253 results on '"Kaplan, Robert C"'
Search Results
2. HIV, HIV-specific Factors and Myocardial Disease in Women
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Kato, Yoko, Ambale-Venkatesh, Bharath, Naveed, Mahim, Shitole, Sanyog G, Peng, Qi, Levsky, Jeffrey M, Haramati, Linda B, Ordovas, Karen, Noworolski, Susan M, Lee, Yoo Jin, Kim, Ryung S, Lazar, Jason M, Anastos, Kathryn, Tien, Phyllis C, Kaplan, Robert C, Lima, Joao AC, and Kizer, Jorge R
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,HIV/AIDS ,Clinical Research ,Infectious Diseases ,Heart Disease ,Prevention ,Cardiovascular ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Infection ,Good Health and Well Being ,HIV ,Women's Interagency HIV Study ,antiretroviral therapy ,cardiac magnetic resonance ,myocardial fibro-inflammation ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Clinical sciences - Abstract
BackgroundPeople with HIV (PWH) have an increased risk of cardiovascular disease (CVD). Cardiac magnetic resonance (CMR) has documented higher myocardial fibrosis, inflammation and steatosis in PWH, but studies have mostly relied on healthy volunteers as comparators and focused on men.MethodsWe investigated the associations of HIV and HIV-specific factors with CMR phenotypes in female participants enrolled in the Women's Interagency HIV Study's New York and San Francisco sites. Primary phenotypes included myocardial native (n) T1 (fibro-inflammation), extracellular volume fraction (ECV, fibrosis) and triglyceride content (steatosis). Associations were evaluated with multivariable linear regression, and results pooled or meta-analyzed across centers.ResultsAmong 261 women with HIV (WWH, total n = 362), 76.2% had undetectable viremia at CMR. For the 82.8% receiving continuous antiretroviral therapy (ART) in the preceding 5 years, adherence was 51.7%, and 71.3% failed to achieve persistent viral suppression (42.2% with peak viral load
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- 2024
3. Association of the gut microbiome with kidney function and damage in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
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Peters, Brandilyn A, Qi, Qibin, Usyk, Mykhaylo, Daviglus, Martha L, Cai, Jianwen, Franceschini, Nora, Lash, James P, Gellman, Marc D, Yu, Bing, Boerwinkle, Eric, Knight, Rob, Burk, Robert D, and Kaplan, Robert C
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Microbiology ,Biological Sciences ,Clinical Research ,Diabetes ,Nutrition ,Kidney Disease ,Renal and urogenital ,Good Health and Well Being ,Humans ,Cross-Sectional Studies ,Gastrointestinal Microbiome ,Hispanic or Latino ,Kidney ,Public Health ,Renal Insufficiency ,Chronic ,Gut microbiome ,chronic kidney disease ,glomerular filtration rate ,metabolites - Abstract
BackgroundThe gut microbiome is altered in chronic kidney disease (CKD), potentially contributing to CKD progression and co-morbidities, but population-based studies of the gut microbiome across a wide range of kidney function and damage are lacking.MethodsIn the Hispanic Community Health Study/Study of Latinos, gut microbiome was assessed by shotgun sequencing of stool (n = 2,438; 292 with suspected CKD). We examined cross-sectional associations of estimated glomerular filtration rate (eGFR), urinary albumin:creatinine (UAC) ratio, and CKD with gut microbiome features. Kidney trait-related microbiome features were interrogated for correlation with serum metabolites (n = 700), and associations of microbiome-related serum metabolites with kidney trait progression were examined in a prospective analysis (n = 3,635).ResultsHigher eGFR was associated with overall gut microbiome composition, greater abundance of species from Prevotella, Faecalibacterium, Roseburia, and Eubacterium, and microbial functions related to synthesis of long-chain fatty acids and carbamoyl-phosphate. Higher UAC ratio and CKD were related to lower gut microbiome diversity and altered overall microbiome composition only in participants without diabetes. Microbiome features related to better kidney health were associated with many serum metabolites (e.g., higher indolepropionate, beta-cryptoxanthin; lower imidazole propionate, deoxycholic acids, p-cresol glucuronide). Imidazole propionate, deoxycholic acid metabolites, and p-cresol glucuronide were associated with prospective reductions in eGFR and/or increases in UAC ratio over ~6 y.ConclusionsKidney function is a significant correlate of the gut microbiome, while the relationship of kidney damage with the gut microbiome depends on diabetes status. Gut microbiome metabolites may contribute to CKD progression.
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- 2023
4. Metabolomic Profiling of Cardiac Fibrosis and Steatosis in Women With or at Risk for HIV.
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Shitole, Sanyog G, Naveed, Mahim, Wang, Zheng, Wang, Tao, Kato, Yoko, Ambale-Venkatesh, Bharath, Kaplan, Robert C, Tien, Phyllis C, Anastos, Kathryn, Lazar, Jason M, Lima, João A C, Qi, Qibin, and Kizer, Jorge R
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Female ,Humans ,Phosphorylcholine ,HIV Infections: complications ,Cardiomyopathies: complications ,Heart Failure: complications ,Fatty Liver: complications ,Fibrosis ,Triglycerides - Abstract
Heart failure is a prevalent disorder whose prognosis remains poor despite advances in treatment. Women with or at risk for HIV may be particularly susceptible, yet the metabolic pathways that promote myocardial disease and heart failure in this context remain incompletely characterized.To evaluate the metabolomic signatures of cardiac magnetic resonance measured phenotypes, we used available plasma metabolomic measures from participants in the Women's Interagency HIV Study who underwent cardiac magnetic resonance imaging. Our primary outcomes were myocardial extracellular volume fraction (MECV) and intramyocardial triglyceride content (IMTG). We applied partial least squares and identified the top 10 lipid and polar metabolites associated with MECV and IMTG. We used multivariable linear regression to evaluate these metabolites' individual associations with each phenotype.The mean age of participants (n = 153) was 53 ± 7, 93% were Black or Hispanic, and 74% were HIV positive. Phenylacetylglutamine, a microbial metabolite, was positively associated with MECV after full adjustment and false discovery rate correction. Three phosphatidylcholine species, N-acetylaspartic acid, and a lysophosphatidylcholine species were inversely associated with IMTG, while prolylglycine, methionine sulfoxide, sphingosine, taurine, and phosphorylcholine were positively associated with this phenotype. We found no evidence of interaction by HIV for the observed associations, but there was effect modification by hepatitis C virus of taurine's and phosphorylcholine's associations with IMTG.Among women with or at risk for HIV, we related various lipid and polar metabolites to cardiac fibrosis or steatosis, of which phenylacetylglutamine, N-acetylaspartic acid, and prolylglycine are novel. These findings implicate plausible mechanisms that could be targetable for therapeutics.
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- 2023
5. Genetic risk prediction in Hispanics/Latinos: milestones, challenges, and social-ethical considerations
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Maldonado, Betzaida L., Piqué, Daniel G., Kaplan, Robert C., Claw, Katrina G., and Gignoux, Christopher R.
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- 2023
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6. Evaluating the use of blood pressure polygenic risk scores across race/ethnic background groups
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Kurniansyah, Nuzulul, Goodman, Matthew O, Khan, Alyna T, Wang, Jiongming, Feofanova, Elena, Bis, Joshua C, Wiggins, Kerri L, Huffman, Jennifer E, Kelly, Tanika, Elfassy, Tali, Guo, Xiuqing, Palmas, Walter, Lin, Henry J, Hwang, Shih-Jen, Gao, Yan, Young, Kendra, Kinney, Gregory L, Smith, Jennifer A, Yu, Bing, Liu, Simin, Wassertheil-Smoller, Sylvia, Manson, JoAnn E, Zhu, Xiaofeng, Chen, Yii-Der Ida, Lee, I-Te, Gu, C Charles, Lloyd-Jones, Donald M, Zöllner, Sebastian, Fornage, Myriam, Kooperberg, Charles, Correa, Adolfo, Psaty, Bruce M, Arnett, Donna K, Isasi, Carmen R, Rich, Stephen S, Kaplan, Robert C, Redline, Susan, Mitchell, Braxton D, Franceschini, Nora, Levy, Daniel, Rotter, Jerome I, Morrison, Alanna C, and Sofer, Tamar
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Human Genome ,Genetics ,Clinical Research ,Cardiovascular ,Good Health and Well Being ,Male ,Female ,Humans ,Blood Pressure ,Population Health ,Risk Factors ,Multifactorial Inheritance ,Ethnicity ,Genome-Wide Association Study ,Genetic Predisposition to Disease - Abstract
We assess performance and limitations of polygenic risk scores (PRSs) for multiple blood pressure (BP) phenotypes in diverse population groups. We compare "clumping-and-thresholding" (PRSice2) and LD-based (LDPred2) methods to construct PRSs from each of multiple GWAS, as well as multi-PRS approaches that sum PRSs with and without weights, including PRS-CSx. We use datasets from the MGB Biobank, TOPMed study, UK biobank, and from All of Us to train, assess, and validate PRSs in groups defined by self-reported race/ethnic background (Asian, Black, Hispanic/Latino, and White). For both SBP and DBP, the PRS-CSx based PRS, constructed as a weighted sum of PRSs developed from multiple independent GWAS, perform best across all race/ethnic backgrounds. Stratified analysis in All of Us shows that PRSs are better predictive of BP in females compared to males, individuals without obesity, and middle-aged (40-60 years) compared to older and younger individuals.
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- 2023
7. Genetic diversity fuels gene discovery for tobacco and alcohol use
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Saunders, Gretchen RB, Wang, Xingyan, Chen, Fang, Jang, Seon-Kyeong, Liu, Mengzhen, Wang, Chen, Gao, Shuang, Jiang, Yu, Khunsriraksakul, Chachrit, Otto, Jacqueline M, Addison, Clifton, Akiyama, Masato, Albert, Christine M, Aliev, Fazil, Alonso, Alvaro, Arnett, Donna K, Ashley-Koch, Allison E, Ashrani, Aneel A, Barnes, Kathleen C, Barr, R Graham, Bartz, Traci M, Becker, Diane M, Bielak, Lawrence F, Benjamin, Emelia J, Bis, Joshua C, Bjornsdottir, Gyda, Blangero, John, Bleecker, Eugene R, Boardman, Jason D, Boerwinkle, Eric, Boomsma, Dorret I, Boorgula, Meher Preethi, Bowden, Donald W, Brody, Jennifer A, Cade, Brian E, Chasman, Daniel I, Chavan, Sameer, Chen, Yii-Der Ida, Chen, Zhengming, Cheng, Iona, Cho, Michael H, Choquet, Hélène, Cole, John W, Cornelis, Marilyn C, Cucca, Francesco, Curran, Joanne E, de Andrade, Mariza, Dick, Danielle M, Docherty, Anna R, Duggirala, Ravindranath, Eaton, Charles B, Ehringer, Marissa A, Esko, Tõnu, Faul, Jessica D, Fernandes Silva, Lilian, Fiorillo, Edoardo, Fornage, Myriam, Freedman, Barry I, Gabrielsen, Maiken E, Garrett, Melanie E, Gharib, Sina A, Gieger, Christian, Gillespie, Nathan, Glahn, David C, Gordon, Scott D, Gu, Charles C, Gu, Dongfeng, Gudbjartsson, Daniel F, Guo, Xiuqing, Haessler, Jeffrey, Hall, Michael E, Haller, Toomas, Harris, Kathleen Mullan, He, Jiang, Herd, Pamela, Hewitt, John K, Hickie, Ian, Hidalgo, Bertha, Hokanson, John E, Hopfer, Christian, Hottenga, JoukeJan, Hou, Lifang, Huang, Hongyan, Hung, Yi-Jen, Hunter, David J, Hveem, Kristian, Hwang, Shih-Jen, Hwu, Chii-Min, Iacono, William, Irvin, Marguerite R, Jee, Yon Ho, Johnson, Eric O, Joo, Yoonjung Y, Jorgenson, Eric, Justice, Anne E, Kamatani, Yoichiro, Kaplan, Robert C, Kaprio, Jaakko, Kardia, Sharon LR, and Keller, Matthew C
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Genetics ,Alcoholism ,Alcohol Use and Health ,Prevention ,Human Genome ,Substance Misuse ,Aetiology ,2.1 Biological and endogenous factors ,Cancer ,Good Health and Well Being ,Humans ,Genetic Predisposition to Disease ,Genetic Variation ,Genome-Wide Association Study ,Multifactorial Inheritance ,Risk Factors ,Tobacco Use ,Alcohol Drinking ,Transcriptome ,Sample Size ,Genetic Loci ,Internationality ,Europe ,23andMe Research Team ,Biobank Japan Project ,General Science & Technology - Abstract
Tobacco and alcohol use are heritable behaviours associated with 15% and 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease and injury1-4. These substances are used across the globe, yet genome-wide association studies have focused largely on individuals of European ancestries5. Here we leveraged global genetic diversity across 3.4 million individuals from four major clines of global ancestry (approximately 21% non-European) to power the discovery and fine-mapping of genomic loci associated with tobacco and alcohol use, to inform function of these loci via ancestry-aware transcriptome-wide association studies, and to evaluate the genetic architecture and predictive power of polygenic risk within and across populations. We found that increases in sample size and genetic diversity improved locus identification and fine-mapping resolution, and that a large majority of the 3,823 associated variants (from 2,143 loci) showed consistent effect sizes across ancestry dimensions. However, polygenic risk scores developed in one ancestry performed poorly in others, highlighting the continued need to increase sample sizes of diverse ancestries to realize any potential benefit of polygenic prediction.
