Search

Your search keyword '"Levin, Albert M."' showing total 558 results
Start Over Author "Levin, Albert M."
558 results on '"Levin, Albert M."'

2. Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed

Author

Taub, Margaret A, Conomos, Matthew P, Keener, Rebecca, Iyer, Kruthika R, Weinstock, Joshua S, Yanek, Lisa R, Lane, John, Miller-Fleming, Tyne W, Brody, Jennifer A, Raffield, Laura M, McHugh, Caitlin P, Jain, Deepti, Gogarten, Stephanie M, Laurie, Cecelia A, Keramati, Ali, Arvanitis, Marios, Smith, Albert V, Heavner, Benjamin, Barwick, Lucas, Becker, Lewis C, Bis, Joshua C, Blangero, John, Bleecker, Eugene R, Burchard, Esteban G, Celedón, Juan C, Chang, Yen Pei C, Custer, Brian, Darbar, Dawood, de las Fuentes, Lisa, DeMeo, Dawn L, Freedman, Barry I, Garrett, Melanie E, Gladwin, Mark T, Heckbert, Susan R, Hidalgo, Bertha A, Irvin, Marguerite R, Islam, Talat, Johnson, W Craig, Kaab, Stefan, Launer, Lenore, Lee, Jiwon, Liu, Simin, Moscati, Arden, North, Kari E, Peyser, Patricia A, Rafaels, Nicholas, Seidman, Christine, Weeks, Daniel E, Wen, Fayun, Wheeler, Marsha M, Williams, L Keoki, Yang, Ivana V, Zhao, Wei, Aslibekyan, Stella, Auer, Paul L, Bowden, Donald W, Cade, Brian E, Chen, Zhanghua, Cho, Michael H, Cupples, L Adrienne, Curran, Joanne E, Daya, Michelle, Deka, Ranjan, Eng, Celeste, Fingerlin, Tasha E, Guo, Xiuqing, Hou, Lifang, Hwang, Shih-Jen, Johnsen, Jill M, Kenny, Eimear E, Levin, Albert M, Liu, Chunyu, Minster, Ryan L, Naseri, Take, Nouraie, Mehdi, Reupena, Muagututi A Sefuiva, Sabino, Ester C, Smith, Jennifer A, Smith, Nicholas L, Lasky-Su, Jessica, Taylor, James G, Telen, Marilyn J, Tiwari, Hemant K, Tracy, Russell P, White, Marquitta J, Zhang, Yingze, Wiggins, Kerri L, Weiss, Scott T, Vasan, Ramachandran S, Taylor, Kent D, Sinner, Moritz F, Silverman, Edwin K, Shoemaker, M Benjamin, Sheu, Wayne H-H, Sciurba, Frank, Schwartz, David A, Rotter, Jerome I, Roden, Daniel, Redline, Susan, and Raby, Benjamin A

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Human Genome, Biotechnology, Aetiology, 2.1 Biological and endogenous factors, Generic health relevance, Good Health and Well Being, NHLBI CARE Network, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed Hematology and Hemostasis Working Group, TOPMed Structural Variation Working Group
Abstract

Genetic studies on telomere length are important for understanding age-related diseases. Prior GWAS for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally-diverse individuals (European, African, Asian and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n=109,122 individuals. We identified 59 sentinel variants (p-value

Published
2022

3. Multiple Correspondence Analysis and HLA-Associations of Organ Involvement in a Large Cohort of African-American and European-American Patients with Sarcoidosis

Author

Rasmussen, Astrid, Dawkins, Bryan A., Li, Chuang, Pezant, Nathan, Levin, Albert M., Rybicki, Benjamin A., and Iannuzzi, Michael C.

Subjects
Mortality -- Analysis, HLA histocompatibility antigens -- Analysis, Histocompatibility antigens -- Analysis, African Americans -- Analysis, Health
Abstract

Sarcoidosis is a systemic granulomatous disease with predominant pulmonary involvement and vast heterogeneity of clinical manifestations and disease outcomes. African American (AA) patients suffer greater morbidity and mortality. Using Multiple Correspondence Analysis, we identified seven clusters of organ involvement in European American (EA; n = 385) patients which were similar to those previously described in a Pan-European (GenPhenReSa) and a Spanish cohort (SARCOGEAS). In contrast, AA (n = 987) had six, less well-defined and overlapping clusters with little similarity to the cluster identified in the EA cohort evaluated at the same U.S. institutions. Association of cluster membership with two-digit HLA-DRB1 alleles demonstrated ancestry-specific patterns of association and replicated known HLA effects. These results further support the notion that genetically influenced immune risk profiles, which differ based on ancestry, play a role in phenotypic heterogeneity. Dissecting such risk profiles will move us closer to personalized medicine for this complex disease., Author(s): Astrid Rasmussen [sup.1], Bryan A. Dawkins [sup.1], Chuang Li [sup.1], Nathan Pezant [sup.1], Albert M. Levin [sup.2], Benjamin A. Rybicki [sup.2], Michael C. Iannuzzi [sup.3], Courtney G. Montgomery [sup.1] [...]

Published
2023
Full Text
View/download PDF

6. Mapping the 17q12-21.1 Locus for Variants Associated with Early-Onset Asthma in African Americans.

Author

Gui, Hongsheng, Levin, Albert M, Hu, Donglei, Sleiman, Patrick, Xiao, Shujie, Mak, Angel CY, Yang, Mao, Barczak, Andrea J, Huntsman, Scott, Eng, Celeste, Hochstadt, Samantha, Zhang, Ellen, Whitehouse, Kyle, Simons, Samantha, Cabral, Whitney, Takriti, Sami, Abecasis, Gonçalo, Blackwell, Thomas W, Kang, Hyun Min, Nickerson, Deborah A, Germer, Soren, Lanfear, David E, Gilliland, Frank, Gauderman, W James, Kumar, Rajesh, Erle, David J, Martinez, Fernando D, Hakonarson, Hakon, Burchard, Esteban G, and Williams, L Keoki

Subjects
Lung, Asthma, Genetics, Aetiology, 2.1 Biological and endogenous factors, Respiratory, Adolescent, Adult, Black or African American, Age of Onset, Child, Child, Preschool, Chromosome Mapping, Chromosomes, Human, Pair 17, Female, Genetic Association Studies, Genetic Predisposition to Disease, Genetic Variation, Humans, Infant, Infant, Newborn, Linkage Disequilibrium, Male, Middle Aged, Polymorphism, Single Nucleotide, Quantitative Trait Loci, United States, White People, Young Adult, asthma, African Americans, chromosome 17, GSDMB, ORMDL3, Medical and Health Sciences, Respiratory System
Abstract

Rationale: The 17q12-21.1 locus is one of the most highly replicated genetic associations with asthma. Individuals of African descent have lower linkage disequilibrium in this region, which could facilitate identifying causal variants.Objectives: To identify functional variants at 17q12-21.1 associated with early-onset asthma among African American individuals.Methods: We evaluated African American participants from SAPPHIRE (Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-Ethnicity) (n = 1,940), SAGE II (Study of African Americans, Asthma, Genes and Environment) (n = 885), and GCPD-A (Study of the Genetic Causes of Complex Pediatric Disorders-Asthma) (n = 2,805). Associations with asthma onset at ages under 5 years were meta-analyzed across cohorts. The lead signal was reevaluated considering haplotypes informed by genetic ancestry (i.e., African vs. European). Both an expression-quantitative trait locus analysis and a phenome-wide association study were performed on the lead variant.Measurements and Main Results: The meta-analyzed results from SAPPHIRE, SAGE II, and the GCPD-A identified rs11078928 as the top association for early-onset asthma. A haplotype analysis suggested that the asthma association partitioned most closely with the rs11078928 genotype. Genetic ancestry did not appear to influence the effect of this variant. In the expression-quantitative trait locus analysis, rs11078928 was related to alternative splicing of GSDMB (gasdermin-B) transcripts. The phenome-wide association study of rs11078928 suggested that this variant was predominantly associated with asthma and asthma-associated symptoms.Conclusions: A splice-acceptor polymorphism appears to be a causal variant for asthma at the 17q12-21.1 locus. This variant appears to have the same magnitude of effect in individuals of African and European descent.

Published
2021

9. Asthma and its relationship to mitochondrial copy number: Results from the Asthma Translational Genomics Collaborative (ATGC) of the Trans-Omics for Precision Medicine (TOPMed) program.

Author

Cocco, Maxwell P, White, Evan, Xiao, Shujie, Hu, Donglei, Mak, Angel, Sleiman, Patrick, Yang, Mao, Bobbitt, Kevin R, Gui, Hongsheng, Levin, Albert M, Hochstadt, Samantha, Whitehouse, Kyle, Rynkowski, Dean, Barczak, Andrea J, Abecasis, Gonçalo, Blackwell, Thomas W, Kang, Hyun Min, Nickerson, Deborah A, Germer, Soren, Ding, Jun, Lanfear, David E, Gilliland, Frank, Gauderman, W James, Kumar, Rajesh, Erle, David J, Martinez, Fernando, Hakonarson, Hakon, Burchard, Esteban G, and Williams, L Keoki

Subjects
Leukocytes, Humans, Asthma, Electron Transport Chain Complex Proteins, DNA, Mitochondrial, RNA, Flow Cytometry, Logistic Models, Proportional Hazards Models, Sensitivity and Specificity, Cohort Studies, Base Sequence, Adult, Middle Aged, African Americans, Female, Male, Young Adult, DNA Copy Number Variations, Translational Medical Research, Whole Genome Sequencing, Human Genome, Biotechnology, Lung, Clinical Research, Genetics, Respiratory, General Science & Technology
Abstract

BackgroundMitochondria support critical cellular functions, such as energy production through oxidative phosphorylation, regulation of reactive oxygen species, apoptosis, and calcium homeostasis.ObjectiveGiven the heightened level of cellular activity in patients with asthma, we sought to determine whether mitochondrial DNA (mtDNA) copy number measured in peripheral blood differed between individuals with and without asthma.MethodsWhole genome sequence data was generated as part of the Trans-Omics for Precision Medicine (TOPMed) Program on participants from the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE) and the Study of African Americans, Asthma, Genes, & Environment II (SAGE II). We restricted our analysis to individuals who self-identified as African American (3,651 asthma cases and 1,344 controls). Mitochondrial copy number was estimated using the sequencing read depth ratio for the mitochondrial and nuclear genomes. Respiratory complex expression was assessed using RNA-sequencing.ResultsAverage mitochondrial copy number was significantly higher among individuals with asthma when compared with controls (SAPPHIRE: 218.60 vs. 200.47, P

