Publications

Most important

  1. Gene expression in African Americans, Puerto Ricans and Mexican Americans reveals ancestry-specific patterns of genetic architecture.

    Kachuri L*, Mak ACY*, Hu D, Eng C, Huntsman S, Elhawary JR, Gupta N, Gabriel S, Xiao S, Keys KL, Oni-Orisan A, Rodríguez-Santana JR, LeNoir MA, Borrell LN, Zaitlen NA, Williams LK, Gignoux CR*, Burchard EG*, Ziv E*.

    Nat Genet. 2023 Jun; 55(6):952-96. PMID: 37231098. *Shared authors

    We leveraged RNA sequencing data to explore ancestry-related differences in the genetic architecture of whole-blood gene expression. Our analysis identified that the heritability, or the amount of variation due to genetics, of gene expression significantly increased with greater proportions of African genetic ancestry and decreased with higher proportions of Indigenous American ancestry. We also demonstrated that among heritable protein-coding genes, the prevalence of ancestry-specific expression quantitative trait loci (anc-eQTLs) was 30% in African ancestry and 8% for Indigenous American ancestry segments. These findings along with our novel admixed population-trained transcriptome prediction models highlight the importance of measuring gene expression across large and ancestrally diverse populations for enabling new discoveries and reducing disparities.

  2. Race and Genetic Ancestry in Medicine - A Time for Reckoning with Racism.

    Borrell LN*, Elhawary JR*, Fuentes-Afflick E, Witonsky J, Bhakta N, Wu AHB, Bibbins-Domingo K, Rodríguez-Santana JR, Lenoir MA, Gavin JR 3rd, Kittles RA, Zaitlen NA, Wilkes DS, Powe NR, Ziv E, Burchard EG*.

    N Engl J Med. 2021 Feb 4;384(5):474-480. PMID: 33406325. *Shared authors

    In the context of the national debate over the use of race/ethnicity in clinical medicine and biomedical research, some have recommended a race/ethnicity-blind approach to medicine. This recommendation is based on the premise that race and ethnicity, as social constructs, have no utility in medicine for clinical decisions and its use perpetuates racism and health inequities. We contend that race and ethnicity are social constructs that capture a wide array of social and cultural exposures. Thus, race and ethnicity represent the biological embodiment of these exposures, and therefore, affect health outcomes. Furthermore, we argue that because race/ethnicity is correlated with genetic ancestry, it may capture information about the likelihood of having genetic variants for many genes. These genetic variants may have clinical significance in medicine and biomedical research. We, therefore, reason that race and ethnicity are complex and multidimensional variables that capture information about discrimination, socioeconomic position, access to healthcare, environmental exposures, and genetic variation, all of which are important for clinical decisions and outcomes.

  3. Genetic ancestry influences asthma susceptibility and lung function among Latinos.

    Pino-Yanes M, Thakur N, Gignoux CR, Galanter JM, Roth LA, Eng C, Nishimura KK, Oh SS, Vora H, Huntsman S, Nguyen EA, Hu D, Drake KA, Conti DV, Moreno-Estrada A, Sandoval K, Winkler CA, Borrell LN, Lurmann F, Islam TS, Davis A, Farber HJ, Meade K, Avila PC, Serebrisky D, Bibbins-Domingo K, Lenoir MA, Ford JG, Brigino-Buenaventura E, Rodriguez-Cintron W, Thyne SM, Sen S, Rodriguez-Santana JR, Bustamante CD, Williams LK, Gilliland FD, Gauderman WJ, Kumar R, Torgerson DG, Burchard EG.

    J Allergy Clin Immunol. 2015 Jan. 135(1):228-3. PMID: 25301036.

    We demonstrated that genetic ancestry is associated with current clinical standards for pulmonary reference equations. The association with genetic ancestry makes routine pulmonary function measures clinically inaccurate for racially mixed populations such as African Americans and Latinos. It is well known that air pollution and socioeconomic status are also associated with race/ethnicity and therefore, by proxy, genetic ancestry. Herein, we used data from the largest gene-environment study of asthma in minority children to demonstrate that the association between genetic ancestry and lung function were largely driven by genetic factors rather than social or environmental factors.