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- 2022
8. Correlations between complex human phenotypes vary by genetic background, gender, and environment
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Elgart, Michael, Goodman, Matthew O, Isasi, Carmen, Chen, Han, Morrison, Alanna C, de Vries, Paul S, Xu, Huichun, Manichaikul, Ani W, Guo, Xiuqing, Franceschini, Nora, Psaty, Bruce M, Rich, Stephen S, Rotter, Jerome I, Lloyd-Jones, Donald M, Fornage, Myriam, Correa, Adolfo, Heard-Costa, Nancy L, Vasan, Ramachandran S, Hernandez, Ryan, Kaplan, Robert C, Redline, Susan, Consortium, The Trans-Omics for Precision Medicine, and Sofer, Tamar
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Biomedical and Clinical Sciences ,Genetic Testing ,Clinical Research ,Genetics ,Good Health and Well Being ,Humans ,Male ,Female ,Phenotype ,Genetic Background ,Trans-Omics for Precision Medicine (TOPMed) Consortium ,Haseman-Elston regression ,Hispanic Community Health Study/Study of Latinos ,Trans-Omics in Precision Medicine ,admixed population ,genetic architecture ,genetic background ,genetic correlation ,heritability ,household correlation ,multi-ethnic ,Biomedical and clinical sciences - Abstract
We develop a closed-form Haseman-Elston estimator for genetic and environmental correlation coefficients between complex phenotypes, which we term HEc, that is as precise as GCTA yet ∼20× faster. We estimate genetic and environmental correlations between over 7,000 phenotype pairs in subgroups from the Trans-Omics in Precision Medicine (TOPMed) program. We demonstrate substantial differences in both heritabilities and genetic correlations for multiple phenotypes and phenotype pairs between individuals of self-reported Black, Hispanic/Latino, and White backgrounds. We similarly observe differences in many of the genetic and environmental correlations between genders. To estimate the contribution of genetics to the observed phenotypic correlation, we introduce "fractional genetic correlation" as the fraction of phenotypic correlation explained by genetics. Finally, we quantify the enrichment of correlations between phenotypic domains, each of which is comprised of multiple phenotypes. Altogether, we demonstrate that the observed correlations between complex human phenotypes depend on the genetic background of the individuals, their gender, and their environment.
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- 2022
9. Rare coding variants in RCN3 are associated with blood pressure
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He, Karen Y, Kelly, Tanika N, Wang, Heming, Liang, Jingjing, Zhu, Luke, Cade, Brian E, Assimes, Themistocles L, Becker, Lewis C, Beitelshees, Amber L, Bielak, Lawrence F, Bress, Adam P, Brody, Jennifer A, Chang, Yen-Pei Christy, Chang, Yi-Cheng, de Vries, Paul S, Duggirala, Ravindranath, Fox, Ervin R, Franceschini, Nora, Furniss, Anna L, Gao, Yan, Guo, Xiuqing, Haessler, Jeffrey, Hung, Yi-Jen, Hwang, Shih-Jen, Irvin, Marguerite Ryan, Kalyani, Rita R, Liu, Ching-Ti, Liu, Chunyu, Martin, Lisa Warsinger, Montasser, May E, Muntner, Paul M, Mwasongwe, Stanford, Naseri, Take, Palmas, Walter, Reupena, Muagututi’a Sefuiva, Rice, Kenneth M, Sheu, Wayne H-H, Shimbo, Daichi, Smith, Jennifer A, Snively, Beverly M, Yanek, Lisa R, Zhao, Wei, Blangero, John, Boerwinkle, Eric, Chen, Yii-Der Ida, Correa, Adolfo, Cupples, L Adrienne, Curran, Joanne E, Fornage, Myriam, He, Jiang, Hou, Lifang, Kaplan, Robert C, Kardia, Sharon LR, Kenny, Eimear E, Kooperberg, Charles, Lloyd-Jones, Donald, Loos, Ruth JF, Mathias, Rasika A, McGarvey, Stephen T, Mitchell, Braxton D, North, Kari E, Peyser, Patricia A, Psaty, Bruce M, Raffield, Laura M, Rao, DC, Redline, Susan, Reiner, Alex P, Rich, Stephen S, Rotter, Jerome I, Taylor, Kent D, Tracy, Russell, Vasan, Ramachandran S, Morrison, Alanna C, Levy, Daniel, Chakravarti, Aravinda, Arnett, Donna K, and Zhu, Xiaofeng
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Biological Sciences ,Genetics ,Cardiovascular ,Human Genome ,Clinical Research ,Aetiology ,2.1 Biological and endogenous factors ,Good Health and Well Being ,Blood Pressure ,Genetic Linkage ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Humans ,Polymorphism ,Single Nucleotide ,Precision Medicine ,Whole Genome Sequencing ,Rare variant analysis ,Blood pressure ,Whole genome sequencing ,Samoan Obesity ,Lifestyle and Genetic Adaptations Study (OLaGA) Group ,NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium ,Information and Computing Sciences ,Medical and Health Sciences ,Bioinformatics ,Biological sciences ,Biomedical and clinical sciences - Abstract
BackgroundWhile large genome-wide association studies have identified nearly one thousand loci associated with variation in blood pressure, rare variant identification is still a challenge. In family-based cohorts, genome-wide linkage scans have been successful in identifying rare genetic variants for blood pressure. This study aims to identify low frequency and rare genetic variants within previously reported linkage regions on chromosomes 1 and 19 in African American families from the Trans-Omics for Precision Medicine (TOPMed) program. Genetic association analyses weighted by linkage evidence were completed with whole genome sequencing data within and across TOPMed ancestral groups consisting of 60,388 individuals of European, African, East Asian, Hispanic, and Samoan ancestries.ResultsAssociations of low frequency and rare variants in RCN3 and multiple other genes were observed for blood pressure traits in TOPMed samples. The association of low frequency and rare coding variants in RCN3 was further replicated in UK Biobank samples (N = 403,522), and reached genome-wide significance for diastolic blood pressure (p = 2.01 × 10- 7).ConclusionsLow frequency and rare variants in RCN3 contributes blood pressure variation. This study demonstrates that focusing association analyses in linkage regions greatly reduces multiple-testing burden and improves power to identify novel rare variants associated with blood pressure traits.
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- 2022
10. Rare genetic variants explain missing heritability in smoking.
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Jang, Seon-Kyeong, Evans, Luke, Fialkowski, Allison, Arnett, Donna K, Ashley-Koch, Allison E, Barnes, Kathleen C, Becker, Diane M, Bis, Joshua C, Blangero, John, Bleecker, Eugene R, Boorgula, Meher Preethi, Bowden, Donald W, Brody, Jennifer A, Cade, Brian E, Jenkins, Brenda W Campbell, Carson, April P, Chavan, Sameer, Cupples, L Adrienne, Custer, Brian, Damrauer, Scott M, David, Sean P, de Andrade, Mariza, Dinardo, Carla L, Fingerlin, Tasha E, Fornage, Myriam, Freedman, Barry I, Garrett, Melanie E, Gharib, Sina A, Glahn, David C, Haessler, Jeffrey, Heckbert, Susan R, Hokanson, John E, Hou, Lifang, Hwang, Shih-Jen, Hyman, Matthew C, Judy, Renae, Justice, Anne E, Kaplan, Robert C, Kardia, Sharon LR, Kelly, Shannon, Kim, Wonji, Kooperberg, Charles, Levy, Daniel, Lloyd-Jones, Donald M, Loos, Ruth JF, Manichaikul, Ani W, Gladwin, Mark T, Martin, Lisa Warsinger, Nouraie, Mehdi, Melander, Olle, Meyers, Deborah A, Montgomery, Courtney G, North, Kari E, Oelsner, Elizabeth C, Palmer, Nicholette D, Payton, Marinelle, Peljto, Anna L, Peyser, Patricia A, Preuss, Michael, Psaty, Bruce M, Qiao, Dandi, Rader, Daniel J, Rafaels, Nicholas, Redline, Susan, Reed, Robert M, Reiner, Alexander P, Rich, Stephen S, Rotter, Jerome I, Schwartz, David A, Shadyab, Aladdin H, Silverman, Edwin K, Smith, Nicholas L, Smith, J Gustav, Smith, Albert V, Smith, Jennifer A, Tang, Weihong, Taylor, Kent D, Telen, Marilyn J, Vasan, Ramachandran S, Gordeuk, Victor R, Wang, Zhe, Wiggins, Kerri L, Yanek, Lisa R, Yang, Ivana V, Young, Kendra A, Young, Kristin L, Zhang, Yingze, Liu, Dajiang J, Keller, Matthew C, and Vrieze, Scott
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Smoking ,Gene Frequency ,Phenotype ,Polymorphism ,Single Nucleotide ,Genome-Wide Association Study ,Tobacco ,Genetics ,Tobacco Smoke and Health ,Human Genome ,Cancer - Abstract
Common genetic variants explain less variation in complex phenotypes than inferred from family-based studies, and there is a debate on the source of this 'missing heritability'. We investigated the contribution of rare genetic variants to tobacco use with whole-genome sequences from up to 26,257 unrelated individuals of European ancestries and 11,743 individuals of African ancestries. Across four smoking traits, single-nucleotide-polymorphism-based heritability ([Formula: see text]) was estimated from 0.13 to 0.28 (s.e., 0.10-0.13) in European ancestries, with 35-74% of it attributable to rare variants with minor allele frequencies between 0.01% and 1%. These heritability estimates are 1.5-4 times higher than past estimates based on common variants alone and accounted for 60% to 100% of our pedigree-based estimates of narrow-sense heritability ([Formula: see text], 0.18-0.34). In the African ancestry samples, [Formula: see text] was estimated from 0.03 to 0.33 (s.e., 0.09-0.14) across the four smoking traits. These results suggest that rare variants are important contributors to the heritability of smoking.