Published
2020

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

Author

Kachroo, Priyadarshini, Hecker, Julian, Chawes, Bo L, Ahluwalia, Tarunveer S, Cho, Michael H, Qiao, Dandi, Kelly, Rachel S, Chu, Su H, Virkud, Yamini V, Huang, Mengna, Barnes, Kathleen C, Burchard, Esteban G, Eng, Celeste, Hu, Donglei, Celedón, Juan C, Daya, Michelle, Levin, Albert M, Gui, Hongsheng, Williams, L Keoki, Forno, Erick, Mak, Angel CY, Avila, Lydiana, Soto-Quiros, Manuel E, Cloutier, Michelle M, Acosta-Pérez, Edna, Canino, Glorisa, Bønnelykke, Klaus, Bisgaard, Hans, Raby, Benjamin A, Lange, Christoph, Weiss, Scott T, Lasky-Su, Jessica A, National Heart, Lung, Abe, Namiko, Abecasis, Goncalo, Albert, Christine, Allred, Nicholette Palmer, Almasy, Laura, Alonso, Alvaro, Ament, Seth, Anderson, Peter, Anugu, Pramod, Applebaum-Bowden, Deborah, Arking, Dan, Arnett, Donna K, Ashley-Koch, Allison, Aslibekyan, Stella, Assimes, Tim, Auer, Paul, Avramopoulos, Dimitrios, Barnard, John, Barnes, Kathleen, Barr, R Graham, Barron-Casella, Emily, Beaty, Terri, Becker, Diane, Becker, Lewis, Beer, Rebecca, Begum, Ferdouse, Beitelshees, Amber, Benjamin, Emelia, Bezerra, Marcos, Bielak, Larry, Bis, Joshua, Blackwell, Thomas, Blangero, John, Boerwinkle, Eric, Borecki, Ingrid, Bowler, Russell, Brody, Jennifer, Broeckel, Ulrich, Broome, Jai, Bunting, Karen, Burchard, Esteban, Cardwell, Jonathan, Carty, Cara, Casaburi, Richard, Casella, James, Chaffin, Mark, Chang, Christy, Chasman, Daniel, Chavan, Sameer, Chen, Bo-Juen, Chen, Wei-Min, Chen, Yii-Der Ida, Choi, Seung Hoan, Chuang, Lee-Ming, Chung, Mina, Cornell, Elaine, Correa, Adolfo, Crandall, Carolyn, Crapo, James, Cupples, L Adrienne, Curran, Joanne, Curtis, Jeffrey, Custer, Brian, Damcott, Coleen, Darbar, Dawood, and Das, Sayantan

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

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

Published
2019

11. Author Correction: Association study in African-admixed populations across the Americas recapitulates asthma risk loci in non-African populations.

Author

Daya, Michelle, Rafaels, Nicholas, Brunetti, Tonya M, Chavan, Sameer, Levin, Albert M, Shetty, Aniket, Gignoux, Christopher R, Boorgula, Meher Preethi, Wojcik, Genevieve, Campbell, Monica, Vergara, Candelaria, Torgerson, Dara G, Ortega, Victor E, Doumatey, Ayo, Johnston, Henry Richard, Acevedo, Nathalie, Araujo, Maria Ilma, Avila, Pedro C, Belbin, Gillian, Bleecker, Eugene, Bustamante, Carlos, Caraballo, Luis, Cruz, Alvaro, Dunston, Georgia M, Eng, Celeste, Faruque, Mezbah U, Ferguson, Trevor S, Figueiredo, Camila, Ford, Jean G, Gan, Weiniu, Gourraud, Pierre-Antoine, Hansel, Nadia N, Hernandez, Ryan D, Herrera-Paz, Edwin Francisco, Jiménez, Silvia, Kenny, Eimear E, Knight-Madden, Jennifer, Kumar, Rajesh, Lange, Leslie A, Lange, Ethan M, Lizee, Antoine, Maul, Pissamai, Maul, Trevor, Mayorga, Alvaro, Meyers, Deborah, Nicolae, Dan L, O'Connor, Timothy D, Oliveira, Ricardo Riccio, Olopade, Christopher O, Olopade, Olufunmilayo, Qin, Zhaohui S, Rotimi, Charles, Vince, Nicolas, Watson, Harold, Wilks, Rainford J, Wilson, James G, Salzberg, Steven, Ober, Carole, Burchard, Esteban G, Williams, L Keoki, Beaty, Terri H, Taub, Margaret A, Ruczinski, Ingo, Mathias, Rasika A, Barnes, Kathleen C, and CAAPA

Subjects
CAAPA
Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2019

12. A genome-wide association and admixture mapping study of bronchodilator drug response in African Americans with asthma

Author

Spear, Melissa L, Hu, Donglei, Pino-Yanes, Maria, Huntsman, Scott, Eng, Celeste, Levin, Albert M, Ortega, Victor E, White, Marquitta J, McGarry, Meghan E, Thakur, Neeta, Galanter, Joshua, Mak, Angel CY, Oh, Sam S, Ampleford, Elizabeth, Peters, Stephen P, Davis, Adam, Kumar, Rajesh, Farber, Harold J, Meade, Kelley, Avila, Pedro C, Serebrisky, Denise, Lenoir, Michael A, Brigino-Buenaventura, Emerita, Cintron, William Rodriguez, Thyne, Shannon M, Rodriguez-Santana, Jose R, Ford, Jean G, Chapela, Rocio, Estrada, Andrés Moreno, Sandoval, Karla, Seibold, Max A, Winkler, Cheryl A, Bleecker, Eugene R, Myers, Deborah A, Williams, L Keoki, Hernandez, Ryan D, Torgerson, Dara G, and Burchard, Esteban G

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Lung, Genetics, Asthma, Human Genome, Respiratory, Pharmacology & Pharmacy, Pharmacology and pharmaceutical sciences
Abstract

Short-acting β2-adrenergic receptor agonists (SABAs) are the most commonly prescribed asthma medications worldwide. Response to SABAs is measured as bronchodilator drug response (BDR), which varies among racial/ethnic groups in the United States. However, the genetic variation that contributes to BDR is largely undefined in African Americans with asthma. To identify genetic variants that may contribute to differences in BDR in African Americans with asthma, we performed a genome-wide association study (GWAS) of BDR in 949 African-American children with asthma, genotyped with the Axiom World Array 4 (Affymetrix, Santa Clara, CA) followed by imputation using 1000 Genomes phase III genotypes. We used linear regression models adjusting for age, sex, body mass index (BMI) and genetic ancestry to test for an association between BDR and genotype at single-nucleotide polymorphisms (SNPs). To increase power and distinguish between shared vs. population-specific associations with BDR in children with asthma, we performed a meta-analysis across 949 African Americans and 1830 Latinos (total = 2779). Finally, we performed genome-wide admixture mapping to identify regions whereby local African or European ancestry is associated with BDR in African Americans. We identified a population-specific association with an intergenic SNP on chromosome 9q21 that was significantly associated with BDR (rs73650726, p = 7.69 × 10-9). A trans-ethnic meta-analysis across African Americans and Latinos identified three additional SNPs within the intron of PRKG1 that were significantly associated with BDR (rs7903366, rs7070958 and rs7081864, p ≤ 5 × 10-8). Our results failed to replicate in three additional populations of 416 Latinos and 1615 African Americans. Our findings indicate that both population-specific and shared genetic variation contributes to differences in BDR in minority children with asthma, and that the genetic underpinnings of BDR may differ between racial/ethnic groups.

Published
2019

13. Integrative approach identifies corticosteroid response variant in diverse populations with asthma

Author

Levin, Albert M, Gui, Hongsheng, Hernandez-Pacheco, Natalia, Yang, Mao, Xiao, Shujie, Yang, James J, Hochstadt, Samantha, Barczak, Andrea J, Eckalbar, Walter L, Rynkowski, Dean, Samedy, Lesly-Anne, Kwok, Pui-Yan, Pino-Yanes, Maria, Erle, David J, Lanfear, David E, Burchard, Esteban G, and Williams, L Keoki

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Lung, Genetics, Patient Safety, Human Genome, Clinical Trials and Supportive Activities, Clinical Research, Asthma, Respiratory, Adolescent, Adrenal Cortex Hormones, Adult, Black or African American, Child, Cohort Studies, Disease Progression, Eosinophil-Derived Neurotoxin, Eosinophils, Genome-Wide Association Study, Genotype, Hispanic or Latino, Humans, Leukocyte Count, Male, Metered Dose Inhalers, Middle Aged, Pharmacogenomic Variants, Phenotype, Polymorphism, Single Nucleotide, Treatment Outcome, United States, Young Adult, Pharmacogenetics, EDDM3B, RNASE2, eosinophil-derived neurotoxin, transcriptome, eosinophils, Immunology, Allergy
Abstract

BackgroundAlthough inhaled corticosteroid (ICS) medication is considered the cornerstone treatment for patients with persistent asthma, few ICS pharmacogenomic studies have involved nonwhite populations.ObjectiveWe sought to identify genetic predictors of ICS response in multiple population groups with asthma.MethodsThe discovery group comprised African American participants from the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-Ethnicity (SAPPHIRE) who underwent 6 weeks of monitored ICS therapy (n = 244). A genome-wide scan was performed to identify single nucleotide polymorphism (SNP) variants jointly associated (ie, the combined effect of the SNP and SNP × ICS treatment interaction) with changes in asthma control. Top associations were validated by assessing the joint association with asthma exacerbations in 3 additional groups: African Americans (n = 803 and n = 563) and Latinos (n = 1461). RNA sequencing data from 408 asthmatic patients and 405 control subjects were used to examine whether genotype was associated with gene expression.ResultsOne variant, rs3827907, was significantly associated with ICS-mediated changes in asthma control in the discovery set (P = 7.79 × 10-8) and was jointly associated with asthma exacerbations in 3 validation cohorts (P = .023, P = .029, and P = .041). RNA sequencing analysis found the rs3827907 C-allele to be associated with lower RNASE2 expression (P = 6.10 × 10-4). RNASE2 encodes eosinophil-derived neurotoxin, and the rs3827907 C-allele appeared to particularly influence ICS treatment response in the presence of eosinophilic inflammation (ie, high pretreatment eosinophil-derived neurotoxin levels or blood eosinophil counts).ConclusionWe identified a variant, rs3827907, that appears to influence response to ICS treatment in multiple population groups and likely mediates its effect through eosinophils.

