Ancestral origin of ApoE ε4 Alzheimer disease risk in Puerto Rican and African American populations

Farid Rajabli, Briseida E. Feliciano, Katrina Celis, Kara L. Hamilton-Nelson, Patrice L. Whitehead, Larry D. Adams, Parker L. Bussies, Clara P. Manrique, Alejandra Rodriguez, Vanessa Rodriguez, Takiyah Starks, Grace E. Byfield, Carolina B. Sierra Lopez, Jacob L McCauley, Heriberto Acosta, Angel Chinea, Brian W. Kunkle, Christiane Reitz, Lindsay A. Farrer, Gerard D. SchellenbergBadri N. Vardarajan, Jeffery M Vance, Michael Cuccaro, Eden R Martin, Jonathan L. Haines, Goldie S. Byrd, Gary W Beecham, Margaret A Pericak-Vance

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The ApoE ε4 allele is the most significant genetic risk factor for late-onset Alzheimer disease. The risk conferred by ε4, however, differs across populations, with populations of African ancestry showing lower ε4 risk compared to those of European or Asian ancestry. The cause of this heterogeneity in risk effect is currently unknown; it may be due to environmental or cultural factors correlated with ancestry, or it may be due to genetic variation local to the ApoE region that differs among populations. Exploring these hypotheses may lead to novel, population-specific therapeutics and risk predictions. To test these hypotheses, we analyzed ApoE genotypes and genome-wide array data in individuals from African American and Puerto Rican populations. A total of 1,766 African American and 220 Puerto Rican individuals with late-onset Alzheimer disease, and 3,730 African American and 169 Puerto Rican cognitively healthy individuals (> 65 years) participated in the study. We first assessed average ancestry across the genome (“global” ancestry) and then tested it for interaction with ApoE genotypes. Next, we assessed the ancestral background of ApoE alleles (“local” ancestry) and tested if ancestry local to ApoE influenced Alzheimer disease risk while controlling for global ancestry. Measures of global ancestry showed no interaction with ApoE risk (Puerto Rican: p-value = 0.49; African American: p-value = 0.65). Conversely, ancestry local to the ApoE region showed an interaction with the ApoE ε4 allele in both populations (Puerto Rican: p-value = 0.019; African American: p-value = 0.005). ApoE ε4 alleles on an African background conferred a lower risk than those with a European ancestral background, regardless of population (Puerto Rican: OR = 1.26 on African background, OR = 4.49 on European; African American: OR = 2.34 on African background, OR = 3.05 on European background). Factors contributing to the lower risk effect in the ApoE gene ε4 allele are likely due to ancestry-specific genetic factors near ApoE rather than non-genetic ethnic, cultural, and environmental factors.

Original languageEnglish (US)
Article numbere1007791
JournalPLoS Genetics
Volume14
Issue number12
DOIs
StatePublished - Dec 1 2018

Fingerprint

African American
Apolipoproteins E
African Americans
Alzheimer disease
ancestry
Population
allele
Alleles
alleles
Alzheimer Disease
genotype
Alzheimer disease type 4
genome
Genotype
Genome
risk factor
genetic variation
environmental factor
risk factors

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

Rajabli, F., Feliciano, B. E., Celis, K., Hamilton-Nelson, K. L., Whitehead, P. L., Adams, L. D., ... Pericak-Vance, M. A. (2018). Ancestral origin of ApoE ε4 Alzheimer disease risk in Puerto Rican and African American populations. PLoS Genetics, 14(12), [e1007791]. https://doi.org/10.1371/journal.pgen.1007791

Ancestral origin of ApoE ε4 Alzheimer disease risk in Puerto Rican and African American populations. / Rajabli, Farid; Feliciano, Briseida E.; Celis, Katrina; Hamilton-Nelson, Kara L.; Whitehead, Patrice L.; Adams, Larry D.; Bussies, Parker L.; Manrique, Clara P.; Rodriguez, Alejandra; Rodriguez, Vanessa; Starks, Takiyah; Byfield, Grace E.; Sierra Lopez, Carolina B.; McCauley, Jacob L; Acosta, Heriberto; Chinea, Angel; Kunkle, Brian W.; Reitz, Christiane; Farrer, Lindsay A.; Schellenberg, Gerard D.; Vardarajan, Badri N.; Vance, Jeffery M; Cuccaro, Michael; Martin, Eden R; Haines, Jonathan L.; Byrd, Goldie S.; Beecham, Gary W; Pericak-Vance, Margaret A.

In: PLoS Genetics, Vol. 14, No. 12, e1007791, 01.12.2018.