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- 2022
11. Gut Microbiota, Plasma Metabolomic Profiles, and Carotid Artery Atherosclerosis in HIV Infection
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Wang, Zheng, Peters, Brandilyn A, Usyk, Mykhaylo, Xing, Jiaqian, Hanna, David B, Wang, Tao, Post, Wendy S, Landay, Alan L, Hodis, Howard N, Weber, Kathleen, French, Audrey, Golub, Elizabeth T, Lazar, Jason, Gustafson, Deborah, Kassaye, Seble, Aouizerat, Bradley, Haberlen, Sabina, Malvestutto, Carlos, Budoff, Matthew, Wolinsky, Steven M, Sharma, Anjali, Anastos, Kathryn, Clish, Clary B, Kaplan, Robert C, Burk, Robert D, and Qi, Qibin
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Medical Biochemistry and Metabolomics ,Biomedical and Clinical Sciences ,Atherosclerosis ,HIV/AIDS ,Infectious Diseases ,Cardiovascular ,Clinical Research ,Prevention ,Aetiology ,2.2 Factors relating to the physical environment ,2.1 Biological and endogenous factors ,Infection ,Good Health and Well Being ,Carotid Arteries ,Carotid Artery Diseases ,Carotid Stenosis ,Cross-Sectional Studies ,Female ,Gastrointestinal Microbiome ,HIV Infections ,Humans ,Lysophosphatidylcholines ,Male ,Plaque ,Atherosclerotic ,atherosclerosis ,cardiovascular diseases ,diglycerides ,lipid metabolism ,lipidomics ,Cardiorespiratory Medicine and Haematology ,Clinical Sciences ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology ,Clinical sciences - Abstract
BackgroundAlterations in gut microbiota and blood metabolomic profiles have been implicated in HIV infection and cardiovascular disease. However, it remains unclear whether alterations in gut microbiota may contribute to disrupted host blood metabolomic profiles in relation to atherosclerosis, especially in the context of HIV infection.MethodsWe analyzed cross-sectional associations between gut microbiota features and carotid artery plaque in 361 women with or at high risk of HIV (67% HIV+), and further integrated plaque-associated microbial features with plasma lipidomic/metabolomic profiles. Furthermore, in 737 women and men, we examined prospective associations of baseline gut bacteria-associated lipidomic and metabolomic profiles with incident carotid artery plaque over 7-year follow-up.ResultsWe found 2 potentially pathogenic bacteria, Fusobacterium and Proteus, were associated with carotid artery plaque; while the beneficial butyrate producer Odoribacter was inversely associated with plaque. Fusobacterium and Proteus were associated with multiple lipids/metabolites which were clustered into 8 modules in network. A module comprised of 9 lysophosphatidylcholines and lysophosphatidylethanolamines and a module comprised of 9 diglycerides were associated with increased risk of carotid artery plaque (risk ratio [95% CI], 1.34 [1.09-1.64] and 1.24 [1.02-1.51] per SD increment, respectively). Functional analyses identified bacterial enzymes in lipid metabolism associated with these plasma lipids. In particular, phospholipase A1 and A2 are the key enzymes in the reactions producing lysophosphatidylcholines and lysophosphatidylethanolamines.ConclusionsAmong individuals with or at high risk of HIV infection, we identified altered gut microbiota and related functional capacities in the lipid metabolism associated with disrupted plasma lipidomic profiles and carotid artery atherosclerosis.
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- 2022
12. Insights From a Large-Scale Whole-Genome Sequencing Study of Systolic Blood Pressure, Diastolic Blood Pressure, and Hypertension
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Kelly, Tanika N, Sun, Xiao, He, Karen Y, Brown, Michael R, Taliun, Sarah A Gagliano, Hellwege, Jacklyn N, Irvin, Marguerite R, Mi, Xuenan, Brody, Jennifer A, Franceschini, Nora, Guo, Xiuqing, Hwang, Shih-Jen, de Vries, Paul S, Gao, Yan, Moscati, Arden, Nadkarni, Girish N, Yanek, Lisa R, Elfassy, Tali, Smith, Jennifer A, Chung, Ren-Hua, Beitelshees, Amber L, Patki, Amit, Aslibekyan, Stella, Blobner, Brandon M, Peralta, Juan M, Assimes, Themistocles L, Palmas, Walter R, Liu, Chunyu, Bress, Adam P, Huang, Zhijie, Becker, Lewis C, Hwa, Chii-Min, O’Connell, Jeffrey R, Carlson, Jenna C, Warren, Helen R, Das, Sayantan, Giri, Ayush, Martin, Lisa W, Johnson, W Craig, Fox, Ervin R, Bottinger, Erwin P, Razavi, Alexander C, Vaidya, Dhananjay, Chuang, Lee-Ming, Chang, Yen-Pei C, Naseri, Take, Jain, Deepti, Kang, Hyun Min, Hung, Adriana M, Srinivasasainagendra, Vinodh, Snively, Beverly M, Gu, Dongfeng, Montasser, May E, Reupena, Muagututi A Sefuiva, Heavner, Benjamin D, LeFaive, Jonathon, Hixson, James E, Rice, Kenneth M, Wang, Fei Fei, Nielsen, Jonas B, Huang, Jianfeng, Khan, Alyna T, Zhou, Wei, Nierenberg, Jovia L, Laurie, Cathy C, Armstrong, Nicole D, Shi, Mengyao, Pan, Yang, Stilp, Adrienne M, Emery, Leslie, Wong, Quenna, Hawley, Nicola L, Minster, Ryan L, Curran, Joanne E, Munroe, Patricia B, Weeks, Daniel E, North, Kari E, Tracy, Russell P, Kenny, Eimear E, Shimbo, Daichi, Chakravarti, Aravinda, Rich, Stephen S, Reiner, Alex P, Blangero, John, Redline, Susan, Mitchell, Braxton D, Rao, Dabeeru C, Chen, Yii-Der Ida, Kardia, Sharon LR, Kaplan, Robert C, Mathias, Rasika A, He, Jiang, Psaty, Bruce M, Fornage, Myriam, Loos, Ruth JF, Correa, Adolfo, Boerwinkle, Eric, Rotter, Jerome I, Kooperberg, Charles, and Edwards, Todd L
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Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Clinical Sciences ,Human Genome ,Genetics ,2.1 Biological and endogenous factors ,Aetiology ,Cardiovascular ,Good Health and Well Being ,Blood Pressure ,Genome-Wide Association Study ,Genomics ,Humans ,Hypertension ,Polymorphism ,Single Nucleotide ,Precision Medicine ,allele ,blood pressure ,genome ,hypertension ,whole genome sequencing ,Samoan Obesity ,Lifestyle ,and Genetic Adaptations Study (OLaGA) Group ,‡ NHLBI Trans-Omics for Precision Medicine TOPMed) Consortium ,Cardiorespiratory Medicine and Haematology ,Public Health and Health Services ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology ,Clinical sciences - Abstract
BackgroundThe availability of whole-genome sequencing data in large studies has enabled the assessment of coding and noncoding variants across the allele frequency spectrum for their associations with blood pressure.MethodsWe conducted a multiancestry whole-genome sequencing analysis of blood pressure among 51 456 Trans-Omics for Precision Medicine and Centers for Common Disease Genomics program participants (stage-1). Stage-2 analyses leveraged array data from UK Biobank (N=383 145), Million Veteran Program (N=318 891), and Reasons for Geographic and Racial Differences in Stroke (N=10 643) participants, along with whole-exome sequencing data from UK Biobank (N=199 631) participants.ResultsTwo blood pressure signals achieved genome-wide significance in meta-analyses of stage-1 and stage-2 single variant findings (P
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- 2022
13. Nutritional blood concentration biomarkers in the Hispanic Community Health Study/Study of Latinos: Measurement characteristics and power
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Boe, Lillian A., Mossavar-Rahmani, Yasmin, Sotres-Alvarez, Daniela, Daviglus, Martha L., Durazo-Arvizu, Ramon A., Thyagarajan, Bharat, Kaplan, Robert C., and Shaw, Pamela A.
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Statistics - Applications - Abstract
Measurement error is a major issue in self-reported diet that can distort diet-disease relationships. Use of blood concentration biomarkers has the potential to mitigate the subjective bias inherent in self-report. As part of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) baseline visit (2008-2011), self-reported diet was collected on all participants (N=16,415). Blood concentration biomarkers for carotenoids, tocopherols, retinol, vitamin B12 and folate were collected on a subset (N=476), as part of the Study of Latinos: Nutrition and Physical Activity Assessment Study (SOLNAS). We examine the relationship between biomarker levels, self-reported intake, Hispanic/Latino background, and other participant characteristics in this diverse cohort. We build regression calibration-based prediction equations for ten nutritional biomarkers and use a simulation to study the power of detecting a diet-disease association in a multivariable Cox model using a predicted concentration level. Good power was observed for some nutrients with high prediction model R2 values, but further research is needed to understand how best to realize the potential of these dietary biomarkers. This study provides a comprehensive examination of several nutritional biomarkers within the HCHS/SOL, characterizing their associations with subject characteristics and the influence of the measurement characteristics on the power to detect associations with health outcomes., Comment: 20 pages in main manuscript including 5 tables and 2 figures; 14 pages of supplement including 5 tables and 1 figure
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- 2021
14. Menopause Is Associated with an Altered Gut Microbiome and Estrobolome, with Implications for Adverse Cardiometabolic Risk in the Hispanic Community Health Study/Study of Latinos
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Peters, Brandilyn A, Lin, Juan, Qi, Qibin, Usyk, Mykhaylo, Isasi, Carmen R, Mossavar-Rahmani, Yasmin, Derby, Carol A, Santoro, Nanette, Perreira, Krista M, Daviglus, Martha L, Kominiarek, Michelle A, Cai, Jianwen, Knight, Rob, Burk, Robert D, and Kaplan, Robert C
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Genetics ,Human Genome ,Contraception/Reproduction ,Prevention ,Clinical Research ,Aging ,Estrogen ,Aetiology ,2.1 Biological and endogenous factors ,Good Health and Well Being ,Female ,Male ,Humans ,Gastrointestinal Microbiome ,Public Health ,Menopause ,Gonadal Steroid Hormones ,Hispanic or Latino ,Cardiovascular Diseases ,gut microbiome ,menopause - Abstract
Menopause is a pivotal period during which loss of ovarian hormones increases cardiometabolic risk and may also influence the gut microbiome. However, the menopause-microbiome relationship has not been examined in a large study, and its implications for cardiometabolic disease are unknown. In the Hispanic Community Health Study/Study of Latinos, a population with high burden of cardiometabolic risk factors, shotgun metagenomic sequencing was performed on stool from 2,300 participants (295 premenopausal women, 1,027 postmenopausal women, and 978 men), and serum metabolomics was available on a subset. Postmenopausal women trended toward lower gut microbiome diversity and altered overall composition compared to premenopausal women, while differing less from men, in models adjusted for age and other demographic/behavioral covariates. Differentially abundant taxa for post- versus premenopausal women included Bacteroides sp. strain Ga6A1, Prevotella marshii, and Sutterella wadsworthensis (enriched in postmenopause) and Escherichia coli-Shigella spp., Oscillibacter sp. strain KLE1745, Akkermansia muciniphila, Clostridium lactatifermentans, Parabacteroides johnsonii, and Veillonella seminalis (depleted in postmenopause); these taxa similarly differed between men and women. Postmenopausal women had higher abundance of the microbial sulfate transport system and decreased abundance of microbial β-glucuronidase; these functions correlated with serum progestin metabolites, suggesting involvement of postmenopausal gut microbes in sex hormone retention. In postmenopausal women, menopause-related microbiome alterations were associated with adverse cardiometabolic profiles. In summary, in a large U.S. Hispanic/Latino population, menopause is associated with a gut microbiome more similar to that of men, perhaps related to the common condition of a low estrogen/progesterone state. Future work should examine similarity of results in other racial/ethnic groups. IMPORTANCE The menopausal transition, marked by declining ovarian hormones, is recognized as a pivotal period of cardiometabolic risk. Gut microbiota metabolically interact with sex hormones, but large population studies associating menopause with the gut microbiome are lacking. Our results from a large study of Hispanic/Latino women and men suggest that the postmenopausal gut microbiome in women is slightly more similar to the gut microbiome in men and that menopause depletes specific gut pathogens and decreases the hormone-related metabolic potential of the gut microbiome. At the same time, gut microbes may participate in sex hormone reactivation and retention in postmenopausal women. Menopause-related gut microbiome changes were associated with adverse cardiometabolic risk in postmenopausal women, indicating that the gut microbiome contributes to changes in cardiometabolic health during menopause.
