomarkers) that predict susceptibility or resilience to the development of chronic pain following knee arthroplasty and thoracic surgery. This manuscript provides an overview of data collection methods and procedures designed to standardize data collection across multiple clinical sites and institutions. Pain-related biomarkers are evaluated before surgery and up to 3 months after surgery for use as predictors of patient reported outcomes 6 months after surgery. The dataset from this prospective observational study will be available for researchers internal and external to the A2CPS Consortium to advance understanding of the transition from acute to chronic postsurgical pain.

Published
2022

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

Author

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

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

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

Published
2021

7. Integrative Analysis of Glucometabolic Traits, Adipose Tissue DNA Methylation and Gene Expression Identifies Epigenetic Regulatory Mechanisms of Insulin Resistance and Obesity in African Americans

Author

Sharma, Neeraj K, Comeau, Mary E, Montoya, Dennis, Pellegrini, Matteo, Howard, Timothy D, Langefeld, Carl D, and Das, Swapan K

Subjects
Biomedical and Clinical Sciences, Obesity, Diabetes, Nutrition, Genetics, Biotechnology, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Adipose Tissue, Adult, Black or African American, Computational Biology, DNA Methylation, Epigenesis, Genetic, Female, Gene Expression Regulation, Glucose, Humans, Insulin Resistance, Male, Transcriptome, Medical and Health Sciences, Endocrinology & Metabolism, Biomedical and clinical sciences
Abstract

Decline in insulin sensitivity due to dysfunction of adipose tissue (AT) is one of the earliest pathogenic events in type 2 diabetes. We hypothesize that differential DNA methylation (DNAm) controls insulin sensitivity and obesity by modulating transcript expression in AT. Integrating AT DNAm profiles with transcript profile data measured in a cohort of 230 African Americans (AAs) from the African American Genetics of Metabolism and Expression cohort, we performed cis-expression quantitative trait methylation (cis-eQTM) analysis to identify epigenetic regulatory loci for glucometabolic trait-associated transcripts. We identified significantly associated cytosine-guanine dinucleotide regions for 82 transcripts (false discovery rate [FDR]-P < 0.05). The strongest eQTM locus was observed for the proopiomelanocortin (POMC; ρ = -0.632, P = 4.70 × 10-27) gene. Epigenome-wide association studies (EWAS) further identified 155, 46, and 168 cytosine-guanine dinucleotide regions associated (FDR-P < 0.05) with the Matsuda index, SI, and BMI, respectively. Intersection of EWAS, transcript level to trait association, and eQTM results, followed by causal inference test identified significant eQTM loci for 23 genes that were also associated with Matsuda index, SI, and/or BMI in EWAS. These associated genes include FERMT3, ITGAM, ITGAX, and POMC In summary, applying an integrative multiomics approach, our study provides evidence for DNAm-mediated regulation of gene expression at both previously identified and novel loci for many key AT transcripts influencing insulin resistance and obesity.

Published
2020

9. Transancestral mapping and genetic load in systemic lupus erythematosus.

Author

Langefeld, Carl D, Ainsworth, Hannah C, Cunninghame Graham, Deborah S, Kelly, Jennifer A, Comeau, Mary E, Marion, Miranda C, Howard, Timothy D, Ramos, Paula S, Croker, Jennifer A, Morris, David L, Sandling, Johanna K, Almlöf, Jonas Carlsson, Acevedo-Vásquez, Eduardo M, Alarcón, Graciela S, Babini, Alejandra M, Baca, Vicente, Bengtsson, Anders A, Berbotto, Guillermo A, Bijl, Marc, Brown, Elizabeth E, Brunner, Hermine I, Cardiel, Mario H, Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M, Dahlqvist, Solbritt Rantapää, D'Alfonso, Sandra, Da Silva, Berta Martins, de la Rúa Figueroa, Iñigo, Doria, Andrea, Edberg, Jeffrey C, Endreffy, Emőke, Esquivel-Valerio, Jorge A, Fortin, Paul R, Freedman, Barry I, Frostegård, Johan, García, Mercedes A, de la Torre, Ignacio García, Gilkeson, Gary S, Gladman, Dafna D, Gunnarsson, Iva, Guthridge, Joel M, Huggins, Jennifer L, James, Judith A, Kallenberg, Cees GM, Kamen, Diane L, Karp, David R, Kaufman, Kenneth M, Kottyan, Leah C, Kovács, László, Laustrup, Helle, Lauwerys, Bernard R, Li, Quan-Zhen, Maradiaga-Ceceña, Marco A, Martín, Javier, McCune, Joseph M, McWilliams, David R, Merrill, Joan T, Miranda, Pedro, Moctezuma, José F, Nath, Swapan K, Niewold, Timothy B, Orozco, Lorena, Ortego-Centeno, Norberto, Petri, Michelle, Pineau, Christian A, Pons-Estel, Bernardo A, Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D, Russell, Laurie P, Sabio, José M, Aguilar-Salinas, Carlos A, Scherbarth, Hugo R, Scorza, Raffaella, Seldin, Michael F, Sjöwall, Christopher, Svenungsson, Elisabet, Thompson, Susan D, Toloza, Sergio MA, Truedsson, Lennart, Tusié-Luna, Teresa, Vasconcelos, Carlos, Vilá, Luis M, Wallace, Daniel J, Weisman, Michael H, Wither, Joan E, Bhangale, Tushar, Oksenberg, Jorge R, Rioux, John D, Gregersen, Peter K, Syvänen, Ann-Christine, Rönnblom, Lars, Criswell, Lindsey A, Jacob, Chaim O, Sivils, Kathy L, Tsao, Betty P, Schanberg, Laura E, and Behrens, Timothy W