Published
2019

14. An admixture mapping meta-analysis implicates genetic variation at 18q21 with asthma susceptibility in Latinos

Author

Gignoux, Christopher R, Torgerson, Dara G, Pino-Yanes, Maria, Uricchio, Lawrence H, Galanter, Joshua, Roth, Lindsey A, Eng, Celeste, Hu, Donglei, Nguyen, Elizabeth A, Huntsman, Scott, Mathias, Rasika A, Kumar, Rajesh, Rodriguez-Santana, Jose, Thakur, Neeta, Oh, Sam S, McGarry, Meghan, Moreno-Estrada, Andres, Sandoval, Karla, Winkler, Cheryl A, Seibold, Max A, Padhukasahasram, Badri, Conti, David V, Farber, Harold J, Avila, Pedro, Brigino-Buenaventura, Emerita, Lenoir, Michael, Meade, Kelley, Serebrisky, Denise, Borrell, Luisa N, Rodriguez-Cintron, William, Thyne, Shannon, Joubert, Bonnie R, Romieu, Isabelle, Levin, Albert M, Sienra-Monge, Juan-Jose, Del Rio-Navarro, Blanca Estela, Gan, Weiniu, Raby, Benjamin A, Weiss, Scott T, Bleecker, Eugene, Meyers, Deborah A, Martinez, Fernando J, Gauderman, W James, Gilliland, Frank, London, Stephanie J, Bustamante, Carlos D, Nicolae, Dan L, Ober, Carole, Sen, Saunak, Barnes, Kathleen, Williams, L Keoki, Hernandez, Ryan D, and Burchard, Esteban G

Subjects
Biomedical and Clinical Sciences, Immunology, Human Genome, Clinical Research, Lung, Asthma, Genetics, Aetiology, 2.1 Biological and endogenous factors, Respiratory, Chromosome Mapping, Chromosomes, Human, Pair 18, Genetic Predisposition to Disease, Hispanic or Latino, Humans, Polymorphism, Single Nucleotide, Smad2 Protein, asthma exacerbations, admixture mapping, meta-analysis, Latinos, SMAD2, gene expression, targeted sequencing, rare variation, Allergy
Abstract

BackgroundAsthma is a common but complex disease with racial/ethnic differences in prevalence, morbidity, and response to therapies.ObjectiveWe sought to perform an analysis of genetic ancestry to identify new loci that contribute to asthma susceptibility.MethodsWe leveraged the mixed ancestry of 3902 Latinos and performed an admixture mapping meta-analysis for asthma susceptibility. We replicated associations in an independent study of 3774 Latinos, performed targeted sequencing for fine mapping, and tested for disease correlations with gene expression in the whole blood of more than 500 subjects from 3 racial/ethnic groups.ResultsWe identified a genome-wide significant admixture mapping peak at 18q21 in Latinos (P = 6.8 × 10-6), where Native American ancestry was associated with increased risk of asthma (odds ratio [OR], 1.20; 95% CI, 1.07-1.34; P = .002) and European ancestry was associated with protection (OR, 0.86; 95% CI, 0.77-0.96; P = .008). Our findings were replicated in an independent childhood asthma study in Latinos (P = 5.3 × 10-3, combined P = 2.6 × 10-7). Fine mapping of 18q21 in 1978 Latinos identified a significant association with multiple variants 5' of SMAD family member 2 (SMAD2) in Mexicans, whereas a single rare variant in the same window was the top association in Puerto Ricans. Low versus high SMAD2 blood expression was correlated with case status (13.4% lower expression; OR, 3.93; 95% CI, 2.12-7.28; P

Published
2019

15. Association study in African-admixed populations across the Americas recapitulates asthma risk loci in non-African populations.

Author

Daya, Michelle, Rafaels, Nicholas, Brunetti, Tonya M, Chavan, Sameer, Levin, Albert M, Shetty, Aniket, Gignoux, Christopher R, Boorgula, Meher Preethi, Wojcik, Genevieve, Campbell, Monica, Vergara, Candelaria, Torgerson, Dara G, Ortega, Victor E, Doumatey, Ayo, Johnston, Henry Richard, Acevedo, Nathalie, Araujo, Maria Ilma, Avila, Pedro C, Belbin, Gillian, Bleecker, Eugene, Bustamante, Carlos, Caraballo, Luis, Cruz, Alvaro, Dunston, Georgia M, Eng, Celeste, Faruque, Mezbah U, Ferguson, Trevor S, Figueiredo, Camila, Ford, Jean G, Gan, Weiniu, Gourraud, Pierre-Antoine, Hansel, Nadia N, Hernandez, Ryan D, Herrera-Paz, Edwin Francisco, Jiménez, Silvia, Kenny, Eimear E, Knight-Madden, Jennifer, Kumar, Rajesh, Lange, Leslie A, Lange, Ethan M, Lizee, Antoine, Maul, Pissamai, Maul, Trevor, Mayorga, Alvaro, Meyers, Deborah, Nicolae, Dan L, O'Connor, Timothy D, Oliveira, Ricardo Riccio, Olopade, Christopher O, Olopade, Olufunmilayo, Qin, Zhaohui S, Rotimi, Charles, Vince, Nicolas, Watson, Harold, Wilks, Rainford J, Wilson, James G, Salzberg, Steven, Ober, Carole, Burchard, Esteban G, Williams, L Keoki, Beaty, Terri H, Taub, Margaret A, Ruczinski, Ingo, Mathias, Rasika A, Barnes, Kathleen C, and CAAPA

Subjects
CAAPA, Chromosomes, Human, Pair 8, Chromosomes, Human, Pair 12, Chromosomes, Human, Pair 17, Humans, Asthma, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, African Americans, Hispanic Americans, United States, Genome-Wide Association Study, Genetic Loci, Chromosomes, Human, Pair 12, Pair 17, Pair 8, Polymorphism, Single Nucleotide
Abstract

Asthma is a complex disease with striking disparities across racial and ethnic groups. Despite its relatively high burden, representation of individuals of African ancestry in asthma genome-wide association studies (GWAS) has been inadequate, and true associations in these underrepresented minority groups have been inconclusive. We report the results of a genome-wide meta-analysis from the Consortium on Asthma among African Ancestry Populations (CAAPA; 7009 asthma cases, 7645 controls). We find strong evidence for association at four previously reported asthma loci whose discovery was driven largely by non-African populations, including the chromosome 17q12-q21 locus and the chr12q13 region, a novel (and not previously replicated) asthma locus recently identified by the Trans-National Asthma Genetic Consortium (TAGC). An additional seven loci reported by TAGC show marginal evidence for association in CAAPA. We also identify two novel loci (8p23 and 8q24) that may be specific to asthma risk in African ancestry populations.

Published
2019

16. Expression quantitative trait locus fine mapping of the 17q12–21 asthma locus in African American children: a genetic association and gene expression study

