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Article ; Online: Race/Ethnicity and Clinical Prediction Algorithms for Childhood Asthma.

Witonsky, Jonathan / Burchard, Esteban González

NEJM evidence

2023 Volume 2, Issue 10, Page(s) EVIDe2300187

Abstract: In 1985, the United States Department of Health and Human Services released the Report of the Secretary's Task Force on Black & Minority Health. ...

Abstract	In 1985, the United States Department of Health and Human Services released the Report of the Secretary's Task Force on Black & Minority Health.
MeSH term(s)	Humans ; Child ; Ethnicity ; Racial Groups ; Asthma
Language	English
Publishing date	2023-09-26
Publishing country	United States
Document type	Editorial
ISSN	2766-5526
ISSN (online)	2766-5526
DOI	10.1056/EVIDe2300187
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Article ; Online: Need for Racial and Ethnic Diversity in Asthma Precision Medicine.

González Burchard, Esteban / Borrell, Luisa N

The New England journal of medicine

2021 Volume 385, Issue 24, Page(s) 2297–2298

MeSH term(s)	Asthma/drug therapy ; Ethnicity ; Humans ; Precision Medicine ; Racial Groups
Language	English
Publishing date	2021-12-08
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMe2114944
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Article: Phenotypic subtyping via contrastive learning.

Gorla, Aditya / Sankararaman, Sriram / Burchard, Esteban / Flint, Jonathan / Zaitlen, Noah / Rahmani, Elior

bioRxiv : the preprint server for biology

2023

Abstract: Defining and accounting for subphenotypic structure has the potential to increase statistical power and provide a deeper understanding of the heterogeneity in the molecular basis of complex disease. Existing phenotype subtyping methods primarily rely on ... ...

Abstract	Defining and accounting for subphenotypic structure has the potential to increase statistical power and provide a deeper understanding of the heterogeneity in the molecular basis of complex disease. Existing phenotype subtyping methods primarily rely on clinically observed heterogeneity or metadata clustering. However, they generally tend to capture the dominant sources of variation in the data, which often originate from variation that is not descriptive of the mechanistic heterogeneity of the phenotype of interest; in fact, such dominant sources of variation, such as population structure or technical variation, are, in general, expected to be independent of subphenotypic structure. We instead aim to find a subspace with signal that is unique to a group of samples for which we believe that subphenotypic variation exists (e.g., cases of a disease). To that end, we introduce Phenotype Aware Components Analysis (PACA), a contrastive learning approach leveraging canonical correlation analysis to robustly capture weak sources of subphenotypic variation. In the context of disease, PACA learns a gradient of variation unique to cases in a given dataset, while leveraging control samples for accounting for variation and imbalances of biological and technical confounders between cases and controls. We evaluated PACA using an extensive simulation study, as well as on various subtyping tasks using genotypes, transcriptomics, and DNA methylation data. Our results provide multiple strong evidence that PACA allows us to robustly capture weak unknown variation of interest while being calibrated and well-powered, far superseding the performance of alternative methods. This renders PACA as a state-of-the-art tool for defining
Language	English
Publishing date	2023-01-06
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.01.05.522921
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Article ; Online: Medical research: Missing patients.

Burchard, Esteban G

Nature

2014 Volume 513, Issue 7518, Page(s) 301–302

MeSH term(s)	Adolescent ; African Americans/genetics ; African Americans/statistics & numerical data ; Asthma/mortality ; Biomedical Research/methods ; Clinical Trials as Topic/ethics ; Clinical Trials as Topic/standards ; Continental Population Groups/genetics ; Continental Population Groups/statistics & numerical data ; Gene-Environment Interaction ; Humans ; Male ; Minority Groups/statistics & numerical data ; Patient Selection/ethics ; Workforce
Language	English
Publishing date	2014-09-18
Publishing country	England
Document type	Journal Article
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/513301a
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Article ; Online: Atopic dermatitis, race, and genetics.