Subjects
Humans, Lupus Erythematosus, Systemic, HLA Antigens, Logistic Models, Case-Control Studies, Mutagenesis, Insertional, Age of Onset, Sequence Deletion, Genetic Load, Multifactorial Inheritance, Polymorphism, Single Nucleotide, African Continental Ancestry Group, American Native Continental Ancestry Group, European Continental Ancestry Group, Hispanic Americans, Lupus Erythematosus, Systemic, Mutagenesis, Insertional, Polymorphism, Single Nucleotide
Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (∼50% of these regions have multiple independent associations); these include 24 novel SLE regions (P

Published
2017

11. Analysis of Trans-Ancestral SLE Risk Loci Identifies Unique Biologic Networks and Drug Targets in African and European Ancestries

Author

Owen, Katherine A., Price, Andrew, Ainsworth, Hannah, Aidukaitis, Bryce N., Bachali, Prathyusha, Catalina, Michelle D., Dittman, James M., Howard, Timothy D., Kingsmore, Kathryn M., Labonte, Adam C., Marion, Miranda C., Robl, Robert D., Zimmerman, Kip D., Langefeld, Carl D., Grammer, Amrie C., and Lipsky, Peter E.

Published
2020
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13. Genome-wide association study identifies TH1 pathway genes associated with lung function in asthmatic patients

Author

Li, Xingnan, Hawkins, Gregory A, Ampleford, Elizabeth J, Moore, Wendy C, Li, Huashi, Hastie, Annette T, Howard, Timothy D, Boushey, Homer A, Busse, William W, Calhoun, William J, Castro, Mario, Erzurum, Serpil C, Israel, Elliot, Lemanske, Robert F, Szefler, Stanley J, Wasserman, Stephen I, Wenzel, Sally E, Peters, Stephen P, Meyers, Deborah A, and Bleecker, Eugene R

Subjects
Biomedical and Clinical Sciences, Immunology, Asthma, Human Genome, Lung, Clinical Research, Genetics, Aetiology, 2.1 Biological and endogenous factors, Respiratory, Female, Forced Expiratory Volume, Genome-Wide Association Study, Humans, Interferon Regulatory Factor-2, Interleukin-12, Male, Polymorphism, Single Nucleotide, Respiratory Function Tests, STAT4 Transcription Factor, Th1 Cells, Vital Capacity, Lung function, FEV1, asthma, T(H)1, IL12A, IL12RB1, STAT4, IRF2, ACRN, ATS, American Thoracic Society, Asthma Clinical Research Network, BASALT, Best Adjustment Strategy for Asthma in Long Term, CSGA, Collaborative Studies on the Genetics of Asthma, FEV(1), FVC, Forced vital capacity, GWAS, Genome-wide association study, LD, Linkage disequilibrium, NHLBI, National Heart, Lung, and Blood Institute, Percent predicted FEV(1), Percent predicted forced vital capacity, SARP, SNP, Severe Asthma Research Program, Single nucleotide polymorphism, TALC, TENOR, The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens, Tiotropium Bromide as an Alternative to Increased Inhaled Corticosteroid in Patients Inadequately Controlled on a Lower Dose of Inhaled Corticosteroids, ppFEV(1), ppFVC, Allergy
Abstract

