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Article ; Online: Genome-Wide Causation Studies of Complex Diseases.

Jiao, Rong / Chen, Xiangning / Boerwinkle, Eric / Xiong, Momiao

Journal of computational biology : a journal of computational molecular cell biology

2022 Volume 29, Issue 8, Page(s) 908–931

Abstract: Despite significant progress in dissecting the genetic architecture of complex diseases by genome-wide association studies (GWAS), the signals identified by association analysis may not have specific pathological relevance to diseases so that a large ... ...

Abstract	Despite significant progress in dissecting the genetic architecture of complex diseases by genome-wide association studies (GWAS), the signals identified by association analysis may not have specific pathological relevance to diseases so that a large fraction of disease-causing genetic variants is still hidden. Association is used to measure dependence between two variables or two sets of variables. GWAS test association between a disease and single-nucleotide polymorphisms (SNPs) (or other genetic variants) across the genome. Association analysis may detect superficial patterns between disease and genetic variants. Association signals provide limited information on the causal mechanism of diseases. The use of association analysis as a major analytical platform for genetic studies of complex diseases is a key issue that may hamper discovery of disease mechanisms, calling into the questions the ability of GWAS to identify loci-underlying diseases. It is time to move beyond association analysis toward techniques, which enables the discovery of the underlying causal genetic structures of complex diseases. To achieve this, we propose the concept of genome-wide causation studies (GWCS) as an alternative to GWAS and develop additive noise models (ANMs) for genetic causation analysis. Type 1 error rates and power of the ANMs in testing causation are presented. We conducted GWCS of schizophrenia. Both simulation and real data analysis show that the proportion of the overlapped association and causation signals is small. Thus, we anticipate that our analysis will stimulate serious discussion of the applicability of GWAS and GWCS.
MeSH term(s)	Computer Simulation ; Genome ; Genome-Wide Association Study/methods ; Humans ; Linkage Disequilibrium ; Polymorphism, Single Nucleotide ; Schizophrenia/genetics
Language	English
Publishing date	2022-04-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	2030900-4
ISSN	1557-8666 ; 1066-5277
ISSN (online)	1557-8666
ISSN	1066-5277
DOI	10.1089/cmb.2021.0676
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Article: Epigenome-wide association study of incident type 2 diabetes in Black and White participants from the Atherosclerosis Risk in Communities Study.

Venkataraghavan, Sowmya / Pankow, James S / Boerwinkle, Eric / Fornage, Myriam / Selvin, Elizabeth / Ray, Debashree

medRxiv : the preprint server for health sciences

2023

Abstract: DNA methylation studies of incident type 2 diabetes in US populations are limited, and to our knowledge none included individuals of African descent living in the US. We performed an epigenome-wide association analysis of blood-based methylation levels ... ...

Abstract	DNA methylation studies of incident type 2 diabetes in US populations are limited, and to our knowledge none included individuals of African descent living in the US. We performed an epigenome-wide association analysis of blood-based methylation levels at CpG sites with incident type 2 diabetes using Cox regression in 2,091 Black and 1,029 White individuals from the Atherosclerosis Risk in Communities study. At an epigenome-wide significance threshold of 10
Language	English
Publishing date	2023-08-13
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.08.09.23293896
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Article ; Online: Equilibrium points and their stability of COVID-19 in US.

Hu, Xiaoxi / Hu, Zixin / Xu, Tao / Zhang, Kai / Lu, Henry H / Zhao, Jinying / Boerwinkle, Eric / Jin, Li / Xiong, Momiao

Scientific reports

2024 Volume 14, Issue 1, Page(s) 1628

Abstract: This study aims to develop an advanced mathematic model and investigate when and how will the COVID-19 in the US be evolved to endemic. We employed a nonlinear ordinary differential equations-based model to simulate COVID-19 transmission dynamics, ... ...