Author

Achten, Niek, Ainsworth, John, Akkerman, Nonna, Anderson, Elizabeth, Anderson, Larry J., Andrews, Howard, Armagost, Elizabeth, Aubuchon, Mary Ann, Bach, Julia, Bacharier, Leonard, Barnes, Kathrine L., Barone, Charles, Bauer, Irma, Beamer, Paloma, Becker, Patrice, Bednarek, Alyssa, Bellemore, Stacey, Bendixsen, Casper G., Biagini Myers, Jocelyn M., Billheimer, Dean, Billstrand, Christine, Birg, Geraldine, Blocki, Shirley, Bloomberg, Gordon, Bobbitt, Kevin, Bochkov, Yury, Bourgeois, Karen, Boushey, Homer, Brockman-Schneider, Rebecca, Brunwasser, Steven M., Budrevich, Richard, Burkle, Jeffrey W., Busse, William, Calatroni, Agustin, Campbell, Janice, Carlson-Dakes, Kirsten, Cassidy-Bushrow, Andrea, Chappell, James D., Chasman, Deborah, Chipps, Teresa M., Chirkova, Tatiana, Cole, Deanna, Connolly, Alexandra, Cootauco, Michelle, Costello, Kaitlin, Couch, Philip, Coull, Brent, Craven, Mark, Crisafi, Gina, Cruikshank, William, Curtsinger, Kristi, Custovic, Adnan, Das, Suman R., DaSilva, Douglas, Datta, Soma, Davidson, Brent, De La Ossa, Lydia, DeVries, Mark, Di, Qian, Dixon, Samara, Donnerbauer, Erin, Dorst, Marian, Doyle, Susan, Dresen, Amy, Dupont, William D., Durrange, Janet, Erickson, Heidi, Evans, Michael D., Ezell, Jerel, Farnham, Leanna, Filardo-Collins, Roxanne, Finazzo, Salvatore, Flege, Zachary, Fleurat, Conner, Floerke, Heather, Floerke, Dorothy, Foss, Terry, Freie, Angela, Frome, Wayne, Fye, Samantha, Gagalis, Lisa, Gammell, Rebecca, Gangnon, Ronald E., Ge, James E., Gebretsadik, Tebeb, Gergen, Peter, Gern, James E., Gibson, Heike, Gjerasi, Edlira, Gold, Diane R., Gonzalez, Nicole, Goodman, Kayla, Gress, Lisa, Grindle, Kristine, Groeschen, Taylor, Hallmark, Brian, Halonen, Marilyn, Hart, Jaime, Hartert, Tina V., Havstad, Suzanne, Heinritz, Patrick, Hensley Alford, Sharon, Herbstman, Julie, Hernandez, Kellie, Hoepner, Lori, Jackson, Daniel J., Jadhao, Samadhan J., Jaffee, Katy, James, Peter, Jezioro, Jacqueline, Jimenez Pescador, Marcia, Johnson, Christine C., Johnson, Tara, Johnson, Camille, Jones, Amelia, Jones, Kyra, Jones, Paul, Jordan, Carolina, Joseph, Christine LM, Kattan, Meyer, Keidel, Kristina, Keifer, Matthew C., Kelley, Rick, Khurana Hershey, Gurgit K., Kim, Haejin, Kloog, Itai, Koepel, Tammy Kronenwetter, Koerkenmeier, Clint, Ladick, Laura, Lamm, Carin, Larkin, Emma, Lederman, Howard, Lee-Parritz, Aviva, Leimenstoll, Stephanie, Lemanske, Jr., Robert F., LeMasters, Grace K., Levin, Albert M., Levine, Jessica, Liu, Xinhua, Liu, Zhouwen, Lopez, Silvia, Lothrop, Nathan, Lovinsky-Desir, Stephanie, Lukacs, Nicholas, Lynch, Susan, Lynch, Christian, Mann, Erik, Martin, Jennifer, Martin, Lisa, Martinez, Fernando D., Matsui, Elizabeth, McCauley, Katherine, Mccollum, Megan, McCullough, Judith, McKennon, Chris G., Meece, Jennifer, Mendonca, Eneida, Mikus, Lance, Miller, Rachel L., Minton, Patricia, Mitchell, Herman, Moon, Vicki, Moore, Paul E., Morgan, Wayne, Morgan, Valerie, Morgan, David, Murrison, Liza, Nicholas, Charlotte, Nicolae, Daniel, Nunez, Adam, O'Connor, George, O'Toole, Sharon, Ober, Carole, Olson, Brent F., Ong, Irene, Osmundson, Sarah, Ownby, Dennis, Pappas, Tressa, Perera, Frederica, Perzanowski, Matthew, Peterson, Edward, Pierce, Marcela, Price-Johnson, Penny, Rajamanickam, Victoria, Ramirez, Judyth, Ray, Kimberly, Renneberg, Megan, Requia, Weeberb, Riley, Kylie, Rivera, Janelle, Rivers, Neisha, Roberg, Kathy, Rogers, Theresa, Rosas-Salazar, Christian, Russell, Pat, Ryan, Patrick H., Sadovsky, Yoel, Salazar, Lisa, Sampson, Hugh, Sandel, Megan, Schoettler, Nathan, Schwartz, Joel, Scott, Dena, Seroogy, Christine M., Sharp, Renee, Shilts, Meghan H., Sigelman, Steve, Singh, Anne Marie, Sitarik, Alexandra, Smartt, Ernestine, Sorkness, Ronald, Sorkness, Christine, Spangenberg, Amber, Sperling, Rhoda, Spies, David, Stern, Debra A., Stoffel, Brandy, Peebles, R. Stokes, Stouffer, Gina, Strauchman Boyer, Cathey, Suddeuth, Caitlin, Tachinardi, Umberto, Tang, Deliang, Tang, Zhengzheng, Tate, Jena, Taylor, William, Tensing, Krista, Tesson, Elizabeth, Thompson, Kathy, Thompson, Emma, Tisler, Christopher, Togias, Alkis, Turi, Kedir, Turner, Victoria, Tuzova, Marina, VanWormer, Jeffrey J., Visness, Cynthia M., Vrtis, Rose, Wahlman, Anthony, Wang, Lena, Wegienka, Ganesa, Wells, Karen, Wentworth-Sheilds, William, Wheatley, Lisa, Whitney, Nitsa, Williams, L. Keoki, Witter, Frank, Wolfe, Christopher, Wood, Robert A., Woodcroft, Kimberley, Woodward, Kim B., Wright, Anne L., Wright, Rosalind, Wu, Pingsheng, Yaeger, Melissa, Yaniv, Perri, Zanobetti, Antonella, Zhang, Shirley, Zook, Patricia, Zoratti, Edward M., McKennan, Chris G, Magnaye, Kevin M, Altman, Matthew C, Washington, Charles, 3rd, Stanhope, Catherine, Naughton, Katherine A, Rosasco, Mario G, Bacharier, Leonard B, Gold, Diane R, Hartert, Tina, Khurana Hershey, Gurjit K, Hogarth, D Kyle, Jackson, Daniel J, Johnson, Christine C, Lemanske, Robert F, Lynch, Susan V, Mendonca, Eneida A, Miller, Rachel L, Naureckas, Edward T, O'Connor, George T, Seroogy, Christine M, White, Steven R, Wood, Robert A, Wright, Anne L, Zoratti, Edward M, Martinez, Fernando D, Nicolae, Dan L, Levin, Albert M, and Gern, James E

Published
2020
Full Text
View/download PDF

17. Detecting and distinguishing indicators of risk for suicide using clinical records

Author

Ahmedani, Brian K., Cannella, Cara E., Yeh, Hsueh-Han, Westphal, Joslyn, Simon, Gregory E., Beck, Arne, Rossom, Rebecca C., Lynch, Frances L., Lu, Christine Y., Owen-Smith, Ashli A., Sala-Hamrick, Kelsey J., Frank, Cathrine, Akinyemi, Esther, Beebani, Ganj, Busuito, Christopher, Boggs, Jennifer M., Daida, Yihe G., Waring, Stephen, Gui, Hongsheng, and Levin, Albert M.

Published
2022
Full Text
View/download PDF

18. Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Author

Waage, Johannes, Standl, Marie, Curtin, John A, Jessen, Leon E, Thorsen, Jonathan, Tian, Chao, Schoettler, Nathan, The 23andMe Research Team, AAGC collaborators, Flores, Carlos, Abdellaoui, Abdel, Ahluwalia, Tarunveer S, Alves, Alexessander C, Amaral, Andre FS, Antó, Josep M, Arnold, Andreas, Barreto-Luis, Amalia, Baurecht, Hansjörg, van Beijsterveldt, Catharina EM, Bleecker, Eugene R, Bonàs-Guarch, Sílvia, Boomsma, Dorret I, Brix, Susanne, Bunyavanich, Supinda, Burchard, Esteban G, Chen, Zhanghua, Curjuric, Ivan, Custovic, Adnan, den Dekker, Herman T, Dharmage, Shyamali C, Dmitrieva, Julia, Duijts, Liesbeth, Ege, Markus J, Gauderman, W James, Georges, Michel, Gieger, Christian, Gilliland, Frank, Granell, Raquel, Gui, Hongsheng, Hansen, Torben, Heinrich, Joachim, Henderson, John, Hernandez-Pacheco, Natalia, Holt, Patrick, Imboden, Medea, Jaddoe, Vincent WV, Jarvelin, Marjo-Riitta, Jarvis, Deborah L, Jensen, Kamilla K, Jónsdóttir, Ingileif, Kabesch, Michael, Kaprio, Jaakko, Kumar, Ashish, Lee, Young-Ae, Levin, Albert M, Li, Xingnan, Lorenzo-Diaz, Fabian, Melén, Erik, Mercader, Josep M, Meyers, Deborah A, Myers, Rachel, Nicolae, Dan L, Nohr, Ellen A, Palviainen, Teemu, Paternoster, Lavinia, Pennell, Craig E, Pershagen, Göran, Pino-Yanes, Maria, Probst-Hensch, Nicole M, Rüschendorf, Franz, Simpson, Angela, Stefansson, Kari, Sunyer, Jordi, Sveinbjornsson, Gardar, Thiering, Elisabeth, Thompson, Philip J, Torrent, Maties, Torrents, David, Tung, Joyce Y, Wang, Carol A, Weidinger, Stephan, Weiss, Scott, Willemsen, Gonneke, Williams, L Keoki, Ober, Carole, Hinds, David A, Ferreira, Manuel A, Bisgaard, Hans, Strachan, David P, and Bønnelykke, Klaus

Subjects
Biological Sciences, Genetics, Human Genome, Allergic Rhinitis (Hay Fever), Prevention, Biotechnology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Allergens, Case-Control Studies, Genetic Loci, Genetic Predisposition to Disease, Genetic Variation, Genome, Human, Genome-Wide Association Study, HLA Antigens, Humans, Phenotype, Rhinitis, Allergic, Risk, 23andMe Research Team, AAGC collaborators, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis.

Published
2018

19. Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function.

Author

Wyss, Annah B, Sofer, Tamar, Lee, Mi Kyeong, Terzikhan, Natalie, Nguyen, Jennifer N, Lahousse, Lies, Latourelle, Jeanne C, Smith, Albert Vernon, Bartz, Traci M, Feitosa, Mary F, Gao, Wei, Ahluwalia, Tarunveer S, Tang, Wenbo, Oldmeadow, Christopher, Duan, Qing, de Jong, Kim, Wojczynski, Mary K, Wang, Xin-Qun, Noordam, Raymond, Hartwig, Fernando Pires, Jackson, Victoria E, Wang, Tianyuan, Obeidat, Ma'en, Hobbs, Brian D, Huan, Tianxiao, Gui, Hongsheng, Parker, Margaret M, Hu, Donglei, Mogil, Lauren S, Kichaev, Gleb, Jin, Jianping, Graff, Mariaelisa, Harris, Tamara B, Kalhan, Ravi, Heckbert, Susan R, Paternoster, Lavinia, Burkart, Kristin M, Liu, Yongmei, Holliday, Elizabeth G, Wilson, James G, Vonk, Judith M, Sanders, Jason L, Barr, R Graham, de Mutsert, Renée, Menezes, Ana Maria Baptista, Adams, Hieab HH, van den Berge, Maarten, Joehanes, Roby, Levin, Albert M, Liberto, Jennifer, Launer, Lenore J, Morrison, Alanna C, Sitlani, Colleen M, Celedón, Juan C, Kritchevsky, Stephen B, Scott, Rodney J, Christensen, Kaare, Rotter, Jerome I, Bonten, Tobias N, Wehrmeister, Fernando César, Bossé, Yohan, Xiao, Shujie, Oh, Sam, Franceschini, Nora, Brody, Jennifer A, Kaplan, Robert C, Lohman, Kurt, McEvoy, Mark, Province, Michael A, Rosendaal, Frits R, Taylor, Kent D, Nickle, David C, Williams, L Keoki, Burchard, Esteban G, Wheeler, Heather E, Sin, Don D, Gudnason, Vilmundur, North, Kari E, Fornage, Myriam, Psaty, Bruce M, Myers, Richard H, O'Connor, George, Hansen, Torben, Laurie, Cathy C, Cassano, Patricia A, Sung, Joohon, Kim, Woo Jin, Attia, John R, Lange, Leslie, Boezen, H Marike, Thyagarajan, Bharat, Rich, Stephen S, Mook-Kanamori, Dennis O, Horta, Bernardo Lessa, Uitterlinden, André G, Im, Hae Kyung, Cho, Michael H, Brusselle, Guy G, and Gharib, Sina A

Subjects
Lung, Humans, Lung Diseases, Pulmonary Disease, Chronic Obstructive, Genetic Predisposition to Disease, Vital Capacity, Forced Expiratory Volume, Regression Analysis, Sample Size, Smoking, Genomics, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Quantitative Trait Loci, African Continental Ancestry Group, Asian Americans, European Continental Ancestry Group, Hispanic Americans, Female, Male, Genome-Wide Association Study, Polymorphism, Single Nucleotide, Pulmonary Disease, Chronic Obstructive
Abstract

Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of lung function and clinical relevance of implicated loci.