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- 2022
15. Collaborative Cohort of Cohorts for COVID-19 Research (C4R) Study: Study Design
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Oelsner, Elizabeth C, Krishnaswamy, Akshaya, Balte, Pallavi P, Allen, Norrina Bai, Ali, Tauqeer, Anugu, Pramod, Andrews, Howard F, Arora, Komal, Asaro, Alyssa, Barr, R Graham, Bertoni, Alain G, Bon, Jessica, Boyle, Rebekah, Chang, Arunee A, Chen, Grace, Coady, Sean, Cole, Shelley A, Coresh, Josef, Cornell, Elaine, Correa, Adolfo, Couper, David, Cushman, Mary, Demmer, Ryan T, Elkind, Mitchell SV, Folsom, Aaron R, Fretts, Amanda M, Gabriel, Kelley P, Gallo, Linda C, Gutierrez, Jose, Han, Mei Lan K, Henderson, Joel M, Howard, Virginia J, Isasi, Carmen R, Jacobs, David R, Judd, Suzanne E, Mukaz, Debora Kamin, Kanaya, Alka M, Kandula, Namratha R, Kaplan, Robert C, Kinney, Gregory L, Kucharska-Newton, Anna, Lee, Joyce S, Lewis, Cora E, Levine, Deborah A, Levitan, Emily B, Levy, Bruce D, Make, Barry J, Malloy, Kimberly, Manly, Jennifer J, Mendoza-Puccini, Carolina, Meyer, Katie A, Min, Yuan-I Nancy, Moll, Matthew R, Moore, Wendy C, Mauger, David, Ortega, Victor E, Palta, Priya, Parker, Monica M, Phipatanakul, Wanda, Post, Wendy S, Postow, Lisa, Psaty, Bruce M, Regan, Elizabeth A, Ring, Kimberly, Roger, Véronique L, Rotter, Jerome I, Rundek, Tatjana, Sacco, Ralph L, Schembri, Michael, Schwartz, David A, Seshadri, Sudha, Shikany, James M, Sims, Mario, Stukovsky, Karen D Hinckley, Talavera, Gregory A, Tracy, Russell P, Umans, Jason G, Vasan, Ramachandran S, Watson, Karol E, Wenzel, Sally E, Winters, Karen, Woodruff, Prescott G, Xanthakis, Vanessa, Zhang, Ying, Zhang, Yiyi, and Investigators, for the C4R
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Public Health ,Health Sciences ,Social Determinants of Health ,Basic Behavioral and Social Science ,Coronaviruses Disparities and At-Risk Populations ,Prevention ,Coronaviruses ,Infectious Diseases ,Clinical Research ,Emerging Infectious Diseases ,Behavioral and Social Science ,Aetiology ,2.4 Surveillance and distribution ,Good Health and Well Being ,Adolescent ,Adult ,Aged ,Aged ,80 and over ,COVID-19 ,Cohort Studies ,Humans ,Middle Aged ,Pandemics ,Prospective Studies ,SARS-CoV-2 ,United States ,Young Adult ,cohort studies ,coronavirus disease 2019 ,severe acute respiratory syndrome coronavirus 2 ,%22">> ,C4R Investigators ,severe acute respiratory syndrome coronavirus 2 ,Mathematical Sciences ,Medical and Health Sciences ,Epidemiology - Abstract
The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults comprising 14 established US prospective cohort studies. Starting as early as 1971, investigators in the C4R cohort studies have collected data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R links this pre-coronavirus disease 2019 (COVID-19) phenotyping to information on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and acute and postacute COVID-related illness. C4R is largely population-based, has an age range of 18-108 years, and reflects the racial, ethnic, socioeconomic, and geographic diversity of the United States. C4R ascertains SARS-CoV-2 infection and COVID-19 illness using standardized questionnaires, ascertainment of COVID-related hospitalizations and deaths, and a SARS-CoV-2 serosurvey conducted via dried blood spots. Master protocols leverage existing robust retention rates for telephone and in-person examinations and high-quality event surveillance. Extensive prepandemic data minimize referral, survival, and recall bias. Data are harmonized with research-quality phenotyping unmatched by clinical and survey-based studies; these data will be pooled and shared widely to expedite collaboration and scientific findings. This resource will allow evaluation of risk and resilience factors for COVID-19 severity and outcomes, including postacute sequelae, and assessment of the social and behavioral impact of the pandemic on long-term health trajectories.
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- 2022
16. Host and gut microbial tryptophan metabolism and type 2 diabetes: an integrative analysis of host genetics, diet, gut microbiome and circulating metabolites in cohort studies
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Qi, Qibin, Li, Jun, Yu, Bing, Moon, Jee-Young, Chai, Jin C, Merino, Jordi, Hu, Jie, Ruiz-Canela, Miguel, Rebholz, Casey, Wang, Zheng, Usyk, Mykhaylo, Chen, Guo-Chong, Porneala, Bianca C, Wang, Wenshuang, Nguyen, Ngoc Quynh, Feofanova, Elena V, Grove, Megan L, Wang, Thomas J, Gerszten, Robert E, Dupuis, Josée, Salas-Salvadó, Jordi, Bao, Wei, Perkins, David L, Daviglus, Martha L, Thyagarajan, Bharat, Cai, Jianwen, Wang, Tao, Manson, JoAnn E, Martínez-González, Miguel A, Selvin, Elizabeth, Rexrode, Kathryn M, Clish, Clary B, Hu, Frank B, Meigs, James B, Knight, Rob, Burk, Robert D, Boerwinkle, Eric, and Kaplan, Robert C
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Obesity ,Human Genome ,Prevention ,Genetics ,Nutrition ,Diabetes ,2.2 Factors relating to the physical environment ,Aetiology ,Metabolic and endocrine ,Oral and gastrointestinal ,Bacteria ,Cohort Studies ,Diabetes Mellitus ,Type 2 ,Diet ,Gastrointestinal Microbiome ,Humans ,Kynurenine ,Lactase ,Tryptophan ,diabetes mellitus ,dietary factors ,genetics ,Clinical Sciences ,Paediatrics and Reproductive Medicine ,Gastroenterology & Hepatology - Abstract
ObjectiveTryptophan can be catabolised to various metabolites through host kynurenine and microbial indole pathways. We aimed to examine relationships of host and microbial tryptophan metabolites with incident type 2 diabetes (T2D), host genetics, diet and gut microbiota.MethodWe analysed associations between circulating levels of 11 tryptophan metabolites and incident T2D in 9180 participants of diverse racial/ethnic backgrounds from five cohorts. We examined host genome-wide variants, dietary intake and gut microbiome associated with these metabolites.ResultsTryptophan, four kynurenine-pathway metabolites (kynurenine, kynurenate, xanthurenate and quinolinate) and indolelactate were positively associated with T2D risk, while indolepropionate was inversely associated with T2D risk. We identified multiple host genetic variants, dietary factors, gut bacteria and their potential interplay associated with these T2D-relaetd metabolites. Intakes of fibre-rich foods, but not protein/tryptophan-rich foods, were the dietary factors most strongly associated with tryptophan metabolites. The fibre-indolepropionate association was partially explained by indolepropionate-associated gut bacteria, mostly fibre-using Firmicutes. We identified a novel association between a host functional LCT variant (determining lactase persistence) and serum indolepropionate, which might be related to a host gene-diet interaction on gut Bifidobacterium, a probiotic bacterium significantly associated with indolepropionate independent of other fibre-related bacteria. Higher milk intake was associated with higher levels of gut Bifidobacterium and serum indolepropionate only among genetically lactase non-persistent individuals.ConclusionHigher milk intake among lactase non-persistent individuals, and higher fibre intake were associated with a favourable profile of circulating tryptophan metabolites for T2D, potentially through the host-microbial cross-talk shifting tryptophan metabolism toward gut microbial indolepropionate production.
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- 2022
17. Polygenic transcriptome risk scores for COPD and lung function improve cross-ethnic portability of prediction in the NHLBI TOPMed program
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Hu, Xiaowei, Qiao, Dandi, Kim, Wonji, Moll, Matthew, Balte, Pallavi P, Lange, Leslie A, Bartz, Traci M, Kumar, Rajesh, Li, Xingnan, Yu, Bing, Cade, Brian E, Laurie, Cecelia A, Sofer, Tamar, Ruczinski, Ingo, Nickerson, Deborah A, Muzny, Donna M, Metcalf, Ginger A, Doddapaneni, Harshavardhan, Gabriel, Stacy, Gupta, Namrata, Dugan-Perez, Shannon, Cupples, L Adrienne, Loehr, Laura R, Jain, Deepti, Rotter, Jerome I, Wilson, James G, Psaty, Bruce M, Fornage, Myriam, Morrison, Alanna C, Vasan, Ramachandran S, Washko, George, Rich, Stephen S, O’Connor, George T, Bleecker, Eugene, Kaplan, Robert C, Kalhan, Ravi, Redline, Susan, Gharib, Sina A, Meyers, Deborah, Ortega, Victor, Dupuis, Josée, London, Stephanie J, Lappalainen, Tuuli, Oelsner, Elizabeth C, Silverman, Edwin K, Barr, R Graham, Thornton, Timothy A, Wheeler, Heather E, Group, TOPMed Lung Working, Cho, Michael H, Im, Hae Kyung, and Manichaikul, Ani
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Epidemiology ,Biological Sciences ,Health Sciences ,Genetics ,Clinical Research ,Lung ,Prevention ,Tobacco ,Chronic Obstructive Pulmonary Disease ,Tobacco Smoke and Health ,Respiratory ,Good Health and Well Being ,Humans ,National Heart ,Lung ,and Blood Institute (U.S.) ,Pulmonary Disease ,Chronic Obstructive ,Risk Factors ,Transcriptome ,United States ,TOPMed Lung Working Group ,cross-ethnic portability ,gene expression ,integrative analysis ,polygenic transcriptome risk score ,pulmonary disease ,risk prediction ,Medical and Health Sciences ,Genetics & Heredity ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
While polygenic risk scores (PRSs) enable early identification of genetic risk for chronic obstructive pulmonary disease (COPD), predictive performance is limited when the discovery and target populations are not well matched. Hypothesizing that the biological mechanisms of disease are shared across ancestry groups, we introduce a PrediXcan-derived polygenic transcriptome risk score (PTRS) to improve cross-ethnic portability of risk prediction. We constructed the PTRS using summary statistics from application of PrediXcan on large-scale GWASs of lung function (forced expiratory volume in 1 s [FEV1] and its ratio to forced vital capacity [FEV1/FVC]) in the UK Biobank. We examined prediction performance and cross-ethnic portability of PTRS through smoking-stratified analyses both on 29,381 multi-ethnic participants from TOPMed population/family-based cohorts and on 11,771 multi-ethnic participants from TOPMed COPD-enriched studies. Analyses were carried out for two dichotomous COPD traits (moderate-to-severe and severe COPD) and two quantitative lung function traits (FEV1 and FEV1/FVC). While the proposed PTRS showed weaker associations with disease than PRS for European ancestry, the PTRS showed stronger association with COPD than PRS for African Americans (e.g., odds ratio [OR] = 1.24 [95% confidence interval [CI]: 1.08-1.43] for PTRS versus 1.10 [0.96-1.26] for PRS among heavy smokers with ≥ 40 pack-years of smoking) for moderate-to-severe COPD. Cross-ethnic portability of the PTRS was significantly higher than the PRS (paired t test p
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- 2022
18. Characterizing longitudinal change in accelerometry-based moderate-to-vigorous physical activity in the Hispanic Community Health Study/Study of Latinos and the Framingham Heart Study
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Mossavar-Rahmani, Yasmin, Lin, Juan, Pan, Stephanie, Song, Rebecca J., Xue, Xiaonan, Spartano, Nicole L., Xanthakis, Vanessa, Sotres-Alvarez, Daniela, Marquez, David X., Daviglus, Martha, Carlson, Jordan A., Parada, Jr, Humberto, Evenson, Kelly R., Talavera, Ana C., Gellman, Marc, Perreira, Krista M., Gallo, Linda C., Vasan, Ramachandran S., and Kaplan, Robert C.
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- 2023
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19. Gut microbiota, circulating inflammatory markers and metabolites, and carotid artery atherosclerosis in HIV infection
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Wang, Zheng, Peters, Brandilyn A., Bryant, MacKenzie, Hanna, David B., Schwartz, Tara, Wang, Tao, Sollecito, Christopher C., Usyk, Mykhaylo, Grassi, Evan, Wiek, Fanua, Peter, Lauren St., Post, Wendy S., Landay, Alan L., Hodis, Howard N., Weber, Kathleen M., French, Audrey, Golub, Elizabeth T., Lazar, Jason, Gustafson, Deborah, Sharma, Anjali, Anastos, Kathryn, Clish, Clary B., Burk, Robert D., Kaplan, Robert C., Knight, Rob, and Qi, Qibin
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- 2023
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20. Kernel-based genetic association analysis for microbiome phenotypes identifies host genetic drivers of beta-diversity
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Liu, Hongjiao, Ling, Wodan, Hua, Xing, Moon, Jee-Young, Williams-Nguyen, Jessica S., Zhan, Xiang, Plantinga, Anna M., Zhao, Ni, Zhang, Angela, Knight, Rob, Qi, Qibin, Burk, Robert D., Kaplan, Robert C., and Wu, Michael C.