BackgroundRecent meta-analyses of genome-wide association studies in general populations of European descent have identified 28 loci for lung function.ObjectiveWe sought to identify novel lung function loci specifically for asthma and to confirm lung function loci identified in general populations.MethodsGenome-wide association studies of lung function (percent predicted FEV1 [ppFEV1], percent predicted forced vital capacity, and FEV1/forced vital capacity ratio) were performed in 4 white populations of European descent (n = 1544), followed by meta-analyses.ResultsSeven of 28 previously identified lung function loci (HHIP, FAM13A, THSD4, GSTCD, NOTCH4-AGER, RARB, and ZNF323) identified in general populations were confirmed at single nucleotide polymorphism (SNP) levels (P < .05). Four of 32 loci (IL12A, IL12RB1, STAT4, and IRF2) associated with ppFEV1 (P < 10(-4)) belong to the TH1 or IL-12 cytokine family pathway. By using a linear additive model, these 4 TH1 pathway SNPs cumulatively explained 2.9% to 7.8% of the variance in ppFEV1 values in 4 populations (P = 3 × 10(-11)). Genetic scores of these 4 SNPs were associated with ppFEV1 values (P = 2 × 10(-7)) and the American Thoracic Society severe asthma classification (P = .005) in the Severe Asthma Research Program population. TH2 pathway genes (IL13, TSLP, IL33, and IL1RL1) conferring asthma susceptibility were not associated with lung function.ConclusionGenes involved in airway structure/remodeling are associated with lung function in both general populations and asthmatic subjects. TH1 pathway genes involved in anti-virus/bacterial infection and inflammation modify lung function in asthmatic subjects. Genes associated with lung function that might affect asthma severity are distinct from those genes associated with asthma susceptibility.

Published
2013

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

Author

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

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

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

Published
2013

24. Supplementary Figure 3 from Effects of Pubertal Exposure to Dietary Soy on Estrogen Receptor Activity in the Breast of Cynomolgus Macaques

Author

Dewi, Fitriya N., primary, Wood, Charles E., primary, Willson, Cynthia J., primary, Register, Thomas C., primary, Lees, Cynthia J., primary, Howard, Timothy D., primary, Huang, Zhiqing, primary, Murphy, Susan K., primary, Tooze, Janet A., primary, Chou, Jeff W., primary, Miller, Lance D., primary, and Cline, J. Mark, primary

Published
2023
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25. Data from Effects of Pubertal Exposure to Dietary Soy on Estrogen Receptor Activity in the Breast of Cynomolgus Macaques

Author

Dewi, Fitriya N., primary, Wood, Charles E., primary, Willson, Cynthia J., primary, Register, Thomas C., primary, Lees, Cynthia J., primary, Howard, Timothy D., primary, Huang, Zhiqing, primary, Murphy, Susan K., primary, Tooze, Janet A., primary, Chou, Jeff W., primary, Miller, Lance D., primary, and Cline, J. Mark, primary

Published
2023
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26. Supplementary Figure 1 from Effects of Pubertal Exposure to Dietary Soy on Estrogen Receptor Activity in the Breast of Cynomolgus Macaques

Author

Dewi, Fitriya N., primary, Wood, Charles E., primary, Willson, Cynthia J., primary, Register, Thomas C., primary, Lees, Cynthia J., primary, Howard, Timothy D., primary, Huang, Zhiqing, primary, Murphy, Susan K., primary, Tooze, Janet A., primary, Chou, Jeff W., primary, Miller, Lance D., primary, and Cline, J. Mark, primary

Published
2023
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27. Supplementary Table 1 from Effects of Pubertal Exposure to Dietary Soy on Estrogen Receptor Activity in the Breast of Cynomolgus Macaques

Author

Dewi, Fitriya N., primary, Wood, Charles E., primary, Willson, Cynthia J., primary, Register, Thomas C., primary, Lees, Cynthia J., primary, Howard, Timothy D., primary, Huang, Zhiqing, primary, Murphy, Susan K., primary, Tooze, Janet A., primary, Chou, Jeff W., primary, Miller, Lance D., primary, and Cline, J. Mark, primary

Published
2023
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28. Supplementary Table 2 from Effects of Pubertal Exposure to Dietary Soy on Estrogen Receptor Activity in the Breast of Cynomolgus Macaques

Author

Dewi, Fitriya N., primary, Wood, Charles E., primary, Willson, Cynthia J., primary, Register, Thomas C., primary, Lees, Cynthia J., primary, Howard, Timothy D., primary, Huang, Zhiqing, primary, Murphy, Susan K., primary, Tooze, Janet A., primary, Chou, Jeff W., primary, Miller, Lance D., primary, and Cline, J. Mark, primary

Published
2023
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29. Supplementary Figure 2 from Effects of Pubertal Exposure to Dietary Soy on Estrogen Receptor Activity in the Breast of Cynomolgus Macaques