Published
2018

20. Whole-Genome Sequencing of Pharmacogenetic Drug Response in Racially Diverse Children with Asthma

Author

Mak, Angel CY, White, Marquitta J, Eckalbar, Walter L, Szpiech, Zachary A, Oh, Sam S, Pino-Yanes, Maria, Hu, Donglei, Goddard, Pagé, Huntsman, Scott, Galanter, Joshua, Wu, Ann Chen, Himes, Blanca E, Germer, Soren, Vogel, Julia M, Bunting, Karen L, Eng, Celeste, Salazar, Sandra, Keys, Kevin L, Liberto, Jennifer, Nuckton, Thomas J, Nguyen, Thomas A, Torgerson, Dara G, Kwok, Pui-Yan, Levin, Albert M, Celedón, Juan C, Forno, Erick, Hakonarson, Hakon, Sleiman, Patrick M, Dahlin, Amber, Tantisira, Kelan G, Weiss, Scott T, Serebrisky, Denise, Brigino-Buenaventura, Emerita, Farber, Harold J, Meade, Kelley, Lenoir, Michael A, Avila, Pedro C, Sen, Saunak, Thyne, Shannon M, Rodriguez-Cintron, William, Winkler, Cheryl A, Moreno-Estrada, Andrés, Sandoval, Karla, Rodriguez-Santana, Jose R, Kumar, Rajesh, Williams, L Keoki, Ahituv, Nadav, Ziv, Elad, Seibold, Max A, Darnell, Robert B, Zaitlen, Noah, Hernandez, Ryan D, and Burchard, Esteban G

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Health Disparities, Precision Medicine, Lung, Genetics, Asthma, Human Genome, Pediatric, Minority Health, Biotechnology, 2.1 Biological and endogenous factors, Respiratory, Good Health and Well Being, Adolescent, Black or African American, Albuterol, Bronchodilator Agents, Child, Female, Genome-Wide Association Study, Hispanic or Latino, Humans, Male, Mexican Americans, Pharmacogenomic Variants, Polymorphism, Single Nucleotide, Race Factors, United States, albuterol, asthma, minority, NFKB1, Latinos, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Medical and Health Sciences, Respiratory System, Cardiovascular medicine and haematology, Clinical sciences
Abstract

RationaleAlbuterol, a bronchodilator medication, is the first-line therapy for asthma worldwide. There are significant racial/ethnic differences in albuterol drug response.ObjectivesTo identify genetic variants important for bronchodilator drug response (BDR) in racially diverse children.MethodsWe performed the first whole-genome sequencing pharmacogenetics study from 1,441 children with asthma from the tails of the BDR distribution to identify genetic association with BDR.Measurements and main resultsWe identified population-specific and shared genetic variants associated with BDR, including genome-wide significant (P

Published
2018

21. The Impact of Environmental Benzene, Toluene, Ethylbenzene, and Xylene Exposure on Blood-Based DNA Methylation Profiles in Pregnant African American Women from Detroit

Author

Straughen, Jennifer K., primary, Loveless, Ian, additional, Chen, Yalei, additional, Burmeister, Charlotte, additional, Lamerato, Lois, additional, Lemke, Lawrence D., additional, O’Leary, Brendan F., additional, Reiners, John J., additional, Sperone, F. Gianluca, additional, Levin, Albert M., additional, and Cassidy-Bushrow, Andrea E., additional

Published
2024
Full Text
View/download PDF

22. Discovery and fine-mapping of adiposity loci using high density imputation of genome-wide association studies in individuals of African ancestry: African Ancestry Anthropometry Genetics Consortium.

Author

Ng, Maggie CY, Graff, Mariaelisa, Lu, Yingchang, Justice, Anne E, Mudgal, Poorva, Liu, Ching-Ti, Young, Kristin, Yanek, Lisa R, Feitosa, Mary F, Wojczynski, Mary K, Rand, Kristin, Brody, Jennifer A, Cade, Brian E, Dimitrov, Latchezar, Duan, Qing, Guo, Xiuqing, Lange, Leslie A, Nalls, Michael A, Okut, Hayrettin, Tajuddin, Salman M, Tayo, Bamidele O, Vedantam, Sailaja, Bradfield, Jonathan P, Chen, Guanjie, Chen, Wei-Min, Chesi, Alessandra, Irvin, Marguerite R, Padhukasahasram, Badri, Smith, Jennifer A, Zheng, Wei, Allison, Matthew A, Ambrosone, Christine B, Bandera, Elisa V, Bartz, Traci M, Berndt, Sonja I, Bernstein, Leslie, Blot, William J, Bottinger, Erwin P, Carpten, John, Chanock, Stephen J, Chen, Yii-Der Ida, Conti, David V, Cooper, Richard S, Fornage, Myriam, Freedman, Barry I, Garcia, Melissa, Goodman, Phyllis J, Hsu, Yu-Han H, Hu, Jennifer, Huff, Chad D, Ingles, Sue A, John, Esther M, Kittles, Rick, Klein, Eric, Li, Jin, McKnight, Barbara, Nayak, Uma, Nemesure, Barbara, Ogunniyi, Adesola, Olshan, Andrew, Press, Michael F, Rohde, Rebecca, Rybicki, Benjamin A, Salako, Babatunde, Sanderson, Maureen, Shao, Yaming, Siscovick, David S, Stanford, Janet L, Stevens, Victoria L, Stram, Alex, Strom, Sara S, Vaidya, Dhananjay, Witte, John S, Yao, Jie, Zhu, Xiaofeng, Ziegler, Regina G, Zonderman, Alan B, Adeyemo, Adebowale, Ambs, Stefan, Cushman, Mary, Faul, Jessica D, Hakonarson, Hakon, Levin, Albert M, Nathanson, Katherine L, Ware, Erin B, Weir, David R, Zhao, Wei, Zhi, Degui, Bone Mineral Density in Childhood Study (BMDCS) Group, Arnett, Donna K, Grant, Struan FA, Kardia, Sharon LR, Oloapde, Olufunmilayo I, Rao, DC, Rotimi, Charles N, Sale, Michele M, Williams, L Keoki, Zemel, Babette S, Becker, Diane M, and Borecki, Ingrid B

Subjects
Bone Mineral Density in Childhood Study (BMDCS) Group, Humans, Obesity, Genetic Predisposition to Disease, Serine Endopeptidases, Anthropometry, Body Mass Index, Waist-Hip Ratio, Chromosome Mapping, Gene Frequency, Linkage Disequilibrium, Polymorphism, Single Nucleotide, African Continental Ancestry Group, European Continental Ancestry Group, Female, Male, Adiposity, Genome-Wide Association Study, Transcription Factor 7-Like 2 Protein, Genetics, Human Genome, 2.1 Biological and endogenous factors, Developmental Biology
Abstract

Genome-wide association studies (GWAS) have identified >300 loci associated with measures of adiposity including body mass index (BMI) and waist-to-hip ratio (adjusted for BMI, WHRadjBMI), but few have been identified through screening of the African ancestry genomes. We performed large scale meta-analyses and replications in up to 52,895 individuals for BMI and up to 23,095 individuals for WHRadjBMI from the African Ancestry Anthropometry Genetics Consortium (AAAGC) using 1000 Genomes phase 1 imputed GWAS to improve coverage of both common and low frequency variants in the low linkage disequilibrium African ancestry genomes. In the sex-combined analyses, we identified one novel locus (TCF7L2/HABP2) for WHRadjBMI and eight previously established loci at P < 5×10-8: seven for BMI, and one for WHRadjBMI in African ancestry individuals. An additional novel locus (SPRYD7/DLEU2) was identified for WHRadjBMI when combined with European GWAS. In the sex-stratified analyses, we identified three novel loci for BMI (INTS10/LPL and MLC1 in men, IRX4/IRX2 in women) and four for WHRadjBMI (SSX2IP, CASC8, PDE3B and ZDHHC1/HSD11B2 in women) in individuals of African ancestry or both African and European ancestry. For four of the novel variants, the minor allele frequency was low (

Published
2017

23. Mutational Landscape of Aggressive Prostate Tumors in African American Men

Author

Lindquist, Karla J, Paris, Pamela L, Hoffmann, Thomas J, Cardin, Niall J, Kazma, Rémi, Mefford, Joel A, Simko, Jeffrey P, Ngo, Vy, Chen, Yalei, Levin, Albert M, Chitale, Dhananjay, Helfand, Brian T, Catalona, William J, Rybicki, Benjamin A, and Witte, John S

Subjects
Urologic Diseases, Clinical Research, Genetics, Prostate Cancer, Cancer, Human Genome, Aging, Black or African American, Humans, Male, Mutation, Prostatic Neoplasms, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

Prostate cancer is the most frequently diagnosed and second most fatal nonskin cancer among men in the United States. African American men are two times more likely to develop and die of prostate cancer compared with men of other ancestries. Previous whole genome or exome tumor-sequencing studies of prostate cancer have primarily focused on men of European ancestry. In this study, we sequenced and characterized somatic mutations in aggressive (Gleason ≥7, stage ≥T2b) prostate tumors from 24 African American patients. We describe the locations and prevalence of small somatic mutations (up to 50 bases in length), copy number aberrations, and structural rearrangements in the tumor genomes compared with patient-matched normal genomes. We observed several mutation patterns consistent with previous studies, such as large copy number aberrations in chromosome 8 and complex rearrangement chains. However, TMPRSS2-ERG gene fusions and PTEN losses occurred in only 21% and 8% of the African American patients, respectively, far less common than in patients of European ancestry. We also identified mutations that appeared specific to or more common in African American patients, including a novel CDC27-OAT gene fusion occurring in 17% of patients. The genomic aberrations reported in this study warrant further investigation of their biologic significant role in the incidence and clinical outcomes of prostate cancer in African Americans. Cancer Res; 76(7); 1860-8. ©2016 AACR.