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- 2023
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21. Mendelian randomization supports bidirectional causality between telomere length and clonal hematopoiesis of indeterminate potential
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Nakao, Tetsushi, Bick, Alexander G, Taub, Margaret A, Zekavat, Seyedeh M, Uddin, Md M, Niroula, Abhishek, Carty, Cara L, Lane, John, Honigberg, Michael C, Weinstock, Joshua S, Pampana, Akhil, Gibson, Christopher J, Griffin, Gabriel K, Clarke, Shoa L, Bhattacharya, Romit, Assimes, Themistocles L, Emery, Leslie S, Stilp, Adrienne M, Wong, Quenna, Broome, Jai, Laurie, Cecelia A, Khan, Alyna T, Smith, Albert V, Blackwell, Thomas W, Codd, Veryan, Nelson, Christopher P, Yoneda, Zachary T, Peralta, Juan M, Bowden, Donald W, Irvin, Marguerite R, Boorgula, Meher, Zhao, Wei, Yanek, Lisa R, Wiggins, Kerri L, Hixson, James E, Gu, C Charles, Peloso, Gina M, Roden, Dan M, Reupena, Muagututi’a S, Hwu, Chii-Min, DeMeo, Dawn L, North, Kari E, Kelly, Shannon, Musani, Solomon K, Bis, Joshua C, Lloyd-Jones, Donald M, Johnsen, Jill M, Preuss, Michael, Tracy, Russell P, Peyser, Patricia A, Qiao, Dandi, Desai, Pinkal, Curran, Joanne E, Freedman, Barry I, Tiwari, Hemant K, Chavan, Sameer, Smith, Jennifer A, Smith, Nicholas L, Kelly, Tanika N, Hidalgo, Bertha, Cupples, L Adrienne, Weeks, Daniel E, Hawley, Nicola L, Minster, Ryan L, Deka, Ranjan, Naseri, Take T, de las Fuentes, Lisa, Raffield, Laura M, Morrison, Alanna C, Vries, Paul S, Ballantyne, Christie M, Kenny, Eimear E, Rich, Stephen S, Whitsel, Eric A, Cho, Michael H, Shoemaker, M Benjamin, Pace, Betty S, Blangero, John, Palmer, Nicholette D, Mitchell, Braxton D, Shuldiner, Alan R, Barnes, Kathleen C, Redline, Susan, Kardia, Sharon LR, Abecasis, Gonçalo R, Becker, Lewis C, Heckbert, Susan R, He, Jiang, Post, Wendy, Arnett, Donna K, Vasan, Ramachandran S, Darbar, Dawood, Weiss, Scott T, McGarvey, Stephen T, de Andrade, Mariza, Chen, Yii-Der Ida, Kaplan, Robert C, Meyers, Deborah A, Custer, Brian S, and Correa, Adolfo
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Cardiovascular ,Genetics ,Aging ,Heart Disease ,Heart Disease - Coronary Heart Disease ,Human Genome ,Atherosclerosis ,Aetiology ,2.1 Biological and endogenous factors ,Good Health and Well Being ,Samoan Obesity ,Lifestyle and Genetic Adaptations Study (OLaGA) Group ,NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium - Abstract
Human genetic studies support an inverse causal relationship between leukocyte telomere length (LTL) and coronary artery disease (CAD), but directionally mixed effects for LTL and diverse malignancies. Clonal hematopoiesis of indeterminate potential (CHIP), characterized by expansion of hematopoietic cells bearing leukemogenic mutations, predisposes both hematologic malignancy and CAD. TERT (which encodes telomerase reverse transcriptase) is the most significantly associated germline locus for CHIP in genome-wide association studies. Here, we investigated the relationship between CHIP, LTL, and CAD in the Trans-Omics for Precision Medicine (TOPMed) program (n = 63,302) and UK Biobank (n = 47,080). Bidirectional Mendelian randomization studies were consistent with longer genetically imputed LTL increasing propensity to develop CHIP, but CHIP then, in turn, hastens to shorten measured LTL (mLTL). We also demonstrated evidence of modest mediation between CHIP and CAD by mLTL. Our data promote an understanding of potential causal relationships across CHIP and LTL toward prevention of CAD.
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- 2022
22. Menopause Is Associated With Immune Activation in Women With HIV
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Peters, Brandilyn A, Xue, Xiaonan, Sheira, Lila A, Qi, Qibin, Sharma, Anjali, Santoro, Nanette, Alcaide, Maria L, Ofotokun, Igho, Adimora, Adaora A, McKay, Heather S, Tien, Phyllis C, Michel, Katherine G, Gustafson, Deborah, Turan, Bulent, Landay, Alan L, Kaplan, Robert C, and Weiser, Sheri D
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Biomedical and Clinical Sciences ,Immunology ,Infectious Diseases ,HIV/AIDS ,Sexually Transmitted Infections ,Aging ,Estrogen ,Contraception/Reproduction ,Infection ,Biomarkers ,Female ,HIV Infections ,Humans ,Inflammation ,Interleukin-6 ,Lipopolysaccharide Receptors ,Menopause ,Middle Aged ,Receptors ,Tumor Necrosis Factor ,Type I ,HIV ,immune activation ,inflammation ,menopause ,soluble CD14 ,soluble CD163 ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundPersistent immune activation due to gut barrier dysfunction is a suspected cause of morbidity in HIV, but the impact of menopause on this pathway is unknown.MethodsIn 350 women with HIV from the Women's Interagency HIV Study, plasma biomarkers of gut barrier dysfunction (intestinal fatty acid binding protein; IFAB), innate immune activation (soluble CD14 and CD163; sCD14, sCD163), and systemic inflammation (interleukin-6 and tumor necrosis factor receptor 1; IL-6, TNFR1) were measured at 674 person-visits spanning ≤2 years.ResultsMenopause (post- vs premenopausal status) was associated with higher plasma sCD14 and sCD163 in linear mixed-effects regression adjusting for age and other covariates (β = 161.89 ng/mL; 95% confidence interval [CI], 18.37-305.41 and 65.48 ng/mL, 95% CI, 6.64-124.33, respectively); but not with plasma IFAB, IL-6, or TNFR1. In piece-wise linear mixed-effects regression of biomarkers on years before/after the final menstrual period, sCD14 increased during the menopausal transition by 250.71 ng/mL per year (95% CI, 16.63-484.79; P = .04), but not in premenopausal or postmenopausal periods.ConclusionsIn women with HIV, menopause may increase innate immune activation, but data did not support an influence on the gut barrier or inflammation. Clinical implications of immune activation during menopausal transition warrant further investigation.
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- 2022
23. Whole genome sequence analysis of blood lipid levels in >66,000 individuals
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Selvaraj, Margaret Sunitha, Li, Xihao, Li, Zilin, Pampana, Akhil, Zhang, David Y, Park, Joseph, Aslibekyan, Stella, Bis, Joshua C, Brody, Jennifer A, Cade, Brian E, Chuang, Lee-Ming, Chung, Ren-Hua, Curran, Joanne E, de las Fuentes, Lisa, de Vries, Paul S, Duggirala, Ravindranath, Freedman, Barry I, Graff, Mariaelisa, Guo, Xiuqing, Heard-Costa, Nancy, Hidalgo, Bertha, Hwu, Chii-Min, Irvin, Marguerite R, Kelly, Tanika N, Kral, Brian G, Lange, Leslie, Li, Xiaohui, Lisa, Martin, Lubitz, Steven A, Manichaikul, Ani W, Michael, Preuss, Montasser, May E, Morrison, Alanna C, Naseri, Take, O’Connell, Jeffrey R, Palmer, Nicholette D, Peyser, Patricia A, Reupena, Muagututia S, Smith, Jennifer A, Sun, Xiao, Taylor, Kent D, Tracy, Russell P, Tsai, Michael Y, Wang, Zhe, Wang, Yuxuan, Bao, Wei, Wilkins, John T, Yanek, Lisa R, Zhao, Wei, Arnett, Donna K, Blangero, John, Boerwinkle, Eric, Bowden, Donald W, Chen, Yii-Der Ida, Correa, Adolfo, Cupples, L Adrienne, Dutcher, Susan K, Ellinor, Patrick T, Fornage, Myriam, Gabriel, Stacey, Germer, Soren, Gibbs, Richard, He, Jiang, Kaplan, Robert C, Kardia, Sharon LR, Kim, Ryan, Kooperberg, Charles, Loos, Ruth JF, Viaud-Martinez, Karine A, Mathias, Rasika A, McGarvey, Stephen T, Mitchell, Braxton D, Nickerson, Deborah, North, Kari E, Psaty, Bruce M, Redline, Susan, Reiner, Alexander P, Vasan, Ramachandran S, Rich, Stephen S, Willer, Cristen, Rotter, Jerome I, Rader, Daniel J, Lin, Xihong, Peloso, Gina M, and Natarajan, Pradeep
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Biological Sciences ,Biomedical and Clinical Sciences ,Genetics ,Epidemiology ,Health Sciences ,Biotechnology ,Heart Disease - Coronary Heart Disease ,Cardiovascular ,Heart Disease ,Human Genome ,Aetiology ,2.1 Biological and endogenous factors ,Good Health and Well Being ,Alleles ,Cholesterol ,LDL ,Genome-Wide Association Study ,Humans ,Lipids ,Whole Genome Sequencing ,NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium - Abstract
Blood lipids are heritable modifiable causal factors for coronary artery disease. Despite well-described monogenic and polygenic bases of dyslipidemia, limitations remain in discovery of lipid-associated alleles using whole genome sequencing (WGS), partly due to limited sample sizes, ancestral diversity, and interpretation of clinical significance. Among 66,329 ancestrally diverse (56% non-European) participants, we associate 428M variants from deep-coverage WGS with lipid levels; ~400M variants were not assessed in prior lipids genetic analyses. We find multiple lipid-related genes strongly associated with blood lipids through analysis of common and rare coding variants. We discover several associated rare non-coding variants, largely at Mendelian lipid genes. Notably, we observe rare LDLR intronic variants associated with markedly increased LDL-C, similar to rare LDLR exonic variants. In conclusion, we conducted a systematic whole genome scan for blood lipids expanding the alleles linked to lipids for multiple ancestries and characterize a clinically-relevant rare non-coding variant model for lipids.
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- 2022
24. Whole genome sequencing identifies structural variants contributing to hematologic traits in the NHLBI TOPMed program
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Wheeler, Marsha M, Stilp, Adrienne M, Rao, Shuquan, Halldórsson, Bjarni V, Beyter, Doruk, Wen, Jia, Mihkaylova, Anna V, McHugh, Caitlin P, Lane, John, Jiang, Min-Zhi, Raffield, Laura M, Jun, Goo, Sedlazeck, Fritz J, Metcalf, Ginger, Yao, Yao, Bis, Joshua B, Chami, Nathalie, de Vries, Paul S, Desai, Pinkal, Floyd, James S, Gao, Yan, Kammers, Kai, Kim, Wonji, Moon, Jee-Young, Ratan, Aakrosh, Yanek, Lisa R, Almasy, Laura, Becker, Lewis C, Blangero, John, Cho, Michael H, Curran, Joanne E, Fornage, Myriam, Kaplan, Robert C, Lewis, Joshua P, Loos, Ruth JF, Mitchell, Braxton D, Morrison, Alanna C, Preuss, Michael, Psaty, Bruce M, Rich, Stephen S, Rotter, Jerome I, Tang, Hua, Tracy, Russell P, Boerwinkle, Eric, Abecasis, Goncalo R, Blackwell, Thomas W, Smith, Albert V, Johnson, Andrew D, Mathias, Rasika A, Nickerson, Deborah A, Conomos, Matthew P, Li, Yun, Þorsteinsdóttir, Unnur, Magnússon, Magnús K, Stefansson, Kari, Pankratz, Nathan D, Bauer, Daniel E, Auer, Paul L, and Reiner, Alex P
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Epidemiology ,Biological Sciences ,Health Sciences ,Genetics ,Hematology ,Human Genome ,Aetiology ,2.1 Biological and endogenous factors ,Cardiovascular ,Good Health and Well Being ,Humans ,Genome-Wide Association Study ,Whole Genome Sequencing ,Blood Cells - Abstract
Genome-wide association studies have identified thousands of single nucleotide variants and small indels that contribute to variation in hematologic traits. While structural variants are known to cause rare blood or hematopoietic disorders, the genome-wide contribution of structural variants to quantitative blood cell trait variation is unknown. Here we utilized whole genome sequencing data in ancestrally diverse participants of the NHLBI Trans Omics for Precision Medicine program (N = 50,675) to detect structural variants associated with hematologic traits. Using single variant tests, we assessed the association of common and rare structural variants with red cell-, white cell-, and platelet-related quantitative traits and observed 21 independent signals (12 common and 9 rare) reaching genome-wide significance. The majority of these associations (N = 18) replicated in independent datasets. In genome-editing experiments, we provide evidence that a deletion associated with lower monocyte counts leads to disruption of an S1PR3 monocyte enhancer and decreased S1PR3 expression.