  4. The genetics of Mexico recapitulates Native American substructure and affects biomedical traits.

    Moreno-Estrada A, Gignoux CR, Fernández-López JC, Zakharia F, Sikora M, Contreras AV, Acuña-Alonzo V, Sandoval K, Eng C, Romero-Hidalgo S, Ortiz-Tello P, Robles V, Kenny EE, Nuño-Arana I, Barquera-Lozano R, Macín-Pérez G, Granados-Arriola J, Huntsman S, Galanter JM, Via M, Ford JG, Chapela R, Rodriguez-Cintron W, Rodríguez-Santana JR, Romieu I, Sienra-Monge JJ, del Rio Navarro B, London SJ, Ruiz-Linares A, Garcia-Herrera R, Estrada K, Hidalgo-Miranda A, Jimenez-Sanchez G, Carnevale A, Soberón X, Canizales-Quinteros S, Rangel-Villalobos H, Silva-Zolezzi I, *Burchard EG and *Bustamante CD. Human genetics.

    Science. 2014 Jun 13; 344(6189):1280-5. PMID: 24926019. *Shared senior authors

    We furthered our NEJM 2010 results by demonstrating that sub-continental Native American ancestry also influences current clinical standards for pulmonary reference equations among Latino populations by as much as 10%. This work represents analysis of data from the largest study of Native Americans ever published. In doing so, we were able to illuminate the rich demographic history among indigenous populations in the Americas. Incorporating genetic ancestry into normative pulmonary predicative equations improves lung function estimates and more accurately categorize disease severity in Latino populations. Our results have allowed us to advance precision medicine for populations that are traditionally understudied.

  5. Early-life air pollution and asthma risk in minority children. The GALA II and SAGE II studies.

    Nishimura KK, Galanter JM, Roth LA, Oh SS, Thakur N, Nguyen EA, Thyne S, Farber HJ, Serebrisky D, Kumar R, Brigino-Buenaventura E, Davis A, LeNoir MA, Meade K, Rodriguez-Cintron W, Avila PC, Borrell LN, Bibbins-Domingo K, Rodriguez-Santana JR, Sen Ś, Lurmann F, Balmes JR, Burchard EG.

    Am J Respir Crit Care Med. 2013; 188(3):309-18. PMID: 23750510.

    Using the largest pediatric gene–environment study of asthma in Latinos and African Americans in the United States, we found that exposure during infancy to NO2, a traffic-related air pollutant, was associated with a 17% increased risk for subsequent development of childhood asthma. African American children were more susceptible than their non-African American neighbors. Our results suggest that air pollution may contribute to the higher prevalence of asthma, especially in some minority children exposed to higher levels of air pollution.

  6. Genetic ancestry and lung function predictions.

    Kumar R*, Seibold MA*, Aldrich MC*, Williams KL*, Reiner AP, Colangelo L, Galanter J, Gignoux C, Hu D, Sen S, Choudhry S, Peterson EL, Rodriguez-Santana J, Rodriguez-Cintron W, Nalls MA, Leak TS, O'Meara E, Meibohm B, Kritchevsky SB, Li R, Harris TB, Nickerson DA, Fornage M, Enright P, Ziv E, Smith LJ, Liu K, Burchard EG.

    N Engl J Med. 2010; 363(4):321-30. PMID: 20647190. *Shared authors

    We were the first to demonstrate that current pulmonary predictive equations, which rely on self-identified race/ethnicity alone, misdiagnose lung disease among African American subjects. We demonstrated that current clinical standards lead to pulmonary disease misclassification by as much as 15% error in African Americans. We then leveraged genetic ancestry, a proxy for race/ethnicity, to improve accuracy in the diagnosis of lung disease for African American patients. This likely applies to other racial groups and disease classifications as well. Incorporating genetic ancestry into normative equations improves lung function estimates and more accurately categorize disease severity.

 

2021 to today

2011 to 2020

2001 to 2010

1991 to 2000