Published
2016

24. Precocious infant fecal microbiome promotes enterocyte barrier dysfuction, altered neuroendocrine signaling and associates with increased childhood obesity risk

Author

Yong, Germaine J. M., primary, Porsche, Cara E., additional, Sitarik, Alexandra R., additional, Fujimura, Kei E., additional, McCauley, Kathryn, additional, Nguyen, Dat T., additional, Levin, Albert M., additional, Woodcroft, Kimberley J., additional, Ownby, Dennis R., additional, Rundle, Andrew G., additional, Johnson, Christine C., additional, Cassidy-Bushrow, Andrea, additional, and Lynch, Susan V., additional

Published
2023
Full Text
View/download PDF

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

Author

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

Published
2019
Full Text
View/download PDF

29. Genome-wide association study and admixture mapping reveal new loci associated with total IgE levels in Latinos

Author

Pino-Yanes, Maria, Gignoux, Christopher R, Galanter, Joshua M, Levin, Albert M, Campbell, Catarina D, Eng, Celeste, Huntsman, Scott, Nishimura, Katherine K, Gourraud, Pierre-Antoine, Mohajeri, Kiana, O'Roak, Brian J, Hu, Donglei, Mathias, Rasika A, Nguyen, Elizabeth A, Roth, Lindsey A, Padhukasahasram, Badri, Moreno-Estrada, Andres, Sandoval, Karla, Winkler, Cheryl A, Lurmann, Fred, Davis, Adam, Farber, Harold J, Meade, Kelley, Avila, Pedro C, Serebrisky, Denise, Chapela, Rocio, Ford, Jean G, Lenoir, Michael A, Thyne, Shannon M, Brigino-Buenaventura, Emerita, Borrell, Luisa N, Rodriguez-Cintron, William, Sen, Saunak, Kumar, Rajesh, Rodriguez-Santana, Jose R, Bustamante, Carlos D, Martinez, Fernando D, Raby, Benjamin A, Weiss, Scott T, Nicolae, Dan L, Ober, Carole, Meyers, Deborah A, Bleecker, Eugene R, Mack, Steven J, Hernandez, Ryan D, Eichler, Evan E, Barnes, Kathleen C, Williams, L Keoki, Torgerson, Dara G, and Burchard, Esteban G

Subjects
Biomedical and Clinical Sciences, Immunology, Clinical Research, Human Genome, Genetics, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Adolescent, Adult, Black or African American, Child, Chromosome Mapping, Chromosomes, Human, Pair 14, DNA-Binding Proteins, Female, Genetic Loci, Genome, Human, Genome-Wide Association Study, Genotype, HLA-DQ alpha-Chains, Hispanic or Latino, Humans, Immunoglobulin E, Male, Polymorphism, Single Nucleotide, Transcription Factors, White People, IgE, genome-wide association study, admixture mapping, allergy, asthma, next-generation sequencing, Latinos, Hispanics, minority populations, Allergy
Abstract

BackgroundIgE is a key mediator of allergic inflammation, and its levels are frequently increased in patients with allergic disorders.ObjectiveWe sought to identify genetic variants associated with IgE levels in Latinos.MethodsWe performed a genome-wide association study and admixture mapping of total IgE levels in 3334 Latinos from the Genes-environments & Admixture in Latino Americans (GALA II) study. Replication was evaluated in 454 Latinos, 1564 European Americans, and 3187 African Americans from independent studies.ResultsWe confirmed associations of 6 genes identified by means of previous genome-wide association studies and identified a novel genome-wide significant association of a polymorphism in the zinc finger protein 365 gene (ZNF365) with total IgE levels (rs200076616, P = 2.3 × 10(-8)). We next identified 4 admixture mapping peaks (6p21.32-p22.1, 13p22-31, 14q23.2, and 22q13.1) at which local African, European, and/or Native American ancestry was significantly associated with IgE levels. The most significant peak was 6p21.32-p22.1, where Native American ancestry was associated with lower IgE levels (P = 4.95 × 10(-8)). All but 22q13.1 were replicated in an independent sample of Latinos, and 2 of the peaks were replicated in African Americans (6p21.32-p22.1 and 14q23.2). Fine mapping of 6p21.32-p22.1 identified 6 genome-wide significant single nucleotide polymorphisms in Latinos, 2 of which replicated in European Americans. Another single nucleotide polymorphism was peak-wide significant within 14q23.2 in African Americans (rs1741099, P = 3.7 × 10(-6)) and replicated in non-African American samples (P = .011).ConclusionWe confirmed genetic associations at 6 genes and identified novel associations within ZNF365, HLA-DQA1, and 14q23.2. Our results highlight the importance of studying diverse multiethnic populations to uncover novel loci associated with total IgE levels.

Published
2015

30. Does Pet-Keeping Modify the Association of Delivery Mode with Offspring Body Size?

Author

Cassidy-Bushrow, Andrea E, Wegienka, Ganesa, Havstad, Suzanne, Levin, Albert M, Lynch, Susan V, Ownby, Dennis R, Rundle, Andrew G, Woodcroft, Kimberley J, Zoratti, Edward M, and Johnson, Christine Cole

Subjects
Reproductive Medicine, Biomedical and Clinical Sciences, Public Health, Health Sciences, Clinical Research, Pediatric, Nutrition, Obesity, Oral and gastrointestinal, Good Health and Well Being, Adult, Animals, Body Size, Cats, Cesarean Section, Child, Preschool, Delivery, Obstetric, Dogs, Female, Humans, Male, Middle Aged, Pediatric Obesity, Pets, Pregnancy, Risk Factors, Young Adult, Birth cohort, Childhood obesity, Delivery mode, Companion animals, Medical and Health Sciences, Studies in Human Society, Biomedical and clinical sciences, Health sciences, Human society
Abstract

Caesarean-section (CS) delivery increases risk of childhood obesity, and is associated with a distinct early-life gut microbiome, which may contribute to obesity. Household pets may alter human gut microbiome composition. We examined if pet-keeping modified the association of CS with obesity at age 2 years in 639 Wayne County Health, Environment, Allergy and Asthma Longitudinal Study birth cohort participants. Pet-keeping was defined as having a dog or cat (indoors ≥1 h/day) at child age 2 years. We used logistic regression to test for an interaction between CS and pet-keeping with obesity (BMI ≥ 95th percentile) at age 2 years, adjusted for maternal obesity. A total of 328 (51.3 %) children were male; 367 (57.4 %) were African American; 228 (35.7 %) were born by CS; and 55 (8.6 %) were obese. After adjusting for maternal obesity, CS-born children had a non-significant (P = 0.25) but elevated 1.4 (95 % CI 0.8, 2.5) higher odds of obesity compared to those born vaginally. There was evidence of effect modification between current pet-keeping and delivery mode with obesity at age 2 years (interaction P = 0.054). Compared to children born vaginally without a pet currently in the home, children born via CS without a pet currently in the home had a statistically significant (P = 0.043) higher odds (odds ratio 2.00; 95 % CI 1.02, 3.93) of being obese at age 2 years. Pets modified the CS-BMI relationship; whether the underlying mechanism is through effects on environmental or gut microbiome requires specific investigation.

Published
2015

31. Genome-wide interaction studies reveal sex-specific asthma risk alleles

Author

Myers, Rachel A, Scott, Nicole M, Gauderman, W James, Qiu, Weiliang, Mathias, Rasika A, Romieu, Isabelle, Levin, Albert M, Pino-Yanes, Maria, Graves, Penelope E, Villarreal, Albino Barraza, Beaty, Terri H, Carey, Vincent J, Croteau-Chonka, Damien C, del Rio Navarro, Blanca, Edlund, Christopher, Hernandez-Cadena, Leticia, Navarro-Olivos, Efrain, Padhukasahasram, Badri, Salam, Muhammad T, Torgerson, Dara G, Van den Berg, David J, Vora, Hita, Bleecker, Eugene R, Meyers, Deborah A, Williams, L Keoki, Martinez, Fernando D, Burchard, Esteban G, Barnes, Kathleen C, Gilliland, Frank D, Weiss, Scott T, London, Stephanie J, Raby, Benjamin A, Ober, Carole, Nicolae, Dan L, Santana, Jose Rodriguez, Cintron, William Rodriguez, Chapela, Rocio, Ford, Jean, Thyne, Shannon, Avila, Pedro C, Monge, Juan Jose Sienra, Boorgula, Meher, Cheadle, Chris, Eng, Celeste S, Kiley, J, Banks-Schlegel, S, and Gan, W

Subjects
Biological Sciences, Genetics, Clinical Research, Human Genome, Lung, Prevention, Asthma, Aetiology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Respiratory, Alleles, Chromosome Mapping, Female, Gene Expression Regulation, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Odds Ratio, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Racial Groups, Reproducibility of Results, Sex Factors, GRAAD, Continental Population Groups, Medical and Health Sciences, Genetics & Heredity
Abstract

Asthma is a complex disease with sex-specific differences in prevalence. Candidate gene studies have suggested that genotype-by-sex interaction effects on asthma risk exist, but this has not yet been explored at a genome-wide level. We aimed to identify sex-specific asthma risk alleles by performing a genome-wide scan for genotype-by-sex interactions in the ethnically diverse participants in the EVE Asthma Genetics Consortium. We performed male- and female-specific genome-wide association studies in 2653 male asthma cases, 2566 female asthma cases and 3830 non-asthma controls from European American, African American, African Caribbean and Latino populations. Association tests were conducted in each study sample, and the results were combined in ancestry-specific and cross-ancestry meta-analyses. Six sex-specific asthma risk loci had P-values < 1 × 10(-6), of which two were male specific and four were female specific; all were ancestry specific. The most significant sex-specific association in European Americans was at the interferon regulatory factor 1 (IRF1) locus on 5q31.1. We also identify a Latino female-specific association in RAP1GAP2. Both of these loci included single-nucleotide polymorphisms that are known expression quantitative trait loci and have been associated with asthma in independent studies. The IRF1 locus is a strong candidate region for male-specific asthma susceptibility due to the association and validation we demonstrate here, the known role of IRF1 in asthma-relevant immune pathways and prior reports of sex-specific differences in interferon responses.