Abstract	This study aims to develop an advanced mathematic model and investigate when and how will the COVID-19 in the US be evolved to endemic. We employed a nonlinear ordinary differential equations-based model to simulate COVID-19 transmission dynamics, factoring in vaccination efforts. Multi-stability analysis was performed on daily new infection data from January 12, 2021 to December 12, 2022 across 50 states in the US. Key indices such as eigenvalues and the basic reproduction number were utilized to evaluate stability and investigate how the pandemic COVD-19 will evolve to endemic in the US. The transmissional, recovery, vaccination rates, vaccination effectiveness, eigenvalues and reproduction numbers ([Formula: see text] and [Formula: see text]) in the endemic equilibrium point were estimated. The stability attractor regions for these parameters were identified and ranked. Our multi-stability analysis revealed that while the endemic equilibrium points in the 50 states remain unstable, there is a significant trend towards stable endemicity in the US. The study's stability analysis, coupled with observed epidemiological waves in the US, suggested that the COVID-19 pandemic may not conclude with the virus's eradication. Nevertheless, the virus is gradually becoming endemic. Effectively strategizing vaccine distribution is pivotal for this transition.
MeSH term(s)	Humans ; COVID-19/epidemiology ; Pandemics/prevention & control ; Models, Theoretical ; Nonlinear Dynamics
Language	English
Publishing date	2024-01-18
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-51729-w
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Article ; Online: Prozone masks elevated SARS-CoV-2 antibody level measurements.

Sandoval, Micaela N / McClellan, Samuel P / Pont, Stephen J / Ross, Jessica A / Swartz, Michael D / Silberman, Mark A / Boerwinkle, Eric

PloS one

2024 Volume 19, Issue 3, Page(s) e0301232

Abstract: We report a prozone effect in measurement of SARS-CoV-2 spike protein antibody levels from an antibody surveillance program. Briefly, the prozone effect occurs in immunoassays when excessively high antibody concentration disrupts the immune complex ... ...

Abstract	We report a prozone effect in measurement of SARS-CoV-2 spike protein antibody levels from an antibody surveillance program. Briefly, the prozone effect occurs in immunoassays when excessively high antibody concentration disrupts the immune complex formation, resulting in a spuriously low reported result. Following participant inquiries, we observed anomalously low measurement of SARS-CoV-2 spike protein antibody levels using the Roche Elecsys® Anti-SARS-CoV-2 S immunoassay from participants in the Texas Coronavirus Antibody Research survey (Texas CARES), an ongoing prospective, longitudinal antibody surveillance program. In July, 2022, samples were collected from ten participants with anomalously low results for serial dilution studies, and a prozone effect was confirmed. From October, 2022 to March, 2023, serial dilution of samples detected 74 additional cases of prozone out of 1,720 participants' samples. Prozone effect may affect clinical management of at-risk populations repeatedly exposed to SARS-CoV-2 spike protein through multiple immunizations or serial infections, making awareness and mitigation of this issue paramount.
MeSH term(s)	Humans ; SARS-CoV-2 ; COVID-19 ; Masks ; Prospective Studies ; Immunoassay/methods ; Antibodies, Viral ; Spike Glycoprotein, Coronavirus
Chemical Substances	spike protein, SARS-CoV-2 ; Antibodies, Viral ; Spike Glycoprotein, Coronavirus
Language	English
Publishing date	2024-03-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0301232
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Article ; Online: Association Between Emergency Medical Service Agency Intubation Rate and Intubation Success.

Thomas, Jordan / Crowe, Remle / Schulz, Kevin / Wang, Henry E / De Oliveira Otto, Marcia C / Karfunkle, Bejamin / Boerwinkle, Eric / Huebinger, Ryan

Annals of emergency medicine

2024

Abstract: Study objective: Airway management is a crucial part of out-of-hospital care. It is not known if the rate of overall agency intubation attempts is associated with intubation success. We sought to evaluate the association between agency intubation ... ...

