Native ancestry is associated with optic neuritis and age of onset in hispanics with multiple sclerosis

Lilyana Amezcua, Ashley H. Beecham, Silvia Delgado, Angel Chinea, Margaret Burnett, Clara Patricia Manrique, Refujia Gomez, Manuel Comabella, Xavier Montalban, Melissa Ortega, Leticia Tornes, Brett T. Lund, Talat Islam, David Conti, Jorge R. Oksenberg, Jacob L McCauley

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background and Objective: Hispanics with multiple sclerosis (MS) present younger and more often with optic neuritis (ON) as compared to Whites in the western United States. Regional differences related to Hispanic genetic admixture could be responsible. We investigated the association between global genetic ancestry and ON and age at onset of MS in Hispanics. Methods: Data were obtained for 1033 self-identified Hispanics with MS from four MS-based registries from four academic institutions across the United States January 2016–April 2017. Multivariate regression models, utilizing genetic ancestry estimates for Native American (NA), African, and European ancestry, were used to assess the relationship between genetic ancestry and ON presentation and age of MS onset, defined as age at first symptom. Results: Genetic ancestry and ON proportions varied by region where NA ancestry and ON proportions were highest among Hispanics in the southwestern United States (40% vs. 19% overall for NA and 38% vs. 25% overall for ON). A strong inverse correlation was observed between NA and European ancestry (r = −0.83). ON presentation was associated with younger age of onset (OR: 0.98; 95% CI: 0.96–0.99; P = 7.80 × 10−03) and increased NA ancestry (OR: 2.35 for the highest versus the lowest quartile of NA ancestry; 95% CI: 1.35–4.10; P = 2.60 × 10−03). Younger age of onset was found to be associated with a higher proportion NA (Beta: −5.58; P = 3.49 × 10−02) and African ancestry (Beta: −10.07; P = 1.39 × 10−03). Interpretation: Ethnic differences associated with genetic admixture could influence clinical presentation in Hispanics with MS; underscoring the importance of considering genetic substructure in future clinical, genetic, and epigenetic studies in Hispanics.

Original languageEnglish (US)
JournalAnnals of Clinical and Translational Neurology
DOIs
StateAccepted/In press - Jan 1 2018

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Optic Neuritis
North American Indians
Age of Onset
Population Groups
Hispanic Americans
Multiple Sclerosis
Southwestern United States
Genetic Models
Epigenomics
Registries

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

Cite this

Native ancestry is associated with optic neuritis and age of onset in hispanics with multiple sclerosis. / Amezcua, Lilyana; Beecham, Ashley H.; Delgado, Silvia; Chinea, Angel; Burnett, Margaret; Manrique, Clara Patricia; Gomez, Refujia; Comabella, Manuel; Montalban, Xavier; Ortega, Melissa; Tornes, Leticia; Lund, Brett T.; Islam, Talat; Conti, David; Oksenberg, Jorge R.; McCauley, Jacob L.

In: Annals of Clinical and Translational Neurology, 01.01.2018.