Published
2014

32. Performance of the Genomic Evaluators of Metastatic Prostate Cancer (GEMCaP) Tumor Biomarker for Identifying Recurrent Disease in African American Patients

Author

Levin, Albert M, Lindquist, Karla J, Avila, Andrew, Witte, John S, Paris, Pamela L, and Rybicki, Benjamin A

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Urologic Diseases, Clinical Trials and Supportive Activities, Clinical Research, Cancer, Prostate Cancer, Human Genome, Genetics, Black or African American, Biomarkers, Tumor, Gene Dosage, Genomics, Humans, Male, Middle Aged, Neoplasm Metastasis, Neoplasm Recurrence, Local, Polymorphism, Single Nucleotide, Prognosis, Prostatic Neoplasms, Medical and Health Sciences, Epidemiology, Biomedical and clinical sciences, Health sciences
Abstract

Evaluation of prostate cancer prognosis after surgery is increasingly relying upon genomic analyses of tumor DNA. We assessed the ability of the biomarker panel Genomic Evaluators of Metastatic Prostate Cancer (GEMCaP) to predict biochemical recurrence in 33 European American and 28 African American prostate cancer cases using genome-wide copy number data from a previous study. "Biomarker positive" was defined as ≥20% of the 38 constituent copy number gain/loss GEMCaP loci affected in a given tumor; based on this threshold, the frequency of a positive biomarker was significantly lower in African Americans (n = 2; 7%) than European Americans (n = 11; 33%; P = 0.013). GEMCaP positivity was associated with risk of recurrence [hazard ratio (HR), 5.92; 95% confidence interval (CI), 2.32-15.11; P = 3 × 10(-4)] in the full sample and among European Americans (HR, 3.45; 95% CI, 1.13-10.51; P = 0.032) but was not estimable in African Americans due to the low rate of GEMCaP positivity. Overall, the GEMCaP recurrence positive predictive value (PPV) was 85%; in African Americans, PPV was 100%. When we expanded the definition of loss to include copy-neutral loss of heterozygosity (i.e., loss of one allele with concomitant duplication of the other), recurrence PPV was 83% for European American subjects. Under this definition, 5 African American subjects had a positive GEMCaP test value; 4 went on to develop biochemical recurrence (PPV = 80%). Our results suggest that the GEMCaP biomarker set could be an effective predictor for both European American and African American men diagnosed with localized prostate cancer who may benefit from immediate aggressive therapy after radical prostatectomy.

Published
2014

33. Nocturnal Asthma and the Importance of Race/Ethnicity and Genetic Ancestry

Author

Levin, Albert M, Wang, Yun, Wells, Karen E, Padhukasahasram, Badri, Yang, James J, Burchard, Esteban G, and Williams, L Keoki

Subjects
Clinical Research, Lung, Asthma, Genetics, Human Genome, Respiratory, Administration, Inhalation, Adult, African Americans, Albuterol, Body Mass Index, Bronchodilator Agents, Circadian Rhythm, Female, Forced Expiratory Volume, Genome-Wide Association Study, Humans, Logistic Models, Male, Michigan, Pharmacogenetics, Phenotype, Smoking, Surveys and Questionnaires, Whites, asthma, nocturnal symptoms, race/ethnicity, lung function, genetic ancestry, White People, Black or African American, Medical and Health Sciences, Respiratory System
Abstract

RationaleNocturnal asthma is a common presentation and is associated with a more severe form of the disease. However, there are few epidemiologic studies of nocturnal asthma, particularly in minority populations.ObjectivesTo identify factors associated with nocturnal asthma, including the contribution of self-identified race/ethnicity and genetic ancestry.MethodsThe analysis included individuals from the Study for Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE) cohort. Nocturnal asthma symptoms were assessed by questionnaire. Genome-wide genotype data were used to estimate genetic ancestry in a subset of African American participants. Logistic regression was used evaluate the association of various factors with nocturnal asthma, such as self-identified race/ethnicity and genetic ancestry.Measurement and main resultsThe study comprised 3,380 African American and 1,818 European Americans individuals with asthma. After adjusting for other potential explanatory variables, including controller medication use, African Americans were more than twice as likely (odds ratio, 2.56; 95% confidence interval, 2.24-2.93) to report nocturnal asthma when compared with European American individuals. Among the subset of African American participants with genome-wide genotype data (n = 1,040), estimated proportion of African ancestry was also associated with an increased risk of nocturnal asthma (P = 0.007). Differences in lung function explained a small, but statistically significant (P = 0.02), proportion of the relationship between genetic ancestry and nocturnal asthma symptoms.ConclusionsBoth self-identified race/ethnicity and African ancestry appear to be independent predictors of nocturnal asthma. The mechanism by which genetic ancestry contributes to population-level differences in nocturnal asthma appears to be largely independent of lung function.

Published
2014

34. Inclusivity in Research Matters: Variants in PVT1 Specific to Persons of African Descent Are Associated with Pulmonary Fibrosis.

Author

Garman, Lori, Pezant, Nathan, Dawkins, Bryan A., Rasmussen, Astrid, Levin, Albert M., Rybicki, Benjamin A., Iannuzzi, Michael C., Bagavant, Harini, Deshmukh, Umesh S., and Montgomery, Courtney G.

Subjects
SARCOIDOSIS, LINCRNA, PULMONARY function tests
Abstract

The article focuses on addressing the limited genetic studies of sarcoidosis-related pulmonary fibrosis (SPF) in individuals of African descent (AAs), with a particular emphasis on the lack of representation in previous studies. Topics include the leading cause of mortality in sarcoidosis, risk factors for pulmonary fibrosis, and the importance of conducting a whole-genome scan (WGS) to identify African-derived risk variants associated with SPF in underrepresented populations.

Published
2024
Full Text
View/download PDF

37. A meta-analysis of genome-wide association studies for serum total IgE in diverse study populations

Author

Levin, Albert M, Mathias, Rasika A, Huang, Lili, Roth, Lindsey A, Daley, Denise, Myers, Rachel A, Himes, Blanca E, Romieu, Isabelle, Yang, Mao, Eng, Celeste, Park, Julie E, Zoratti, Karla, Gignoux, Christopher R, Torgerson, Dara G, Galanter, Joshua M, Huntsman, Scott, Nguyen, Elizabeth A, Becker, Allan B, Chan-Yeung, Moira, Kozyrskyj, Anita L, Kwok, Pui-Yan, Gilliland, Frank D, Gauderman, W James, Bleecker, Eugene R, Raby, Benjamin A, Meyers, Deborah A, London, Stephanie J, Martinez, Fernando D, Weiss, Scott T, Burchard, Esteban G, Nicolae, Dan L, Ober, Carole, Barnes, Kathleen C, and Williams, L Keoki

Subjects
Biomedical and Clinical Sciences, Immunology, Lung, Human Genome, Clinical Research, Genetics, Asthma, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Adolescent, Adult, Black or African American, Aged, Aged, 80 and over, Canada, Case-Control Studies, Child, Child, Preschool, Female, Genome-Wide Association Study, HLA-DQ beta-Chains, Hispanic or Latino, Humans, Immunoglobulin E, Male, Middle Aged, Polymorphism, Single Nucleotide, United States, White People, Meta-analysis, genome-wide association study, total IgE, race-ethnicity, continental population groups, Allergy
Abstract

BackgroundIgE is both a marker and mediator of allergic inflammation. Despite reported differences in serum total IgE levels by race-ethnicity, African American and Latino subjects have not been well represented in genetic studies of total IgE.ObjectiveWe sought to identify the genetic predictors of serum total IgE levels.MethodsWe used genome-wide association data from 4292 subjects (2469 African Americans, 1564 European Americans, and 259 Latinos) in the EVE Asthma Genetics Consortium. Tests for association were performed within each cohort by race-ethnic group (ie, African American, Latino, and European American) and asthma status. The resulting P values were meta-analyzed, accounting for sample size and direction of effect. Top single nucleotide polymorphism associations from the meta-analysis were reassessed in 6 additional cohorts comprising 5767 subjects.ResultsWe identified 10 unique regions in which the combined association statistic was associated with total serum IgE levels (P

Published
2013

39. Assembly of a pan-genome from deep sequencing of 910 humans of African descent

Author

Sherman, Rachel M., Forman, Juliet, Antonescu, Valentin, Puiu, Daniela, Daya, Michelle, Rafaels, Nicholas, Boorgula, Meher Preethi, Chavan, Sameer, Vergara, Candelaria, Ortega, Victor E., Levin, Albert M., Eng, Celeste, Yazdanbakhsh, Maria, Wilson, James G., Marrugo, Javier, Lange, Leslie A., Williams, L. Keoki, Watson, Harold, Ware, Lorraine B., Olopade, Christopher O., Olopade, Olufunmilayo, Oliveira, Ricardo R., Ober, Carole, Nicolae, Dan L., Meyers, Deborah A., Mayorga, Alvaro, Knight-Madden, Jennifer, Hartert, Tina, Hansel, Nadia N., Foreman, Marilyn G., Ford, Jean G., Faruque, Mezbah U., Dunston, Georgia M., Caraballo, Luis, Burchard, Esteban G., Bleecker, Eugene R., Araujo, Maria I., Herrera-Paz, Edwin F., Campbell, Monica, Foster, Cassandra, Taub, Margaret A., Beaty, Terri H., Ruczinski, Ingo, Mathias, Rasika A., Barnes, Kathleen C., and Salzberg, Steven L.

Published
2019
Full Text
View/download PDF

40. Further replication studies of the EVE Consortium meta-analysis identifies 2 asthma risk loci in European Americans

Author

Myers, Rachel A, Himes, Blanca E, Gignoux, Christopher R, Yang, James J, Gauderman, W James, Rebordosa, Cristina, Xie, Jianming, Torgerson, Dara G, Levin, Albert M, Baurley, James, Graves, Penelope E, Mathias, Rasika A, Romieu, Isabelle, Roth, Lindsey A, Conti, David, Avila, Lydiana, Eng, Celeste, Vora, Hita, LeNoir, Michael A, Soto-Quiros, Manuel, Liu, Jinghua, Celedón, Juan C, Galanter, Joshua M, Farber, Harold J, Kumar, Rajesh, Avila, Pedro C, Meade, Kelley, Serebrisky, Denise, Thyne, Shannon, Rodriguez-Cintron, William, Rodriguez-Santana, Jose R, Borrell, Luisa N, Lemanske, Robert F, Bleecker, Eugene R, Meyers, Deborah A, London, Stephanie J, Barnes, Kathleen C, Raby, Benjamin A, Martinez, Fernando D, Gilliland, Frank D, Williams, L Keoki, Burchard, Esteban G, Weiss, Scott T, Nicolae, Dan L, and Ober, Carole

Subjects
Genetics, Asthma, Lung, Human Genome, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, Black or African American, Chromosomes, Human, Pair 19, DNA Mutational Analysis, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Hispanic or Latino, Humans, Kallikreins, Meta-Analysis as Topic, Polymorphism, Single Nucleotide, Prostate-Specific Antigen, Risk Factors, United States, White People, genetic risk factors, meta-analysis, KLK3, Immunology, Allergy
Abstract

BackgroundGenome-wide association studies of asthma have implicated many genetic risk factors, with well-replicated associations at approximately 10 loci that account for only a small proportion of the genetic risk.ObjectivesWe aimed to identify additional asthma risk loci by performing an extensive replication study of the results from the EVE Consortium meta-analysis.MethodsWe selected 3186 single nucleotide polymorphisms for replication based on the P values from the EVE Consortium meta-analysis. These single nucleotide polymorphisms were genotyped in ethnically diverse replication samples from 9 different studies, totaling 7202 cases, 6426 controls, and 507 case-parent trios. Association analyses were conducted within each participating study, and the resulting test statistics were combined in a meta-analysis.ResultsTwo novel associations were replicated in European Americans: rs1061477 in the KLK3 gene on chromosome 19 (combined odds ratio = 1.18; 95% CI, 1.10-1.25) and rs9570077 (combined odds ratio =1.20; 95% CI, 1.12-1.29) on chromosome 13q21. We could not replicate any additional associations in the African Americans or Latinos.ConclusionsThis extended replication study identified 2 additional asthma risk loci in populations of European descent. The absence of additional loci for African Americans and Latinos highlights the difficulty in replicating associations in admixed populations.