Abstract	Study objective: Airway management is a crucial part of out-of-hospital care. It is not known if the rate of overall agency intubation attempts is associated with intubation success. We sought to evaluate the association between agency intubation attempt rate and intubation success using a national out-of-hospital database. Methods: We conducted a retrospective secondary analysis of the ESO Data Collaborative from 2018 to 2019, and included all adult cases with an endotracheal intubation attempt. We calculated the number of intubations attempted per 100 responses, advanced life support responses, and transports for each agency. We excluded cases originating at health care facilities and outliers. We used multivariable logistic regression to evaluate the association between agency intubation attempt rate and 1) intubation success and 2) first-pass success. We adjusted for confounders. Results: We included 1,005 agencies attempting 58,509 intubations. Overall, the intubation success rate was 78.8%, and the first-pass success rate was 68.5%. Per agency, the median rate of intubation attempts per 100 emergency medical service responses was 0.8 (interquartile range 0.6 to 1.1). Rates of intubation attempts per 100 responses (adjusted odds ratio [aOR] 1.7; 95% confidence interval [CI] 1.6 to 1.8), advanced life support responses (aOR 1.18; 95% CI 1.16 to 1.20), and transports (aOR 1.21; 95% CI 1.18 to 1.22) were all associated with intubation success. These relationships were similar for first-pass success but with smaller effect sizes. Conclusion: Higher agency rates of intubation attempts were associated with increased rates of intubation success and first-pass success.
Language	English
Publishing date	2024-01-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	603080-4
ISSN	1097-6760 ; 0196-0644
ISSN (online)	1097-6760
ISSN	0196-0644
DOI	10.1016/j.annemergmed.2023.11.005
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Zs.A 1344: Show issues

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Article ; Online: Social determinants of health predict readmission following COVID-19 hospitalization: a health information exchange-based retrospective cohort study.

Sandoval, Micaela N / Mikhail, Jennifer L / Fink, Melyssa K / Tortolero, Guillermo A / Cao, Tru / Ramphul, Ryan / Husain, Junaid / Boerwinkle, Eric

Frontiers in public health

2024 Volume 12, Page(s) 1352240

Abstract: Introduction: Since February 2020, over 104 million people in the United States have been diagnosed with SARS-CoV-2 infection, or COVID-19, with over 8.5 million reported in the state of Texas. This study analyzed social determinants of health as ... ...

Abstract	Introduction: Since February 2020, over 104 million people in the United States have been diagnosed with SARS-CoV-2 infection, or COVID-19, with over 8.5 million reported in the state of Texas. This study analyzed social determinants of health as predictors for readmission among COVID-19 patients in Southeast Texas, United States. Methods: A retrospective cohort study was conducted investigating demographic and clinical risk factors for 30, 60, and 90-day readmission outcomes among adult patients with a COVID-19-associated inpatient hospitalization encounter within a regional health information exchange between February 1, 2020, to December 1, 2022. Results and discussion: In this cohort of 91,007 adult patients with a COVID-19-associated hospitalization, over 21% were readmitted to the hospital within 90 days (
MeSH term(s)	Adult ; Humans ; United States ; COVID-19/epidemiology ; Patient Readmission ; Retrospective Studies ; Health Information Exchange ; Social Determinants of Health ; SARS-CoV-2 ; Hospitalization
Language	English
Publishing date	2024-03-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2711781-9
ISSN	2296-2565 ; 2296-2565
ISSN (online)	2296-2565
ISSN	2296-2565
DOI	10.3389/fpubh.2024.1352240
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Article ; Online: Translational genomics is not a spectator sport: a call to action.

Boerwinkle, Eric

Genetic epidemiology

2012 Volume 36, Issue 2, Page(s) 85–87

MeSH term(s)	Cohort Studies ; Genome, Human ; Genomics/methods ; Genomics/trends ; Humans ; Politics ; Research Design ; Research Support as Topic ; Translational Medical Research/methods ; Translational Medical Research/trends ; United States
Language	English
Publishing date	2012-02
Publishing country	United States
Document type	Editorial
ZDB-ID	605785-8
ISSN	1098-2272 ; 0741-0395
ISSN (online)	1098-2272
ISSN	0741-0395
DOI	10.1002/gepi.21607
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Article ; Online: Metabolomics of Dietary Intake of Total, Animal, and Plant Protein: Results from the Atherosclerosis Risk in Communities (ARIC) Study.