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- 2022
25. Body Fat Distribution, Cardiometabolic Traits, and Risk of Major Lower-Extremity Arterial Disease in Postmenopausal Women.
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Chen, Guo-Chong, Arthur, Rhonda, Kamensky, Victor, Chai, Jin Choul, Yu, Bing, Shadyab, Aladdin H, Allison, Matthew, Sun, Yangbo, Saquib, Nazmus, Wild, Robert A, Bao, Wei, Dannenberg, Andrew J, Rohan, Thomas E, Kaplan, Robert C, Wassertheil-Smoller, Sylvia, and Qi, Qibin
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Diabetes ,Clinical Research ,Aging ,Cardiovascular ,Patient Safety ,Nutrition ,Prevention ,Metabolic and endocrine ,Body Fat Distribution ,Body Mass Index ,Cardiovascular Diseases ,Extremities ,Female ,Humans ,Postmenopause ,Risk Factors - Abstract
ObjectiveTo assess the relationship between body fat distribution and incident lower-extremity arterial disease (LEAD).Research design and methodsWe included 155,925 postmenopausal women with anthropometric measures from the Women's Health Initiative who had no known LEAD at recruitment. A subset of 10,894 participants had body composition data quantified by DXA. Incident cases of symptomatic LEAD were ascertained and adjudicated through medical record review.ResultsWe identified 1,152 incident cases of LEAD during a median 18.8 years follow-up. After multivariable adjustment and mutual adjustment, waist and hip circumferences were positively and inversely associated with risk of LEAD, respectively (both P-trend < 0.0001). In a subset (n = 22,561) where various cardiometabolic biomarkers were quantified, a similar positive association of waist circumference with risk of LEAD was eliminated after adjustment for diabetes and HOMA of insulin resistance (P-trend = 0.89), whereas hip circumference remained inversely associated with the risk after adjustment for major cardiometabolic traits (P-trend = 0.0031). In the DXA subset, higher trunk fat (P-trend = 0.0081) and higher leg fat (P-trend < 0.0001) were associated with higher and lower risk of LEAD, respectively. Further adjustment for diabetes, dyslipidemia, and blood pressure diminished the association for trunk fat (P-trend = 0.49), yet the inverse association for leg fat persisted (P-trend = 0.0082).ConclusionsAmong U.S. postmenopausal women, a positive association of upper-body fat with risk of LEAD appeared to be attributable to traditional risk factors, especially insulin resistance. Lower-body fat was inversely associated with risk of LEAD beyond known risk factors.
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- 2022
26. Author Correction: Combined protein and transcript single-cell RNA sequencing in human peripheral blood mononuclear cells
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Vallejo, Jenifer, Saigusa, Ryosuke, Gulati, Rishab, Suthahar, Sujit Silas Armstrong, Suryawanshi, Vasantika, Alimadadi, Ahmad, Durant, Christopher P, Ghosheh, Yanal, Roy, Payel, Ehinger, Erik, Pattarabanjird, Tanyaporn, Hanna, David B, Landay, Alan L, Tracy, Russell P, Lazar, Jason M, Mack, Wendy J, Weber, Kathleen M, Adimora, Adaora A, Hodis, Howard N, Tien, Phyllis C, Ofotokun, Igho, Heath, Sonya L, Shemesh, Avishai, McNamara, Coleen A, Lanier, Lewis L, Hedrick, Catherine C, Kaplan, Robert C, and Ley, Klaus
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Biological Sciences ,Bioinformatics and Computational Biology ,Developmental Biology ,Biological sciences - Abstract
The original article [1] contained significant errors in Fig 1A which necessitated correction; the figure has since been updated to the corrected version.
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- 2022
27. Combined protein and transcript single-cell RNA sequencing in human peripheral blood mononuclear cells
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Vallejo, Jenifer, Saigusa, Ryosuke, Gulati, Rishab, Armstrong Suthahar, Sujit Silas, Suryawanshi, Vasantika, Alimadadi, Ahmad, Durant, Christopher P, Ghosheh, Yanal, Roy, Payel, Ehinger, Erik, Pattarabanjird, Tanyaporn, Hanna, David B, Landay, Alan L, Tracy, Russell P, Lazar, Jason M, Mack, Wendy J, Weber, Kathleen M, Adimora, Adaora A, Hodis, Howard N, Tien, Phyllis C, Ofotokun, Igho, Heath, Sonya L, Shemesh, Avishai, McNamara, Coleen A, Lanier, Lewis L, Hedrick, Catherine C, Kaplan, Robert C, and Ley, Klaus
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Biological Sciences ,Bioinformatics and Computational Biology ,HIV/AIDS ,Genetics ,Clinical Research ,Human Genome ,2.1 Biological and endogenous factors ,Aetiology ,Good Health and Well Being ,Female ,Flow Cytometry ,Gene Expression Profiling ,HIV Infections ,Humans ,Leukocytes ,Mononuclear ,Sequence Analysis ,RNA ,Single-Cell Analysis ,Transcriptome ,CVD ,HIV ,scRNA-seq ,Transcriptomes ,Antibodies ,Human ,Developmental Biology ,Biological sciences - Abstract
BackgroundCryopreserved peripheral blood mononuclear cells (PBMCs) are frequently collected and provide disease- and treatment-relevant data in clinical studies. Here, we developed combined protein (40 antibodies) and transcript single-cell (sc)RNA sequencing (scRNA-seq) in PBMCs.ResultsAmong 31 participants in the Women's Interagency HIV Study (WIHS), we sequenced 41,611 cells. Using Boolean gating followed by Seurat UMAPs (tool for visualizing high-dimensional data) and Louvain clustering, we identified 50 subsets among CD4+ T, CD8+ T, B, NK cells, and monocytes. This resolution was superior to flow cytometry, mass cytometry, or scRNA-seq without antibodies. Combined protein and transcript scRNA-seq allowed for the assessment of disease-related changes in transcriptomes and cell type proportions. As a proof-of-concept, we showed such differences between healthy and matched individuals living with HIV with and without cardiovascular disease.ConclusionsIn conclusion, combined protein and transcript scRNA sequencing is a suitable and powerful method for clinical investigations using PBMCs.
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- 2022
28. A multi-ethnic polygenic risk score is associated with hypertension prevalence and progression throughout adulthood
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Kurniansyah, Nuzulul, Goodman, Matthew O, Kelly, Tanika N, Elfassy, Tali, Wiggins, Kerri L, Bis, Joshua C, Guo, Xiuqing, Palmas, Walter, Taylor, Kent D, Lin, Henry J, Haessler, Jeffrey, Gao, Yan, Shimbo, Daichi, Smith, Jennifer A, Yu, Bing, Feofanova, Elena V, Smit, Roelof AJ, Wang, Zhe, Hwang, Shih-Jen, Liu, Simin, Wassertheil-Smoller, Sylvia, Manson, JoAnn E, Lloyd-Jones, Donald M, Rich, Stephen S, Loos, Ruth JF, Redline, Susan, Correa, Adolfo, Kooperberg, Charles, Fornage, Myriam, Kaplan, Robert C, Psaty, Bruce M, Rotter, Jerome I, Arnett, Donna K, Morrison, Alanna C, Franceschini, Nora, Levy, Daniel, and Sofer, Tamar
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Epidemiology ,Biological Sciences ,Health Sciences ,Genetics ,Hypertension ,Human Genome ,Prevention ,Cardiovascular ,Aging ,Aetiology ,2.1 Biological and endogenous factors ,Adult ,Diabetes Mellitus ,Type 2 ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Humans ,Multifactorial Inheritance ,Prevalence ,Risk Factors ,NHLBI Trans-Omics in Precision Medicine (TOPMed) Consortium - Abstract
In a multi-stage analysis of 52,436 individuals aged 17-90 across diverse cohorts and biobanks, we train, test, and evaluate a polygenic risk score (PRS) for hypertension risk and progression. The PRS is trained using genome-wide association studies (GWAS) for systolic, diastolic blood pressure, and hypertension, respectively. For each trait, PRS is selected by optimizing the coefficient of variation (CV) across estimated effect sizes from multiple potential PRS using the same GWAS, after which the 3 trait-specific PRSs are combined via an unweighted sum called "PRSsum", forming the HTN-PRS. The HTN-PRS is associated with both prevalent and incident hypertension at 4-6 years of follow up. This association is further confirmed in age-stratified analysis. In an independent biobank of 40,201 individuals, the HTN-PRS is confirmed to be predictive of increased risk for coronary artery disease, ischemic stroke, type 2 diabetes, and chronic kidney disease.
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- 2022
29. Whole-genome association analyses of sleep-disordered breathing phenotypes in the NHLBI TOPMed program
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Cade, Brian E, Lee, Jiwon, Sofer, Tamar, Wang, Heming, Zhang, Man, Chen, Han, Gharib, Sina A, Gottlieb, Daniel J, Guo, Xiuqing, Lane, Jacqueline M, Liang, Jingjing, Lin, Xihong, Mei, Hao, Patel, Sanjay R, Purcell, Shaun M, Saxena, Richa, Shah, Neomi A, Evans, Daniel S, Hanis, Craig L, Hillman, David R, Mukherjee, Sutapa, Palmer, Lyle J, Stone, Katie L, Tranah, Gregory J, Abecasis, Gonçalo R, Boerwinkle, Eric A, Correa, Adolfo, Cupples, L Adrienne, Kaplan, Robert C, Nickerson, Deborah A, North, Kari E, Psaty, Bruce M, Rotter, Jerome I, Rich, Stephen S, Tracy, Russell P, Vasan, Ramachandran S, Wilson, James G, Zhu, Xiaofeng, and Redline, Susan
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Biological Sciences ,Genetics ,Sleep Research ,Dental/Oral and Craniofacial Disease ,Lung ,Human Genome ,2.1 Biological and endogenous factors ,Aetiology ,Good Health and Well Being ,Alleles ,Chromatin Immunoprecipitation Sequencing ,Female ,Gene Expression Regulation ,Genetic Association Studies ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Genotype ,Humans ,Male ,National Heart ,Lung ,and Blood Institute (U.S.) ,Phenotype ,Precision Medicine ,Research ,Signal Transduction ,Sleep Apnea Syndromes ,United States ,Whole Genome Sequencing ,Sleep-disordered breathing ,Sleep apnea ,Whole-genome sequencing ,WGS ,Genome-wide association study ,GWAS ,NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium ,TOPMed Sleep Working Group ,Clinical Sciences - Abstract
BackgroundSleep-disordered breathing is a common disorder associated with significant morbidity. The genetic architecture of sleep-disordered breathing remains poorly understood. Through the NHLBI Trans-Omics for Precision Medicine (TOPMed) program, we performed the first whole-genome sequence analysis of sleep-disordered breathing.MethodsThe study sample was comprised of 7988 individuals of diverse ancestry. Common-variant and pathway analyses included an additional 13,257 individuals. We examined five complementary traits describing different aspects of sleep-disordered breathing: the apnea-hypopnea index, average oxyhemoglobin desaturation per event, average and minimum oxyhemoglobin saturation across the sleep episode, and the percentage of sleep with oxyhemoglobin saturation
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- 2021
30. Microbial co-occurrence complicates associations of gut microbiome with US immigration, dietary intake and obesity
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Wang, Zheng, Usyk, Mykhaylo, Vázquez-Baeza, Yoshiki, Chen, Guo-Chong, Isasi, Carmen R, Williams-Nguyen, Jessica S, Hua, Simin, McDonald, Daniel, Thyagarajan, Bharat, Daviglus, Martha L, Cai, Jianwen, North, Kari E, Wang, Tao, Knight, Rob, Burk, Robert D, Kaplan, Robert C, and Qi, Qibin
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Nutrition ,Obesity ,Cardiovascular ,Oral and gastrointestinal ,Acculturation ,Adult ,Aged ,Aged ,80 and over ,Bacteria ,Cohort Studies ,Diet ,Eating ,Emigrants and Immigrants ,Emigration and Immigration ,Feces ,Female ,Gastrointestinal Microbiome ,Hispanic or Latino ,Humans ,Male ,Metagenomics ,Middle Aged ,RNA ,Ribosomal ,16S ,United States ,Microbiome ,Hispanic population ,Environmental Sciences ,Biological Sciences ,Information and Computing Sciences ,Bioinformatics - Abstract
BackgroundObesity and related comorbidities are major health concerns among many US immigrant populations. Emerging evidence suggests a potential involvement of the gut microbiome. Here, we evaluated gut microbiome features and their associations with immigration, dietary intake, and obesity in 2640 individuals from a population-based study of US Hispanics/Latinos.ResultsThe fecal shotgun metagenomics data indicate that greater US exposure is associated with reduced ɑ-diversity, reduced functions of fiber degradation, and alterations in individual taxa, potentially related to a westernized diet. However, a majority of gut bacterial genera show paradoxical associations, being reduced with US exposure and increased with fiber intake, but increased with obesity. The observed paradoxical associations are not explained by host characteristics or variation in bacterial species but might be related to potential microbial co-occurrence, as seen by positive correlations among Roseburia, Prevotella, Dorea, and Coprococcus. In the conditional analysis with mutual adjustment, including all genera associated with both obesity and US exposure in the same model, the positive associations of Roseburia and Prevotella with obesity did not persist, suggesting that their positive associations with obesity might be due to their co-occurrence and correlations with obesity-related taxa, such as Dorea and Coprococcus.ConclusionsAmong US Hispanics/Latinos, US exposure is associated with unfavorable gut microbiome profiles for obesity risk, potentially related to westernized diet during acculturation. Microbial co-occurrence could be an important factor to consider in future studies relating individual gut microbiome taxa to environmental factors and host health and disease.