Published
2012

41. Genetic ancestry and its association with asthma exacerbations among African American subjects with asthma

Author

Rumpel, Jennifer A, Ahmedani, Brian K, Peterson, Edward L, Wells, Karen E, Yang, Mao, Levin, Albert M, Yang, James J, Kumar, Rajesh, Burchard, Esteban González, and Williams, L Keoki

Subjects
Biomedical and Clinical Sciences, Immunology, Asthma, Prevention, Lung, Clinical Research, Genetics, Respiratory, Adolescent, Adult, Black or African American, Aged, Child, Disease Progression, Emergency Service, Hospital, Female, Hospitalization, Humans, Insurance Claim Review, Male, Middle Aged, Risk, Sex Factors, United States, Young Adult, continental population groups, African continental ancestry group, genetic association study, health status disparities, minority health, Allergy
Abstract

BackgroundThere are large and persisting disparities in severe asthma exacerbations by race-ethnicity, and African American subjects are among those at greatest risk. It is unclear whether this increased risk solely represents differences in environmental exposures and health care or whether there is a predisposing genetic component.ObjectiveWe sought to assess the relationship between genetic ancestry and severe exacerbations among African American subjects with asthma.MethodsParticipants were part of the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE). These subjects were 12 to 56 years of age, received care from a single large health system, and had a physician's diagnosis of asthma. Genetic ancestry was estimated by using a set of validated ancestry informative markers. Severe exacerbations (ie, asthma-related emergency department visits, hospitalizations, and burst oral steroid use) were prospectively identified from health care claims.ResultsWe assessed genetic ancestry in 392 African American subjects with asthma. The average proportion of African ancestry was 76.1%. A significant interaction was identified between ancestry and sex on severe exacerbations, such that the risk was significantly higher with increasing African ancestry among male but not female subjects. The association among male subjects persisted after adjusting for potential confounders (relative rate, 4.30 for every 20% increase in African ancestry; P = .029).ConclusionsAfrican ancestry was significantly and positively associated with severe exacerbations among male African American subjects. These findings suggest that a portion of the risk of asthma exacerbations in this high-risk group is attributable to a genetic risk factor that partitions with ancestry.

Published
2012

42. Genetic variation in B cell–activating factor of the TNF family (BAFF) and asthma exacerbations among African American subjects

Author

Kumar, Rajesh, Williams, L Keoki, Kato, Atsushi, Peterson, Edward L, Favoreto, Silvio, Hulse, Katie, Wang, Deli, Beckman, Kenneth, Thyne, Shannon, LeNoir, Michael, Meade, Kelley, Lanfear, David E, Levin, Albert M, Favro, David, Yang, James J, Weiss, Kevin, Boushey, Homer A, Grammer, Leslie, Avila, Pedro C, Burchard, Esteban G, and Schleimer, Robert

Subjects
Biomedical and Clinical Sciences, Immunology, Black or African American, Asthma, B-Cell Activating Factor, Genetic Variation, Humans, Polymorphism, Single Nucleotide, Proportional Hazards Models, RNA, Messenger, Allergy
Abstract

A BAFF polymorphism is associated with asthma exacerbations and serum BAFF levels. BAFF expression in vivo increases in natural rhinovirus infection. BAFF may play a role in airway antiviral immunity and impact asthma exacerbation rates.

Published
2012

44. Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations.

Author

Torgerson, Dara G, Ampleford, Elizabeth J, Chiu, Grace Y, Gauderman, W James, Gignoux, Christopher R, Graves, Penelope E, Himes, Blanca E, Levin, Albert M, Mathias, Rasika A, Hancock, Dana B, Baurley, James W, Eng, Celeste, Stern, Debra A, Celedón, Juan C, Rafaels, Nicholas, Capurso, Daniel, Conti, David V, Roth, Lindsey A, Soto-Quiros, Manuel, Togias, Alkis, Li, Xingnan, Myers, Rachel A, Romieu, Isabelle, Van Den Berg, David J, Hu, Donglei, Hansel, Nadia N, Hernandez, Ryan D, Israel, Elliott, Salam, Muhammad T, Galanter, Joshua, Avila, Pedro C, Avila, Lydiana, Rodriquez-Santana, Jose R, Chapela, Rocio, Rodriguez-Cintron, William, Diette, Gregory B, Adkinson, N Franklin, Abel, Rebekah A, Ross, Kevin D, Shi, Min, Faruque, Mezbah U, Dunston, Georgia M, Watson, Harold R, Mantese, Vito J, Ezurum, Serpil C, Liang, Liming, Ruczinski, Ingo, Ford, Jean G, Huntsman, Scott, Chung, Kian Fan, Vora, Hita, Li, Xia, Calhoun, William J, Castro, Mario, Sienra-Monge, Juan J, del Rio-Navarro, Blanca, Deichmann, Klaus A, Heinzmann, Andrea, Wenzel, Sally E, Busse, William W, Gern, James E, Lemanske, Robert F, Beaty, Terri H, Bleecker, Eugene R, Raby, Benjamin A, Meyers, Deborah A, London, Stephanie J, Mexico City Childhood Asthma Study (MCAAS), Gilliland, Frank D, Children's Health Study (CHS) and HARBORS study, Burchard, Esteban G, Genetics of Asthma in Latino Americans (GALA) Study, Study of Genes-Environment and Admixture in Latino Americans (GALA2) and Study of African Americans, Asthma, Genes & Environments (SAGE), Martinez, Fernando D, Childhood Asthma Research and Education (CARE) Network, Weiss, Scott T, Childhood Asthma Management Program (CAMP), Williams, L Keoki, Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-Ethnicity (SAPPHIRE), Barnes, Kathleen C, Genetic Research on Asthma in African Diaspora (GRAAD) Study, Ober, Carole, and Nicolae, Dan L

Subjects
Mexico City Childhood Asthma Study, Children's Health Study (CHS) and HARBORS study, Genetics of Asthma in Latino Americans (GALA) Study, Study of Genes-Environment and Admixture in Latino Americans (GALA2) and Study of African Americans, Asthma, Genes & Environments, Childhood Asthma Research and Education (CARE) Network, Childhood Asthma Management Program, Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-Ethnicity, Genetic Research on Asthma in African Diaspora (GRAAD) Study, Humans, Asthma, Genetic Predisposition to Disease, Risk, African Americans, European Continental Ancestry Group, Hispanic Americans, Caribbean Region, North America, Genome-Wide Association Study, Genetic Loci, Genetics of Asthma in Latino Americans (GALA) Study, Study of Genes-Environment and Admixture in Latino Americans (GALA2) and Study of African Americans, Genes & Environments, Developmental Biology, Biological Sciences, Medical and Health Sciences
Abstract

Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent (P = 3.9 × 10(-9)). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma.

Published
2011

47. Data from Red Wine Consumption is Inversely Associated with 2-Amino-1-Methyl-6-Phenylimidazo[4,5-b]Pyridine–DNA Adduct Levels in Prostate

Author

Rybicki, Benjamin A., primary, Neslund-Dudas, Christine, primary, Bock, Cathryn H., primary, Nock, Nora L., primary, Rundle, Andrew, primary, Jankowski, Michelle, primary, Levin, Albert M., primary, Beebe-Dimmer, Jennifer, primary, Savera, Adnan T., primary, Takahashi, Satoru, primary, Shirai, Tomoyuki, primary, and Tang, Deliang, primary

Published
2023
Full Text
View/download PDF

48. Supplementary Methods, Tables 1 - 3 from Red Wine Consumption is Inversely Associated with 2-Amino-1-Methyl-6-Phenylimidazo[4,5-b]Pyridine–DNA Adduct Levels in Prostate

Author

Rybicki, Benjamin A., primary, Neslund-Dudas, Christine, primary, Bock, Cathryn H., primary, Nock, Nora L., primary, Rundle, Andrew, primary, Jankowski, Michelle, primary, Levin, Albert M., primary, Beebe-Dimmer, Jennifer, primary, Savera, Adnan T., primary, Takahashi, Satoru, primary, Shirai, Tomoyuki, primary, and Tang, Deliang, primary

Published
2023
Full Text
View/download PDF

50. Translational Research Techniques for the Facial Plastic Surgeon: An Overview.

Author

Mason, William, Levin, Albert M., Buhl, Katherine, Ouchi, Takahiro, Parker, Bianca, Tan, Jessica, Ashammakhi, Nureddin, and Jones, Lamont R.

Subjects
*TRANSLATIONAL research, *PLASTIC surgeons, *RESEARCH methodology, *TECHNOLOGICAL innovations, *TISSUE culture, *HEAD & neck cancer
Abstract

The field of facial plastic and reconstructive surgery (FPRS) is an incredibly diverse, multispecialty field that seeks innovative and novel solutions for the management of physical defects on the head and neck. To aid in the advancement of medical and surgical treatments for these defects, there has been a recent emphasis on the importance of translational research. With recent technological advancements, there are now a myriad of research techniques that are widely accessible for physician and scientist use in translational research. Such techniques include integrated multiomics, advanced cell culture and microfluidic tissue models, established animal models, and emerging computer models generated using bioinformatics. This study discusses these various research techniques and how they have and can be used for research in the context of various important diseases within the field of FPRS. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results