Bernard, Lauren / Chen, Jingsha / Kim, Hyunju / Wong, Kari E / Steffen, Lyn M / Yu, Bing / Boerwinkle, Eric / Rebholz, Casey M

Current developments in nutrition

2023 Volume 7, Issue 4, Page(s) 100067

Abstract: Background: Dietary consumption has traditionally been studied through food intake questionnaires. Metabolomics can be used to identify blood markers of dietary protein that may complement existing dietary assessment tools.: Objectives: We aimed to ... ...

Abstract	Background: Dietary consumption has traditionally been studied through food intake questionnaires. Metabolomics can be used to identify blood markers of dietary protein that may complement existing dietary assessment tools. Objectives: We aimed to identify associations between 3 dietary protein sources (total protein, animal protein, and plant protein) and serum metabolites using data from the Atherosclerosis Risk in Communities Study. Methods: Participants' dietary protein intake was derived from a food frequency questionnaire administered by an interviewer, and fasting serum samples were collected at study visit 1 (1987-1989). Untargeted metabolomic profiling was performed in 2 subgroups (subgroup 1: Results: In this study of 3914 middle-aged adults, the mean (SD) age was 54 (6) y, 60% were women, and 61% were Black. We identified 41 metabolites significantly associated with dietary protein intake. Twenty-six metabolite associations overlapped between total protein and animal protein, such as pyroglutamine, creatine, 3-methylhistidine, and 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid. Plant protein was uniquely associated with 11 metabolites, such as tryptophan betaine, 4-vinylphenol sulfate, Conclusions: The results of 17 of the 41 metabolites (41%) were consistent with those of previous nutritional metabolomic studies and specific protein-rich food items. We discovered 24 metabolites that had not been previously associated with dietary protein intake. These results enhance the validity of candidate markers of dietary protein intake and introduce novel metabolomic markers of dietary protein intake.
Language	English
Publishing date	2023-03-24
Publishing country	United States
Document type	Journal Article
ISSN	2475-2991
ISSN (online)	2475-2991
DOI	10.1016/j.cdnut.2023.100067
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Article ; Online: Metabolomic Markers of Ultra-Processed Food and Incident CKD.

Su, Donghan / Chen, Jingsha / Du, Shutong / Kim, Hyunju / Yu, Bing / Wong, Kari E / Boerwinkle, Eric / Rebholz, Casey M

Clinical journal of the American Society of Nephrology : CJASN

2023 Volume 18, Issue 3, Page(s) 327–336

Abstract: Background: High ultra-processed food consumption is associated with higher risk of CKD. However, there is no biomarker for ultra-processed food, and the mechanism through which ultra-processed food is associated with CKD is not clear. Metabolomics can ... ...