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- 2021
31. Investigation of the Interplay between Circulating Lipids and IGF-I and Relevance to Breast Cancer Risk: An Observational and Mendelian Randomization Study
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Tan, Vanessa Y, Bull, Caroline J, Biernacka, Kalina M, Teumer, Alexander, Richardson, Tom G, Sanderson, Eleanor, Corbin, Laura J, Dudding, Tom, Qi, Qibin, Kaplan, Robert C, Rotter, Jerome I, Friedrich, Nele, Völker, Uwe, Mayerle, Julia, Perks, Claire M, Holly, Jeff MP, and Timpson, Nicholas J
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Health Services and Systems ,Biomedical and Clinical Sciences ,Health Sciences ,Oncology and Carcinogenesis ,Clinical Research ,Breast Cancer ,Cardiovascular ,Atherosclerosis ,Cancer ,Prevention ,2.1 Biological and endogenous factors ,Aetiology ,Breast Neoplasms ,Causality ,Cholesterol ,HDL ,Cholesterol ,LDL ,Cross-Sectional Studies ,Female ,Genome-Wide Association Study ,Humans ,Insulin-Like Growth Factor I ,Mendelian Randomization Analysis ,Triglycerides ,Medical and Health Sciences ,Epidemiology ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundCirculating lipids and insulin-like growth factor 1 (IGF-I) have been reliably associated with breast cancer. Observational studies suggest an interplay between lipids and IGF-I, however, whether these relationships are causal and if pathways from these phenotypes to breast cancer overlap is unclear.MethodsMendelian randomization (MR) was conducted to estimate the relationship between lipids or IGF-I and breast cancer risk using genetic summary statistics for lipids (low-density lipoprotein cholesterol, LDL-C; high-density lipoprotein cholesterol, HDL-C; triglycerides, TGs), IGF-I and breast cancer from GLGC/UKBB (N = 239,119), CHARGE/UKBB (N = 252,547), and Breast Cancer Association Consortium (N = 247,173), respectively. Cross-sectional observational and MR analyses were conducted to assess the bi-directional relationship between lipids and IGF-I in SHIP (N = 3,812) and UKBB (N = 422,389), and using genetic summary statistics from GLGC (N = 188,577) and CHARGE/UKBB (N = 469,872).ResultsIn multivariable MR (MVMR) analyses, the OR for breast cancer per 1-SD increase in HDL-C and TG was 1.08 [95% confidence interval (CI), 1.04-1.13] and 0.94 (95% CI, 0.89-0.98), respectively. The OR for breast cancer per 1-SD increase in IGF-I was 1.09 (95% CI, 1.04-1.15). MR analyses suggested a bi-directional TG-IGF-I relationship (TG-IGF-I β per 1-SD: -0.13; 95% CI, -0.23 to -0.04; and IGF-I-TG β per 1-SD: -0.11; 95% CI, -0.18 to -0.05). There was little evidence for a causal relationship between HDL-C and LDL-C with IGF-I. In MVMR analyses, associations of TG or IGF-I with breast cancer were robust to adjustment for IGF-I or TG, respectively.ConclusionsOur findings suggest a causal role of HDL-C, TG, and IGF-I in breast cancer. Observational and MR analyses support an interplay between IGF-I and TG; however, MVMR estimates suggest that TG and IGF-I may act independently to influence breast cancer.ImpactOur findings should be considered in the development of prevention strategies for breast cancer, where interventions are known to modify circulating lipids and IGF-I.
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- 2021
32. Circulating Metabolites Associated With Steatotic Liver Disease and Liver Enzymes: A Multiplatform Population-Based Study
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Abozaid, Yasir J., Ayada, Ibrahim, van Kleef, Laurens A., Goulding, Neil J., Williams-Nguyen, Jessica S., Kaplan, Robert C., de Knegt, Robert J., Wagenknecht, Lynne E., Allred, Nicholette D., Timpson, Nicholas J., Norris, Jill M., Ida Chen, Yii-Der, Ikram, M. Arfan, Brouwer, Willem Pieter, and Ghanbari, Mohsen
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- 2024
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33. Prevalence of electronic cigarette use and its determinants in us persons of Hispanic/Latino background: The Hispanic community health study / study of Latinos (HCHS/SOL)
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April-Sanders, Ayana K., Daviglus, Martha L., Lee, Un Jung, Perreira, Krista M., Kaplan, Robert C., Blaha, Michael J, Pirzada, Amber, Giachello, Aida L., Bhatnagar, Aruni, Robertson, Rose Marie, Vu, Thanh-Huyen T., and Rodriguez, Carlos J.
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- 2023
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34. Tryptophan metabolism, gut microbiota, and carotid artery plaque in women with and without HIV infection
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Luo, Kai, Wang, Zheng, Peters, Brandilyn A., Hanna, David B., Wang, Tao, Sollecito, Christopher C., Grassi, Evan, Wiek, Fanua, Peter, Lauren St, Usyk, Mykhaylo, Post, Wendy S., Landay, Alan L., Hodis, Howard N., Weber, Kathleen M., French, Audrey, Golub, Elizabeth T., Lazar, Jason, Gustafson, Deborah, Sharma, Anjali, Anastos, Kathryn, Clish, Clary B., Knight, Rob, Kaplan, Robert C., Burk, Robert D., and Qi, Qibin
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- 2023
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35. Consent for Use of Genetic Data among US Hispanics/Latinos : Results from the Hispanic Community Health Study/Study of Latinos
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Gonzalez, Sara, Strizich, Garrett, Isasi, Carmen R., Hua, Simin, Comas, Betsy, Sofer, Tamar, Thyagarajan, Bharat, Perreira, Krista M., Talavera, Gregory A., Daviglus, Martha L., Nelson, Sarah C., Giachello, Aida L., Schneiderman, Neil, and Kaplan, Robert C.
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- 2021
36. Physical Activity, Cardiovascular Status, Mortality, and Prediabetes in Hispanic and Non-Hispanic Adults
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Alver, Sarah K., primary, Pan, Stephanie, additional, Mossavar-Rahmani, Yasmin, additional, Sotres-Alvarez, Daniela, additional, Evenson, Kelly R., additional, Floyd, James S., additional, Xanthakis, Vanessa, additional, Lin, Juan, additional, Cuthbertson, Carmen, additional, Gallo, Linda C., additional, Cai, Jianwen, additional, Penedo, Frank J., additional, Llabre, Maria M., additional, Matsushita, Kunihiro, additional, Talavera, Gregory A., additional, Pirzada, Amber, additional, Spartano, Nicole, additional, Daviglus, Martha L., additional, Vasan, Ramachandran S., additional, and Kaplan, Robert C., additional
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- 2024
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37. Gut microbiota, blood metabolites, and left ventricular diastolic dysfunction in US Hispanics/Latinos
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Luo, Kai, primary, Taryn, Alkis, additional, Moon, Eun-Hye, additional, Peters, Brandilyn A., additional, Solomon, Scott D., additional, Daviglus, Martha L., additional, Kansal, Mayank M., additional, Thyagarajan, Bharat, additional, Gellman, Marc D., additional, Cai, Jianwen, additional, Burk, Robert D., additional, Knight, Rob, additional, Kaplan, Robert C., additional, Cheng, Susan, additional, Rodriguez, Carlos J., additional, Qi, Qibin, additional, and Yu, Bing, additional
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- 2024
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38. Healthful eating patterns, serum metabolite profile and risk of diabetes in a population-based prospective study of US Hispanics/Latinos
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Chen, Guo-Chong, Chai, Jin Choul, Xing, Jiaqian, Moon, Jee-Young, Shan, Zhilei, Yu, Bing, Mossavar-Rahman, Yasmin, Sotres-Alvarez, Daniela, Li, Jun, Mattei, Josiemer, Daviglus, Martha L., Perkins, David L., Burk, Robert D., Boerwinkle, Eric, Kaplan, Robert C., Hu, Frank B., and Qi, Qibin
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- 2022
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39. Predictors of incident diabetes in two populations: framingham heart study and hispanic community health study / study of latinos
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Kaplan, Robert C., Song, Rebecca J., Lin, Juan, Xanthakis, Vanessa, Hua, Simin, Chernofsky, Ariel, Evenson, Kelly R., Walker, Maura E., Cuthbertson, Carmen, Murabito, Joanne M., Cordero, Christina, Daviglus, Martha, Perreira, Krista M., Gellman, Marc, Sotres-Alvarez, Daniela, Vasan, Ramachandran S., Xue, Xiaonan, Spartano, Nicole L., and Mossavar-Rahmani, Yasmin
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- 2022
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40. LifeCourse Socioeconomic Position and Ideal Cardiovascular Health in Hispanic/Latino Adults of the Hispanic Community Health Study/Study of Latinos.
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Filigrana, Paola, Jee-Young Moon, Gallo, Linda C., Fernández-Rhodes, Lindsay, Perreira, Krista M., Daviglus, Martha L., Thyagarajan, Bharat, Garcia-Bedoya, Olga L., Jianwen Cai, Xiaonan Xue, Kaplan, Robert C., Suglia, Shakira, and Isasi, Carmen R.