Research output: Contribution to journalArticle

Rajabli, F, Feliciano, BE, Celis, K, Hamilton-Nelson, KL, Whitehead, PL, Adams, LD, Bussies, PL, Manrique, CP, Rodriguez, A, Rodriguez, V, Starks, T, Byfield, GE, Sierra Lopez, CB, McCauley, JL, Acosta, H, Chinea, A, Kunkle, BW, Reitz, C, Farrer, LA, Schellenberg, GD, Vardarajan, BN, Vance, JM, Cuccaro, M, Martin, ER, Haines, JL, Byrd, GS, Beecham, GW & Pericak-Vance, MA 2018, 'Ancestral origin of ApoE ε4 Alzheimer disease risk in Puerto Rican and African American populations', PLoS Genetics, vol. 14, no. 12, e1007791. https://doi.org/10.1371/journal.pgen.1007791
Rajabli F, Feliciano BE, Celis K, Hamilton-Nelson KL, Whitehead PL, Adams LD et al. Ancestral origin of ApoE ε4 Alzheimer disease risk in Puerto Rican and African American populations. PLoS Genetics. 2018 Dec 1;14(12). e1007791. https://doi.org/10.1371/journal.pgen.1007791
Rajabli, Farid ; Feliciano, Briseida E. ; Celis, Katrina ; Hamilton-Nelson, Kara L. ; Whitehead, Patrice L. ; Adams, Larry D. ; Bussies, Parker L. ; Manrique, Clara P. ; Rodriguez, Alejandra ; Rodriguez, Vanessa ; Starks, Takiyah ; Byfield, Grace E. ; Sierra Lopez, Carolina B. ; McCauley, Jacob L ; Acosta, Heriberto ; Chinea, Angel ; Kunkle, Brian W. ; Reitz, Christiane ; Farrer, Lindsay A. ; Schellenberg, Gerard D. ; Vardarajan, Badri N. ; Vance, Jeffery M ; Cuccaro, Michael ; Martin, Eden R ; Haines, Jonathan L. ; Byrd, Goldie S. ; Beecham, Gary W ; Pericak-Vance, Margaret A. / Ancestral origin of ApoE ε4 Alzheimer disease risk in Puerto Rican and African American populations. In: PLoS Genetics. 2018 ; Vol. 14, No. 12.
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title = "Ancestral origin of ApoE ε4 Alzheimer disease risk in Puerto Rican and African American populations",
abstract = "The ApoE ε4 allele is the most significant genetic risk factor for late-onset Alzheimer disease. The risk conferred by ε4, however, differs across populations, with populations of African ancestry showing lower ε4 risk compared to those of European or Asian ancestry. The cause of this heterogeneity in risk effect is currently unknown; it may be due to environmental or cultural factors correlated with ancestry, or it may be due to genetic variation local to the ApoE region that differs among populations. Exploring these hypotheses may lead to novel, population-specific therapeutics and risk predictions. To test these hypotheses, we analyzed ApoE genotypes and genome-wide array data in individuals from African American and Puerto Rican populations. A total of 1,766 African American and 220 Puerto Rican individuals with late-onset Alzheimer disease, and 3,730 African American and 169 Puerto Rican cognitively healthy individuals (> 65 years) participated in the study. We first assessed average ancestry across the genome (“global” ancestry) and then tested it for interaction with ApoE genotypes. Next, we assessed the ancestral background of ApoE alleles (“local” ancestry) and tested if ancestry local to ApoE influenced Alzheimer disease risk while controlling for global ancestry. Measures of global ancestry showed no interaction with ApoE risk (Puerto Rican: p-value = 0.49; African American: p-value = 0.65). Conversely, ancestry local to the ApoE region showed an interaction with the ApoE ε4 allele in both populations (Puerto Rican: p-value = 0.019; African American: p-value = 0.005). ApoE ε4 alleles on an African background conferred a lower risk than those with a European ancestral background, regardless of population (Puerto Rican: OR = 1.26 on African background, OR = 4.49 on European; African American: OR = 2.34 on African background, OR = 3.05 on European background). Factors contributing to the lower risk effect in the ApoE gene ε4 allele are likely due to ancestry-specific genetic factors near ApoE rather than non-genetic ethnic, cultural, and environmental factors.",
author = "Farid Rajabli and Feliciano, {Briseida E.} and Katrina Celis and Hamilton-Nelson, {Kara L.} and Whitehead, {Patrice L.} and Adams, {Larry D.} and Bussies, {Parker L.} and Manrique, {Clara P.} and Alejandra Rodriguez and Vanessa Rodriguez and Takiyah Starks and Byfield, {Grace E.} and {Sierra Lopez}, {Carolina B.} and McCauley, {Jacob L} and Heriberto Acosta and Angel Chinea and Kunkle, {Brian W.} and Christiane Reitz and Farrer, {Lindsay A.} and Schellenberg, {Gerard D.} and Vardarajan, {Badri N.} and Vance, {Jeffery M} and Michael Cuccaro and Martin, {Eden R} and Haines, {Jonathan L.} and Byrd, {Goldie S.} and Beecham, {Gary W} and Pericak-Vance, {Margaret A}",
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T1 - Ancestral origin of ApoE ε4 Alzheimer disease risk in Puerto Rican and African American populations

AU - Rajabli, Farid

AU - Feliciano, Briseida E.