Author

Dewi, Fitriya N., primary, Wood, Charles E., primary, Willson, Cynthia J., primary, Register, Thomas C., primary, Lees, Cynthia J., primary, Howard, Timothy D., primary, Huang, Zhiqing, primary, Murphy, Susan K., primary, Tooze, Janet A., primary, Chou, Jeff W., primary, Miller, Lance D., primary, and Cline, J. Mark, primary

Published
2023
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30. Supplementary Table 3 from Effects of Pubertal Exposure to Dietary Soy on Estrogen Receptor Activity in the Breast of Cynomolgus Macaques

Author

Dewi, Fitriya N., primary, Wood, Charles E., primary, Willson, Cynthia J., primary, Register, Thomas C., primary, Lees, Cynthia J., primary, Howard, Timothy D., primary, Huang, Zhiqing, primary, Murphy, Susan K., primary, Tooze, Janet A., primary, Chou, Jeff W., primary, Miller, Lance D., primary, and Cline, J. Mark, primary

Published
2023
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34. The modifying influence of HLA class II DQB1∗06:02 on the Streptococcus and clinical phenotype correlation among anti-Ro+ mothers of children with neonatal lupus

Author

Clancy, Robert M., primary, Guthridge, Carla J., additional, Marion, Miranda C., additional, Guthridge, Joel, additional, Howard, Timothy D., additional, Izmirly, Peter M., additional, Masson, Mala, additional, Buyon, Jill P., additional, James, Judith A., additional, and Langefeld, Carl D., additional

Published
2022
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36. Meta-analysis of Genome-wide Association Studies Identifies 1q22 as a Susceptibility Locus for Intracerebral Hemorrhage

Author

Woo, Daniel, Falcone, Guido J., Devan, William J., Brown, W. Mark, Biffi, Alessandro, Howard, Timothy D., Anderson, Christopher D., Brouwers, H. Bart, Valant, Valerie, Battey, Thomas W.K., Radmanesh, Farid, Raffeld, Miriam R., Baedorf-Kassis, Sylvia, Deka, Ranjan, Woo, Jessica G., Martin, Lisa J., Haverbusch, Mary, Moomaw, Charles J., Sun, Guangyun, Broderick, Joseph P., Flaherty, Matthew L., Martini, Sharyl R., Kleindorfer, Dawn O., Kissela, Brett, Comeau, Mary E., Jagiella, Jeremiasz M., Schmidt, Helena, Freudenberger, Paul, Pichler, Alexander, Enzinger, Christian, Hansen, Björn M., Norrving, Bo, Jimenez-Conde, Jordi, Giralt-Steinhauer, Eva, Elosua, Roberto, Cuadrado-Godia, Elisa, Soriano, Carolina, Roquer, Jaume, Kraft, Peter, Ayres, Alison M., Schwab, Kristin, McCauley, Jacob L., Pera, Joanna, Urbanik, Andrzej, Rost, Natalia S., Goldstein, Joshua N., Viswanathan, Anand, Stögerer, Eva-Maria, Tirschwell, David L., Selim, Magdy, Brown, Devin L., Silliman, Scott L., Worrall, Bradford B., Meschia, James F., Kidwell, Chelsea S., Montaner, Joan, Fernandez-Cadenas, Israel, Delgado, Pilar, Malik, Rainer, Dichgans, Martin, Greenberg, Steven M., Rothwell, Peter M., Lindgren, Arne, Slowik, Agnieszka, Schmidt, Reinhold, Langefeld, Carl D., and Rosand, Jonathan

Published
2014
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37. Proteomic Architecture of Human Coronary and Aortic Atherosclerosis

Author

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

Published
2018
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40. Genome‐Wide Association Meta‐Analysis Reveals Novel Juvenile Idiopathic Arthritis Susceptibility Loci

Author

McIntosh, Laura A., Marion, Miranda C., Sudman, Marc, Comeau, Mary E., Becker, Mara L., Bohnsack, John F., Fingerlin, Tasha E., Griffin, Thomas A., Haas, J. Peter, Lovell, Daniel J., Maier, Lisa A., Nigrovic, Peter A., Prahalad, Sampath, Punaro, Marilynn, Rosé, Carlos D., Wallace, Carol A., Wise, Carol A., Moncrieffe, Halima, Howard, Timothy D., Langefeld, Carl D., and Thompson, Susan D.