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- 2024
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41. Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices
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Natarajan, Pradeep, Pampana, Akhil, Graham, Sarah E., Ruotsalainen, Sanni E., Perry, James A., de Vries, Paul S., Broome, Jai G., Pirruccello, James P., Honigberg, Michael C., Aragam, Krishna, Wolford, Brooke, Brody, Jennifer A., Antonacci-Fulton, Lucinda, Arden, Moscati, Aslibekyan, Stella, Assimes, Themistocles L., Ballantyne, Christie M., Bielak, Lawrence F., Bis, Joshua C., Cade, Brian E., Do, Ron, Doddapaneni, Harsha, Emery, Leslie S., Hung, Yi-Jen, Irvin, Marguerite R., Khan, Alyna T., Lange, Leslie, Lee, Jiwon, Lemaitre, Rozenn N., Martin, Lisa W., Metcalf, Ginger, Montasser, May E., Moon, Jee-Young, Muzny, Donna, O’Connell, Jeffrey R., Palmer, Nicholette D., Peralta, Juan M., Peyser, Patricia A., Stilp, Adrienne M., Tsai, Michael, Wang, Fei Fei, Weeks, Daniel E., Yanek, Lisa R., Wilson, James G., Abecasis, Goncalo, Arnett, Donna K., Becker, Lewis C., Blangero, John, Boerwinkle, Eric, Bowden, Donald W., Chang, Yi-Cheng, Chen, Yii-Der I., Choi, Won Jung, Correa, Adolfo, Curran, Joanne E., Daly, Mark J., Dutcher, Susan K., Ellinor, Patrick T., Fornage, Myriam, Freedman, Barry I., Gabriel, Stacey, Germer, Soren, Gibbs, Richard A., He, Jiang, Hveem, Kristian, Jarvik, Gail P., Kaplan, Robert C., Kardia, Sharon L. R., Kenny, Eimear, Kim, Ryan W., Kooperberg, Charles, Laurie, Cathy C., Lee, Seonwook, Lloyd-Jones, Don M., Loos, Ruth J. F., Lubitz, Steven A., Mathias, Rasika A., Martinez, Karine A. Viaud, McGarvey, Stephen T., Mitchell, Braxton D., Nickerson, Deborah A., North, Kari E., Palotie, Aarno, Park, Cheol Joo, Psaty, Bruce M., Rao, D. C., Redline, Susan, Reiner, Alexander P., Seo, Daekwan, Seo, Jeong-Sun, Smith, Albert V., Tracy, Russell P., Vasan, Ramachandran S., Kathiresan, Sekar, Cupples, L. Adrienne, Rotter, Jerome I., Morrison, Alanna C., Rich, Stephen S., Ripatti, Samuli, Willer, Cristen, and Peloso, Gina M.
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- 2021
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42. Associations of Helicobacter pylori and hepatitis A seropositivity with asthma in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL): addressing the hygiene hypothesis
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Alvarez, Christian S., Avilés-Santa, M. Larissa, Freedman, Neal D., Perreira, Krista M., Garcia-Bedoya, Olga, Kaplan, Robert C., Daviglus, Martha L., Graubard, Barry I., Talavera, Gregory A., Thyagarajan, Bharat, and Camargo, M. Constanza
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- 2021
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43. Impact of Amerind ancestry and FADS genetic variation on omega-3 deficiency and cardiometabolic traits in Hispanic populations
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Yang, Chaojie, Hallmark, Brian, Chai, Jin Choul, O’Connor, Timothy D., Reynolds, Lindsay M., Wood, Alexis C., Seeds, Michael, Chen, Yii-Der Ida, Steffen, Lyn M., Tsai, Michael Y., Kaplan, Robert C., Daviglus, Martha L., Mandarino, Lawrence J., Fretts, Amanda M., Lemaitre, Rozenn N., Coletta, Dawn K., Blomquist, Sarah A., Johnstone, Laurel M., Tontsch, Chandra, Qi, Qibin, Ruczinski, Ingo, Rich, Stephen S., Mathias, Rasika A., Chilton, Floyd H., and Manichaikul, Ani
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- 2021
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44. Metabolic and inflammatory perturbation of diabetes associated gut dysbiosis in people living with and without HIV infection.
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Luo, Kai, Peters, Brandilyn A., Moon, Jee-Young, Xue, Xiaonan, Wang, Zheng, Usyk, Mykhaylo, Hanna, David B., Landay, Alan L., Schneider, Michael F., Gustafson, Deborah, Weber, Kathleen M., French, Audrey, Sharma, Anjali, Anastos, Kathryn, Wang, Tao, Brown, Todd, Clish, Clary B., Kaplan, Robert C., Knight, Rob, and Burk, Robert D.
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HIV infections ,DIABETES ,DYSBIOSIS - Abstract
Background: Gut dysbiosis has been linked with both HIV infection and diabetes, but its interplay with metabolic and inflammatory responses in diabetes, particularly in the context of HIV infection, remains unclear. Methods: We first conducted a cross-sectional association analysis to characterize the gut microbial, circulating metabolite, and immune/inflammatory protein features associated with diabetes in up to 493 women (~ 146 with prevalent diabetes with 69.9% HIV +) of the Women's Interagency HIV Study. Prospective analyses were then conducted to determine associations of identified metabolites with incident diabetes over 12 years of follow-up in 694 participants (391 women from WIHS and 303 men from the Multicenter AIDS Cohort Study; 166 incident cases were recorded) with and without HIV infection. Mediation analyses were conducted to explore whether gut bacteria–diabetes associations are explained by altered metabolites and proteins. Results: Seven gut bacterial genera were identified to be associated with diabetes (FDR-q < 0.1), with positive associations for Shigella, Escherichia, Megasphaera, and Lactobacillus, and inverse associations for Adlercreutzia, Ruminococcus, and Intestinibacter. Importantly, the associations of most species, especially Adlercreutzia and Ruminococcus, were largely independent of antidiabetic medications use. Meanwhile, 18 proteins and 76 metabolites, including 3 microbially derived metabolites (trimethylamine N-oxide, phenylacetylglutamine (PAGln), imidazolepropionic acid (IMP)), 50 lipids (e.g., diradylglycerols (DGs) and triradylglycerols (TGs)) and 23 non-lipid metabolites, were associated with diabetes (FDR-q < 0.1), with the majority showing positive associations and more than half of them (59/76) associated with incident diabetes. In mediation analyses, several proteins, especially interleukin-18 receptor 1 and osteoprotegerin, IMP and PAGln partially mediate the observed bacterial genera–diabetes associations, particularly for those of Adlercreutzia and Escherichia. Many diabetes-associated metabolites and proteins were altered in HIV, but no effect modification on their associations with diabetes was observed by HIV. Conclusion: Among individuals with and without HIV, multiple gut bacterial genera, blood metabolites, and proinflammatory proteins were associated with diabetes. The observed mediated effects by metabolites and proteins in genera–diabetes associations highlighted the potential involvement of inflammatory and metabolic perturbations in the link between gut dysbiosis and diabetes in the context of HIV infection. [ABSTRACT FROM AUTHOR]
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- 2024
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45. Risk Factors for Sudden Cardiac Arrest Among Hispanic or Latino Adults in Southern California: Ventura PRESTO and HCHS/SOL
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Reinier, Kyndaron, primary, Moon, Jee‐Young, additional, Chugh, Harpriya S., additional, Sargsyan, Arayik, additional, Nakamura, Kotoka, additional, Norby, Faye L., additional, Uy‐Evanado, Audrey, additional, Talavera, Gregory A., additional, Gallo, Linda C., additional, Daviglus, Martha L., additional, Hadduck, Katy, additional, Shepherd, Daniel, additional, Salvucci, Angelo, additional, Kaplan, Robert C., additional, and Chugh, Sumeet S., additional
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- 2023
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46. Rare variants in long non-coding RNAs are associated with blood lipid levels in the TOPMed whole-genome sequencing study
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Wang, Yuxuan, primary, Selvaraj, Margaret Sunitha, additional, Li, Xihao, additional, Li, Zilin, additional, Holdcraft, Jacob A., additional, Arnett, Donna K., additional, Bis, Joshua C., additional, Blangero, John, additional, Boerwinkle, Eric, additional, Bowden, Donald W., additional, Cade, Brian E., additional, Carlson, Jenna C., additional, Carson, April P., additional, Chen, Yii-Der Ida, additional, Curran, Joanne E., additional, de Vries, Paul S., additional, Dutcher, Susan K., additional, Ellinor, Patrick T., additional, Floyd, James S., additional, Fornage, Myriam, additional, Freedman, Barry I., additional, Gabriel, Stacey, additional, Germer, Soren, additional, Gibbs, Richard A., additional, Guo, Xiuqing, additional, He, Jiang, additional, Heard-Costa, Nancy, additional, Hildalgo, Bertha, additional, Hou, Lifang, additional, Irvin, Marguerite R., additional, Joehanes, Roby, additional, Kaplan, Robert C., additional, Kardia, Sharon LR., additional, Kelly, Tanika N., additional, Kim, Ryan, additional, Kooperberg, Charles, additional, Kral, Brian G., additional, Levy, Daniel, additional, Li, Changwei, additional, Liu, Chunyu, additional, Lloyd-Jone, Don, additional, Loos, Ruth JF., additional, Mahaney, Michael C., additional, Martin, Lisa W., additional, Mathias, Rasika A., additional, Minster, Ryan L., additional, Mitchell, Braxton D., additional, Montasser, May E., additional, Morrison, Alanna C., additional, Murabito, Joanne M., additional, Naseri, Take, additional, O'Connell, Jeffrey R., additional, Palmer, Nicholette D., additional, Preuss, Michael H., additional, Psaty, Bruce M., additional, Raffield, Laura M., additional, Rao, Dabeeru C., additional, Redline, Susan, additional, Reiner, Alexander P., additional, Rich, Stephen S., additional, Ruepena, Muagututi’a Sefuiva, additional, Sheu, Wayne H.-H., additional, Smith, Jennifer A., additional, Smith, Albert, additional, Tiwari, Hemant K., additional, Tsai, Michael Y., additional, Viaud-Martinez, Karine A., additional, Wang, Zhe, additional, Yanek, Lisa R., additional, Zhao, Wei, additional, Rotter, Jerome I., additional, Lin, Xihong, additional, Natarajan, Pradeep, additional, and Peloso, Gina M., additional
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- 2023
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47. Sex hormones, the stool microbiome, and subclinical atherosclerosis in women with and without HIV
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Peters, Brandilyn A, primary, Hanna, David B, additional, Wang, Yi, additional, Weber, Kathleen M, additional, Topper, Elizabeth, additional, Appleton, Allison A, additional, Sharma, Anjali, additional, Hodis, Howard N, additional, Santoro, Nanette, additional, Guillemette, Chantal, additional, Caron, Patrick, additional, Knight, Rob, additional, Burk, Robert D, additional, Kaplan, Robert C, additional, and Qi, Qibin, additional
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- 2023
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48. HIV infection and cardiovascular disease have both shared and distinct monocyte gene expression features: Women’s Interagency HIV study
- Author
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Lin, Juan, primary, Ehinger, Erik, additional, Hanna, David B., additional, Qi, Qibin, additional, Wang, Tao, additional, Ghosheh, Yanal, additional, Mueller, Karin, additional, Anastos, Kathryn, additional, Lazar, Jason M., additional, Mack, Wendy J., additional, Tien, Phyllis C., additional, Berman, Joan W., additional, Cohen, Mardge H., additional, Ofotokun, Igho, additional, Gange, Stephen, additional, Liu, Chenglong, additional, Heath, Sonya L., additional, Tracy, Russell P., additional, Hodis, Howard N., additional, Landay, Alan L., additional, Ley, Klaus, additional, and Kaplan, Robert C., additional
- Published
- 2023
- Full Text
- View/download PDF
49. Identification of Dietary Supplements Associated with Blood Metabolites in the Hispanic Community Health Study/Study of Latinos Cohort Study
- Author
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Kaplan, Robert C., primary, Williams-Nguyen, Jessica S., additional, Huang, Yuhan, additional, Mossavar-Rahmani, Yasmin, additional, Yu, Bing, additional, Boerwinkle, Eric, additional, Gellman, Marc D., additional, Daviglus, Martha, additional, Chilcoat, Aisha, additional, Van Horn, Linda, additional, Faurot, Kim, additional, Qi, Qibin, additional, and Greenlee, Heather, additional
- Published
- 2023
- Full Text
- View/download PDF
50. Nutritional blood concentration biomarkers in the Hispanic Community Health Study/Study of Latinos: Measurement characteristics and power
- Author
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Boe, Lillian A, primary, Mossavar-Rahmani, Yasmin, additional, Sotres-Alvarez, Daniela, additional, Daviglus, Martha L, additional, Durazo-Arvizu, Ramon A, additional, Thyagarajan, Bharat, additional, Kaplan, Robert C, additional, and Shaw, Pamela A, additional
- Published
- 2023
- Full Text
- View/download PDF
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