Kumar, Rajesh / Seibold, Max A / Burchard, Esteban G

The Journal of allergy and clinical immunology

2019 Volume 145, Issue 1, Page(s) 108–110

MeSH term(s)	African Americans ; Dermatitis, Atopic ; Eczema ; Humans
Language	English
Publishing date	2019-11-15
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	121011-7
ISSN	1097-6825 ; 1085-8725 ; 0091-6749
ISSN (online)	1097-6825 ; 1085-8725
ISSN	0091-6749
DOI	10.1016/j.jaci.2019.11.008
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Article ; Online: Genetic Ancestry to Improve Precision of Race/Ethnicity-based Lung Function Equations in Children.

Witonsky, Jonathan / Elhawary, Jennifer R / Eng, Celeste / Rodríguez-Santana, José R / Borrell, Luisa N / Burchard, Esteban G

American journal of respiratory and critical care medicine

2022 Volume 205, Issue 6, Page(s) 725–727

MeSH term(s)	African Americans/genetics ; Child ; Ethnicity ; Humans ; Lung ; Respiratory Physiological Phenomena ; Whites/genetics
Language	English
Publishing date	2022-01-24
Publishing country	United States
Document type	Letter ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1180953-x
ISSN	1535-4970 ; 0003-0805 ; 1073-449X
ISSN (online)	1535-4970
ISSN	0003-0805 ; 1073-449X
DOI	10.1164/rccm.202109-2088LE
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Article ; Online: Race- and Ethnicity-Based Spirometry Reference Equations: Are They Accurate for Genetically Admixed Children?

Witonsky, Jonathan / Elhawary, Jennifer R / Eng, Celeste / Rodríguez-Santana, José R / Borrell, Luisa N / Burchard, Esteban G

Chest

2022 Volume 162, Issue 1, Page(s) 184–195

Abstract: Background: Variation in genetic ancestry among genetically admixed racial and ethnic groups may influence the fit of guideline-recommended spirometry reference equations, which rely on self-identified race and ethnicity.: Research question: What is ... ...

Abstract	Background: Variation in genetic ancestry among genetically admixed racial and ethnic groups may influence the fit of guideline-recommended spirometry reference equations, which rely on self-identified race and ethnicity. Research question: What is the influence of genetic ancestry on the fit of race- and ethnicity-based spirometry reference equations in populations of genetically admixed children? Study design and methods: Cross-sectional fit of guideline-recommended race- and ethnicity-based spirometry reference equations was evaluated in healthy control participants from case-control studies of asthma. Anthropometry, blood samples, and spirometric measurements were obtained for 599 genetically admixed children 8 to 21 years of age. Genetic ancestry was estimated using genome-wide genotype data. Equation fit, measured as a mean z score, was assessed in self-identified African American (n = 275) and Puerto Rican (n = 324) children as well as genetic ancestry-defined strata of each population. Results: For African American children, African American-derived equations fit for predicting FEV Interpretation: Guideline-recommended spirometry reference equations yielded biased estimates of lung function in genetically admixed children with high variation of African ancestry. Spirometry could benefit from reference equations that incorporate genetic ancestry, either for more precise application of the current equations or the derivation and use of new equations.
MeSH term(s)	Child ; Cross-Sectional Studies ; Ethnicity/genetics ; Forced Expiratory Volume ; Humans ; Reference Values ; Spirometry ; Vital Capacity
Language	English
Publishing date	2022-01-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1032552-9
ISSN	1931-3543 ; 0012-3692
ISSN (online)	1931-3543
ISSN	0012-3692
DOI	10.1016/j.chest.2021.12.664
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Article ; Online: Office of Management and Budget Racial/Ethnic Categories in Mortality Research: A Framework for Including the Voices of Racialized Communities.

Hayes-Bautista, David E / Bryant, Mara / Yudell, Michael / Hayes-Bautista, Teodocia Maria / Partlow, Keosha / Popejoy, Alice Beecher / Burchard, Esteban / Hsu, Paul

American journal of public health

2021 Volume 111, Issue S2, Page(s) S133–S140

Abstract: Since its founding, the US government has sorted people into racial/ethnic categories for the purpose of allowing or disallowing their access to social services and protections. The current Office of Management and Budget racial/ethnic categories ... ...