AU - Celis, Katrina

AU - Hamilton-Nelson, Kara L.

AU - Whitehead, Patrice L.

AU - Adams, Larry D.

AU - Bussies, Parker L.

AU - Manrique, Clara P.

AU - Rodriguez, Alejandra

AU - Rodriguez, Vanessa

AU - Starks, Takiyah

AU - Byfield, Grace E.

AU - Sierra Lopez, Carolina B.

AU - McCauley, Jacob L

AU - Acosta, Heriberto

AU - Chinea, Angel

AU - Kunkle, Brian W.

AU - Reitz, Christiane

AU - Farrer, Lindsay A.

AU - Schellenberg, Gerard D.

AU - Vardarajan, Badri N.

AU - Vance, Jeffery M

AU - Cuccaro, Michael

AU - Martin, Eden R

AU - Haines, Jonathan L.

AU - Byrd, Goldie S.

AU - Beecham, Gary W

AU - Pericak-Vance, Margaret A

PY - 2018/12/1

Y1 - 2018/12/1

N2 - The ApoE ε4 allele is the most significant genetic risk factor for late-onset Alzheimer disease. The risk conferred by ε4, however, differs across populations, with populations of African ancestry showing lower ε4 risk compared to those of European or Asian ancestry. The cause of this heterogeneity in risk effect is currently unknown; it may be due to environmental or cultural factors correlated with ancestry, or it may be due to genetic variation local to the ApoE region that differs among populations. Exploring these hypotheses may lead to novel, population-specific therapeutics and risk predictions. To test these hypotheses, we analyzed ApoE genotypes and genome-wide array data in individuals from African American and Puerto Rican populations. A total of 1,766 African American and 220 Puerto Rican individuals with late-onset Alzheimer disease, and 3,730 African American and 169 Puerto Rican cognitively healthy individuals (> 65 years) participated in the study. We first assessed average ancestry across the genome (“global” ancestry) and then tested it for interaction with ApoE genotypes. Next, we assessed the ancestral background of ApoE alleles (“local” ancestry) and tested if ancestry local to ApoE influenced Alzheimer disease risk while controlling for global ancestry. Measures of global ancestry showed no interaction with ApoE risk (Puerto Rican: p-value = 0.49; African American: p-value = 0.65). Conversely, ancestry local to the ApoE region showed an interaction with the ApoE ε4 allele in both populations (Puerto Rican: p-value = 0.019; African American: p-value = 0.005). ApoE ε4 alleles on an African background conferred a lower risk than those with a European ancestral background, regardless of population (Puerto Rican: OR = 1.26 on African background, OR = 4.49 on European; African American: OR = 2.34 on African background, OR = 3.05 on European background). Factors contributing to the lower risk effect in the ApoE gene ε4 allele are likely due to ancestry-specific genetic factors near ApoE rather than non-genetic ethnic, cultural, and environmental factors.

AB - The ApoE ε4 allele is the most significant genetic risk factor for late-onset Alzheimer disease. The risk conferred by ε4, however, differs across populations, with populations of African ancestry showing lower ε4 risk compared to those of European or Asian ancestry. The cause of this heterogeneity in risk effect is currently unknown; it may be due to environmental or cultural factors correlated with ancestry, or it may be due to genetic variation local to the ApoE region that differs among populations. Exploring these hypotheses may lead to novel, population-specific therapeutics and risk predictions. To test these hypotheses, we analyzed ApoE genotypes and genome-wide array data in individuals from African American and Puerto Rican populations. A total of 1,766 African American and 220 Puerto Rican individuals with late-onset Alzheimer disease, and 3,730 African American and 169 Puerto Rican cognitively healthy individuals (> 65 years) participated in the study. We first assessed average ancestry across the genome (“global” ancestry) and then tested it for interaction with ApoE genotypes. Next, we assessed the ancestral background of ApoE alleles (“local” ancestry) and tested if ancestry local to ApoE influenced Alzheimer disease risk while controlling for global ancestry. Measures of global ancestry showed no interaction with ApoE risk (Puerto Rican: p-value = 0.49; African American: p-value = 0.65). Conversely, ancestry local to the ApoE region showed an interaction with the ApoE ε4 allele in both populations (Puerto Rican: p-value = 0.019; African American: p-value = 0.005). ApoE ε4 alleles on an African background conferred a lower risk than those with a European ancestral background, regardless of population (Puerto Rican: OR = 1.26 on African background, OR = 4.49 on European; African American: OR = 2.34 on African background, OR = 3.05 on European background). Factors contributing to the lower risk effect in the ApoE gene ε4 allele are likely due to ancestry-specific genetic factors near ApoE rather than non-genetic ethnic, cultural, and environmental factors.

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