Published
2017
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42. Genome-wide ancestry association testing identifies a common European variant on 6q14.1 as a risk factor for asthma in African American subjects

Author

Torgerson, Dara G., Capurso, Daniel, Ampleford, Elizabeth J., Li, Xingnan, Moore, Wendy C., Gignoux, Christopher R., Hu, Donglei, Eng, Celeste, Mathias, Rasika A., Busse, William W., Castro, Mario, Erzurum, Serpil C., Fitzpatrick, Anne M., Gaston, Benjamin, Israel, Elliot, Jarjour, Nizar N., Teague, W. Gerald, Wenzel, Sally E., Rodríguez-Santana, José R., Rodríguez-Cintrón, William, Avila, Pedro C., Ford, Jean G., Barnes, Kathleen C., Burchard, Esteban G., Howard, Timothy D., Bleecker, Eugene R., Meyers, Deborah A., Cox, Nancy J., Ober, Carole, and Nicolae, Dan L.

Published
2012
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45. Social Factors, Epigenomics and Lupus in African American Women (SELA) Study: protocol for an observational mechanistic study examining the interplay of multiple individual and social factors on lupus outcomes in a health disparity population

Author

Vara, Emily L, primary, Langefeld, Carl D, additional, Wolf, Bethany J, additional, Howard, Timothy D, additional, Hawkins, Gregory A, additional, Quet, Queen, additional, Moultrie, Lee H, additional, Quinnette King, L, additional, Molano, Ivan D, additional, Bray, Stephanie L, additional, Ueberroth, Lori Ann, additional, Lim, S Sam, additional, Williams, Edith M, additional, Kamen, Diane L, additional, and Ramos, Paula S, additional

Published
2022
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47. Importance of hedgehog interacting protein and other lung function genes in asthma

Author

Li, Xingnan, Howard, Timothy D., Moore, Wendy C., Ampleford, Elizabeth J., Li, Huashi, Busse, William W., Calhoun, William J., Castro, Mario, Chung, Kian Fan, Erzurum, Serpil C., Fitzpatrick, Anne M., Gaston, Benjamin, Israel, Elliot, Jarjour, Nizar N., Teague, W. Gerald, Wenzel, Sally E., Peters, Stephen P., Hawkins, Gregory A., Bleecker, Eugene R., and Meyers, Deborah A.

Published
2011
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49. Multi-Site Observational Study to Assess Biomarkers for Susceptibility or Resilience to Chronic Pain: The Acute to Chronic Pain Signatures (A2CPS) Study Protocol

Author

Berardi, Giovanni, primary, Frey-Law, Laura, additional, Sluka, Kathleen A., additional, Bayman, Emine O., additional, Coffey, Christopher S., additional, Ecklund, Dixie, additional, Vance, Carol G. T., additional, Dailey, Dana L., additional, Burns, John, additional, Buvanendran, Asokumar, additional, McCarthy, Robert J., additional, Jacobs, Joshua, additional, Zhou, Xiaohong Joe, additional, Wixson, Richard, additional, Balach, Tessa, additional, Brummett, Chad M., additional, Clauw, Daniel, additional, Colquhoun, Douglas, additional, Harte, Steven E., additional, Harris, Richard E., additional, Williams, David A., additional, Chang, Andrew C., additional, Waljee, Jennifer, additional, Fisch, Kathleen M., additional, Jepsen, Kristen, additional, Laurent, Louise C., additional, Olivier, Michael, additional, Langefeld, Carl D., additional, Howard, Timothy D., additional, Fiehn, Oliver, additional, Jacobs, Jon M., additional, Dakup, Panshak, additional, Qian, Wei-Jun, additional, Swensen, Adam C., additional, Lokshin, Anna, additional, Lindquist, Martin, additional, Caffo, Brian S., additional, Crainiceanu, Ciprian, additional, Zeger, Scott, additional, Kahn, Ari, additional, Wager, Tor, additional, Taub, Margaret, additional, Ford, James, additional, Sutherland, Stephani P., additional, and Wandner, Laura D., additional

Published
2022
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50. The Social Factors, Epigenomics, and Lupus in African American Women (SELA) study: protocol for an observational mechanistic study examining the interplay of multiple individual and social factors on lupus outcomes in a health disparity population

Author

Vara, Emily L., primary, Langefeld, Carl D., additional, Wolf, Bethany J., additional, Howard, Timothy D., additional, Hawkins, Gregory A., additional, Quet, Queen, additional, Moultrie, Lee H., additional, King, L. Quinnette, additional, Molano, Ivan D., additional, Bray, Stephanie L., additional, Ueberroth, Lori Ann, additional, Lim, S. Sam, additional, Williams, Edith M., additional, Kamen, Diane L., additional, and Ramos, Paula S., additional

Published
2022
Full Text
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