Abstract	Since its founding, the US government has sorted people into racial/ethnic categories for the purpose of allowing or disallowing their access to social services and protections. The current Office of Management and Budget racial/ethnic categories originated in a dominant racial narrative that assumed a binary biological difference between Whites and non-Whites, with a hard-edged separation between them. There is debate about their continued use in researching group differences in mortality profiles and health outcomes: should we use them with modifications, cease using them entirely, or develop a new epistemology of human similarities and differences? This essay offers a research framework for including in these debates the daily lived experiences of the 110 million racialized non-White Americans whose lived experiences are the legacy of historically limited access to society's services and protections. The experience of Latinos in California is used to illustrate the major elements of this framework that may have an effect on mortality and health outcomes: a subaltern fuzzy-edged multivalent racial narrative, agency, voice, and community and cultural resilience.
MeSH term(s)	Adult ; Black or African American/statistics & numerical data ; Aged ; Aged, 80 and over ; Ethnicity/statistics & numerical data ; Female ; Health Status Disparities ; Hispanic or Latino/statistics & numerical data ; Humans ; Male ; Middle Aged ; Mortality/ethnology ; Race Factors/statistics & numerical data ; Social Class ; United States ; White People/statistics & numerical data
Language	English
Publishing date	2021-07-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	121100-6
ISSN	1541-0048 ; 0090-0036 ; 0002-9572
ISSN (online)	1541-0048
ISSN	0090-0036 ; 0002-9572
DOI	10.2105/AJPH.2021.306361
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Article ; Online: Disentangling the impact of alcohol use and hepatitis C on insulin action in Latino individuals.

Kim, Rebecca G / Kramer-Feldman, Jonathan / Bacchetti, Peter / Grimes, Barbara / Burchard, Esteban / Eng, Celeste / Hu, Donglei / Hellerstein, Marc / Khalili, Mandana

Alcoholism, clinical and experimental research

2021 Volume 46, Issue 1, Page(s) 87–99

Abstract: Background: Alcohol, insulin resistance (IR), and hepatitis C (HCV) are all significant contributors to adverse outcomes of chronic liver disease. Latinos are disproportionately affected by these risk factors. We investigated the relationship between ... ...

Abstract	Background: Alcohol, insulin resistance (IR), and hepatitis C (HCV) are all significant contributors to adverse outcomes of chronic liver disease. Latinos are disproportionately affected by these risk factors. We investigated the relationship between alcohol use and insulin action in a prospective cohort of Latino individuals with and without HCV. Methods: One hundred fifty-three nondiabetic Latino individuals (60 HCV+, 93 HCV-) underwent clinical evaluation and metabolic testing; 56 had repeat testing over a median follow-up of 1.5 years. Peripheral IR and hepatic IR were measured via steady-state plasma glucose (SSPG) and endogenous glucose production during a two-step, 240-min insulin suppression test. Insulin secretion (IS) was measured using the graded glucose infusion test. Alcohol use was categorized as none, moderate (≤1 drink/day for women and ≤2 drinks/day for men), and heavy (>moderate). Multivariable models including HCV status assessed associations of alcohol use with baseline SSPG, hepatic IR and IS, and changes in these parameters over time. Results: Overall, the median age was 44 years, 63.4% were male, 66.7% overweight/ obese, and 31.9% had heavy lifetime alcohol use while 60.4% had moderate lifetime alcohol use. SSPG and IS were similar by levels of alcohol use at baseline and alcohol use was not statistically significantly associated with change in these measures over time. However, lifetime daily heavy alcohol use (vs. not heavy, coef 2.4 μU-mg/kg-min-ml, p = 0.04) and HCV status (coef 4.4 μU-mg/kg-min-ml, p = 0.0003) were independently associated with higher baseline hepatic IR, and current heavy alcohol use was associated with greater change in hepatic IR in follow-up (coef 5.8 μU-mg/kg-min-ml, p = 0.03). Conclusions: In this cohort of Latino individuals, lifetime and current heavy alcohol use influenced hepatic IR and its change over time. Strategies to decrease rates of heavy alcohol use or increase abstinence along with lifestyle modification and anti-HCV therapy to reduce metabolic risk are critical to prevent adverse liver and metabolic outcomes in Latino individuals.
MeSH term(s)	Adult ; Alcohol Drinking/adverse effects ; Cohort Studies ; Cytochrome P-450 CYP2E1/genetics ; Ethanol/administration & dosage ; Female ; Genotype ; Hepatitis C/complications ; Hepatitis C/physiopathology ; Hispanic or Latino/statistics & numerical data ; Humans ; Insulin/pharmacology ; Insulin Resistance/ethnology ; Insulin Secretion/physiology ; Liver/drug effects ; Liver/physiopathology ; Liver Diseases/epidemiology ; Male ; Middle Aged ; Prospective Studies
Chemical Substances	Insulin ; Ethanol (3K9958V90M) ; Cytochrome P-450 CYP2E1 (EC 1.14.13.-)
Language	English
Publishing date	2021-11-23
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	428999-7
ISSN	1530-0277 ; 0145-6008
ISSN (online)	1530-0277
ISSN	0145-6008
DOI	10.1111/acer.14743
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Article ; Online: A noncoding regulatory variant in IKZF1 increases acute lymphoblastic leukemia risk in Hispanic/Latino children.

