Frontiers in Aging Neuroscience (Sep 2024)
Genome-wide association analysis and admixture mapping in a Puerto Rican cohort supports an Alzheimer disease risk locus on chromosome 12
- Bilcag Akgun,
- Briseida E. Feliciano-Astacio,
- Kara L. Hamilton-Nelson,
- Kyle Scott,
- Joe Rivero,
- Larry D. Adams,
- Jose J. Sanchez,
- Glenies S. Valladares,
- Sergio Tejada,
- Parker L. Bussies,
- Concepcion Silva-Vergara,
- Vanessa C. Rodriguez,
- Pedro R. Mena,
- Katrina Celis,
- Patrice G. Whitehead,
- Michael Prough,
- Christina Kosanovic,
- Derek J. Van Booven,
- Michael A. Schmidt,
- Heriberto Acosta,
- Anthony J. Griswold,
- Anthony J. Griswold,
- Clifton L. Dalgard,
- Katalina F. McInerney,
- Gary W. Beecham,
- Gary W. Beecham,
- Michael L. Cuccaro,
- Michael L. Cuccaro,
- Jeffery M. Vance,
- Jeffery M. Vance,
- Jeffery M. Vance,
- Margaret A. Pericak-Vance,
- Margaret A. Pericak-Vance,
- Margaret A. Pericak-Vance,
- Farid Rajabli,
- Farid Rajabli
Affiliations
- Bilcag Akgun
- John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, United States
- Briseida E. Feliciano-Astacio
- Universidad Central del Caribe, Bayamón, PR, United States
- Kara L. Hamilton-Nelson
- John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, United States
- Kyle Scott
- John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, United States
- Joe Rivero
- John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, United States
- Larry D. Adams
- John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, United States
- Jose J. Sanchez
- John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, United States
- Glenies S. Valladares
- John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, United States
- Sergio Tejada
- John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, United States
- Parker L. Bussies
- John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, United States
- Concepcion Silva-Vergara
- John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, United States
- Vanessa C. Rodriguez
- John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, United States
- Pedro R. Mena
- John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, United States
- Katrina Celis
- John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, United States
- Patrice G. Whitehead
- John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, United States
- Michael Prough
- John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, United States
- Christina Kosanovic
- John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, United States
- Derek J. Van Booven
- John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, United States
- Michael A. Schmidt
- John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, United States
- Heriberto Acosta
- Clinica de la Memoria, San Juan, PR, United States
- Anthony J. Griswold
- John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, United States
- Anthony J. Griswold
- Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, United States
- Clifton L. Dalgard
- Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, United States
- Katalina F. McInerney
- Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, United States
- Gary W. Beecham
- John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, United States
- Gary W. Beecham
- Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, United States
- Michael L. Cuccaro
- John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, United States
- Michael L. Cuccaro
- Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, United States
- Jeffery M. Vance
- John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, United States
- Jeffery M. Vance
- Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, United States
- Jeffery M. Vance
- Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, United States
- Margaret A. Pericak-Vance
- John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, United States
- Margaret A. Pericak-Vance
- Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, United States
- Margaret A. Pericak-Vance
- Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, United States
- Farid Rajabli
- John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, United States
- Farid Rajabli
- Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, United States
- DOI
- https://doi.org/10.3389/fnagi.2024.1459796
- Journal volume & issue
-
Vol. 16
Abstract
IntroductionHispanic/Latino populations are underrepresented in Alzheimer Disease (AD) genetic studies. Puerto Ricans (PR), a three-way admixed (European, African, and Amerindian) population is the second-largest Hispanic group in the continental US. We aimed to conduct a genome-wide association study (GWAS) and comprehensive analyses to identify novel AD susceptibility loci and characterize known AD genetic risk loci in the PR population.Materials and methodsOur study included Whole Genome Sequencing (WGS) and phenotype data from 648 PR individuals (345 AD, 303 cognitively unimpaired). We used a generalized linear-mixed model adjusting for sex, age, population substructure, and genetic relationship matrix. To infer local ancestry, we merged the dataset with the HGDP/1000G reference panel. Subsequently, we conducted univariate admixture mapping (AM) analysis.ResultsWe identified suggestive signals within the SLC38A1 and SCN8A genes on chromosome 12q13. This region overlaps with an area of linkage of AD in previous studies (12q13) in independent data sets further supporting. Univariate African AM analysis identified one suggestive ancestral block (p = 7.2×10−6) located in the same region. The ancestry-aware approach showed that this region has both European and African ancestral backgrounds and both contributing to the risk in this region. We also replicated 11 different known AD loci -including APOE- identified in mostly European studies, which is likely due to the high European background of the PR population.ConclusionPR GWAS and AM analysis identified a suggestive AD risk locus on chromosome 12, which includes the SLC38A1 and SCN8A genes. Our findings demonstrate the importance of designing GWAS and ancestry-aware approaches and including underrepresented populations in genetic studies of AD.
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