Abstract	Background: High ultra-processed food consumption is associated with higher risk of CKD. However, there is no biomarker for ultra-processed food, and the mechanism through which ultra-processed food is associated with CKD is not clear. Metabolomics can provide objective biomarkers of ultra-processed food and provide important insights into the mechanisms by which ultra-processed food is associated with risk of incident CKD. Our objective was to identify serum metabolites associated with ultra-processed food consumption and investigate whether ultra-processed food-associated metabolites are prospectively associated with incident CKD. Methods: We used data from 3751 Black and White men and women (aged 45-64 years) in the Atherosclerosis Risk in Communities study. Dietary intake was assessed using a semiquantitative 66-item food frequency questionnaire, and ultra-processed food was classified using the NOVA classification system. Multivariable linear regression models were used to identify the association between 359 metabolites and ultra-processed food consumption. Cox proportional hazards models were used to investigate the prospective association of ultra-processed food-associated metabolites with incident CKD. Results: Twelve metabolites (saccharine, homostachydrine, stachydrine, N2, N2-dimethylguanosine, catechol sulfate, caffeine, 3-methyl-2-oxovalerate, theobromine, docosahexaenoate, glucose, mannose, and bradykinin) were significantly associated with ultra-processed food consumption after controlling for false discovery rate <0.05 and adjusting for sociodemographic factors, health behaviors, eGFR, and total energy intake. The 12 ultra-processed food-related metabolites significantly improved the prediction of ultra-processed food consumption (difference in C statistics: 0.069, P <1×10 -16 ). Higher levels of mannose, glucose, and N2, N2-dimethylguanosine were associated with higher risk of incident CKD after a median follow-up of 23 years. Conclusions: We identified 12 serum metabolites associated with ultra-processed food consumption and three of them were positively associated with incident CKD. Mannose and N2, N2-dimethylguanosine are novel markers of CKD that may explain observed associations between ultra-processed food and CKD. Podcast: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_03_08_CJN08480722.mp3.
MeSH term(s)	Male ; Humans ; Female ; Food, Processed ; Mannose ; Energy Intake ; Biomarkers ; Renal Insufficiency, Chronic/diagnosis ; Renal Insufficiency, Chronic/epidemiology ; Glucose ; Diet/adverse effects
Chemical Substances	Mannose (PHA4727WTP) ; Biomarkers ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2023-01-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2226665-3
ISSN	1555-905X ; 1555-9041
ISSN (online)	1555-905X
ISSN	1555-9041
DOI	10.2215/CJN.0000000000000062
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Zs.A 6584: Show issues

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Article ; Online: Agency factors associated with first response systems that improve out-of-hospital cardiac arrest outcomes.

Huebinger, Ryan / Spring, Mary / McNally, Brian / Humphries, Amanda / Persse, David / Diggs, Dominique / Boerwinkle, Eric / Bobrow, Bentley

Resuscitation

2023 Volume 193, Page(s) 109954

Abstract: Background: Data are conflicting regarding the association between first responder (FR) intervention and improved outcomes after out-of-hospital cardiac arrest (OHCA). We evaluated characteristics of agencies that have positive associations between FR ... ...

Abstract	Background: Data are conflicting regarding the association between first responder (FR) intervention and improved outcomes after out-of-hospital cardiac arrest (OHCA). We evaluated characteristics of agencies that have positive associations between FR interventions and outcomes. Methods: We analyzed the 2016-2021 national Cardiac Arrest Registry to Enhance Survival (CARES). We defined the exposures as FR CPR and AED. The outcome was survival with favorable neurologic status. We used logistic regression models to evaluate the association between FR interventions with OHCA outcome for each agency, stratifying agencies into positive association (95% confidence interval above 1) and no/inverse association (95% confidence below or including 1). We compared characteristics between cohorts. Results: For the association between FR CPR and outcomes, 21 agencies caring for 42,856 OHCAs had a positive association; 371 agencies caring for 449,824 OHCAs had no association. For FR AED, 47 agencies caring for 103,120 OHCAs had a positive association; 262 agencies caring for 327,761 OHCAs had no association. Comparing agency characteristics for FR CPR, agencies with a positive association had more annual OHCAs (+300), lower FR CPR rate (-11.3%), and lower FR AED rate (-10.8%). Comparing FR AED, agencies with a positive association had more OHCAs per year (+150.5), lower FR CPR rate (-6.8%), lower FR AED rate (-13.3%), lower response time (-0.6 minutes), and more OHCAs from high-income neighborhoods (+3.7%). Conclusion: FR AED more commonly had a positive association with outcomes than FR CPR. Agencies with better outcomes from FR interventions treated more OHCAs and had lower rates of FR intervention.
MeSH term(s)	Humans ; Cardiopulmonary Resuscitation ; Out-of-Hospital Cardiac Arrest/therapy ; Emergency Medical Services ; Registries ; Logistic Models
Language	English
Publishing date	2023-09-01
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	189901-6
ISSN	1873-1570 ; 0300-9572
ISSN (online)	1873-1570
ISSN	0300-9572
DOI	10.1016/j.resuscitation.2023.109954
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