de Smith, Adam J / Wahlster, Lara / Jeon, Soyoung / Kachuri, Linda / Black, Susan / Langie, Jalen / Cato, Liam D / Nakatsuka, Nathan / Chan, Tsz-Fung / Xia, Guangze / Mazumder, Soumyaa / Yang, Wenjian / Gazal, Steven / Eng, Celeste / Hu, Donglei / Burchard, Esteban González / Ziv, Elad / Metayer, Catherine / Mancuso, Nicholas /

Yang, Jun J / Ma, Xiaomei / Wiemels, Joseph L / Yu, Fulong / Chiang, Charleston W K / Sankaran, Vijay G

Cell genomics

2024 Volume 4, Issue 4, Page(s) 100526

Abstract: Hispanic/Latino children have the highest risk of acute lymphoblastic leukemia (ALL) in the US compared to other racial/ethnic groups, yet the basis of this remains incompletely understood. Through genetic fine-mapping analyses, we identified a new ... ...

Abstract	Hispanic/Latino children have the highest risk of acute lymphoblastic leukemia (ALL) in the US compared to other racial/ethnic groups, yet the basis of this remains incompletely understood. Through genetic fine-mapping analyses, we identified a new independent childhood ALL risk signal near IKZF1 in self-reported Hispanic/Latino individuals, but not in non-Hispanic White individuals, with an effect size of ∼1.44 (95% confidence interval = 1.33-1.55) and a risk allele frequency of ∼18% in Hispanic/Latino populations and <0.5% in European populations. This risk allele was positively associated with Indigenous American ancestry, showed evidence of selection in human history, and was associated with reduced IKZF1 expression. We identified a putative causal variant in a downstream enhancer that is most active in pro-B cells and interacts with the IKZF1 promoter. This variant disrupts IKZF1 autoregulation at this enhancer and results in reduced enhancer activity in B cell progenitors. Our study reveals a genetic basis for the increased ALL risk in Hispanic/Latino children.
MeSH term(s)	Humans ; Child ; Genetic Predisposition to Disease/genetics ; Polymorphism, Single Nucleotide ; Transcription Factors/genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics ; Hispanic or Latino/genetics ; Ikaros Transcription Factor/genetics
Chemical Substances	Transcription Factors ; IKZF1 protein, human ; Ikaros Transcription Factor (148971-36-2)
Language	English
Publishing date	2024-03-26
Publishing country	United States
Document type	Journal Article
ISSN	2666-979X
ISSN (online)	2666-979X
DOI	10.1016/j.xgen.2024.100526
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