Research output: Contribution to journalArticle

Amezcua, L, Beecham, AH, Delgado, S, Chinea, A, Burnett, M, Manrique, CP, Gomez, R, Comabella, M, Montalban, X, Ortega, M, Tornes, L, Lund, BT, Islam, T, Conti, D, Oksenberg, JR & McCauley, JL 2018, 'Native ancestry is associated with optic neuritis and age of onset in hispanics with multiple sclerosis', Annals of Clinical and Translational Neurology. https://doi.org/10.1002/acn3.646
Amezcua, Lilyana ; Beecham, Ashley H. ; Delgado, Silvia ; Chinea, Angel ; Burnett, Margaret ; Manrique, Clara Patricia ; Gomez, Refujia ; Comabella, Manuel ; Montalban, Xavier ; Ortega, Melissa ; Tornes, Leticia ; Lund, Brett T. ; Islam, Talat ; Conti, David ; Oksenberg, Jorge R. ; McCauley, Jacob L. / Native ancestry is associated with optic neuritis and age of onset in hispanics with multiple sclerosis. In: Annals of Clinical and Translational Neurology. 2018.
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title = "Native ancestry is associated with optic neuritis and age of onset in hispanics with multiple sclerosis",
abstract = "Background and Objective: Hispanics with multiple sclerosis (MS) present younger and more often with optic neuritis (ON) as compared to Whites in the western United States. Regional differences related to Hispanic genetic admixture could be responsible. We investigated the association between global genetic ancestry and ON and age at onset of MS in Hispanics. Methods: Data were obtained for 1033 self-identified Hispanics with MS from four MS-based registries from four academic institutions across the United States January 2016–April 2017. Multivariate regression models, utilizing genetic ancestry estimates for Native American (NA), African, and European ancestry, were used to assess the relationship between genetic ancestry and ON presentation and age of MS onset, defined as age at first symptom. Results: Genetic ancestry and ON proportions varied by region where NA ancestry and ON proportions were highest among Hispanics in the southwestern United States (40{\%} vs. 19{\%} overall for NA and 38{\%} vs. 25{\%} overall for ON). A strong inverse correlation was observed between NA and European ancestry (r = −0.83). ON presentation was associated with younger age of onset (OR: 0.98; 95{\%} CI: 0.96–0.99; P = 7.80 × 10−03) and increased NA ancestry (OR: 2.35 for the highest versus the lowest quartile of NA ancestry; 95{\%} CI: 1.35–4.10; P = 2.60 × 10−03). Younger age of onset was found to be associated with a higher proportion NA (Beta: −5.58; P = 3.49 × 10−02) and African ancestry (Beta: −10.07; P = 1.39 × 10−03). Interpretation: Ethnic differences associated with genetic admixture could influence clinical presentation in Hispanics with MS; underscoring the importance of considering genetic substructure in future clinical, genetic, and epigenetic studies in Hispanics.",
author = "Lilyana Amezcua and Beecham, {Ashley H.} and Silvia Delgado and Angel Chinea and Margaret Burnett and Manrique, {Clara Patricia} and Refujia Gomez and Manuel Comabella and Xavier Montalban and Melissa Ortega and Leticia Tornes and Lund, {Brett T.} and Talat Islam and David Conti and Oksenberg, {Jorge R.} and McCauley, {Jacob L}",
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T1 - Native ancestry is associated with optic neuritis and age of onset in hispanics with multiple sclerosis

AU - Amezcua, Lilyana

AU - Beecham, Ashley H.

AU - Delgado, Silvia

AU - Chinea, Angel

AU - Burnett, Margaret

AU - Manrique, Clara Patricia

AU - Gomez, Refujia

AU - Comabella, Manuel

AU - Montalban, Xavier

AU - Ortega, Melissa

AU - Tornes, Leticia

AU - Lund, Brett T.

AU - Islam, Talat

AU - Conti, David

AU - Oksenberg, Jorge R.

AU - McCauley, Jacob L

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background and Objective: Hispanics with multiple sclerosis (MS) present younger and more often with optic neuritis (ON) as compared to Whites in the western United States. Regional differences related to Hispanic genetic admixture could be responsible. We investigated the association between global genetic ancestry and ON and age at onset of MS in Hispanics. Methods: Data were obtained for 1033 self-identified Hispanics with MS from four MS-based registries from four academic institutions across the United States January 2016–April 2017. Multivariate regression models, utilizing genetic ancestry estimates for Native American (NA), African, and European ancestry, were used to assess the relationship between genetic ancestry and ON presentation and age of MS onset, defined as age at first symptom. Results: Genetic ancestry and ON proportions varied by region where NA ancestry and ON proportions were highest among Hispanics in the southwestern United States (40% vs. 19% overall for NA and 38% vs. 25% overall for ON). A strong inverse correlation was observed between NA and European ancestry (r = −0.83). ON presentation was associated with younger age of onset (OR: 0.98; 95% CI: 0.96–0.99; P = 7.80 × 10−03) and increased NA ancestry (OR: 2.35 for the highest versus the lowest quartile of NA ancestry; 95% CI: 1.35–4.10; P = 2.60 × 10−03). Younger age of onset was found to be associated with a higher proportion NA (Beta: −5.58; P = 3.49 × 10−02) and African ancestry (Beta: −10.07; P = 1.39 × 10−03). Interpretation: Ethnic differences associated with genetic admixture could influence clinical presentation in Hispanics with MS; underscoring the importance of considering genetic substructure in future clinical, genetic, and epigenetic studies in Hispanics.

AB - Background and Objective: Hispanics with multiple sclerosis (MS) present younger and more often with optic neuritis (ON) as compared to Whites in the western United States. Regional differences related to Hispanic genetic admixture could be responsible. We investigated the association between global genetic ancestry and ON and age at onset of MS in Hispanics. Methods: Data were obtained for 1033 self-identified Hispanics with MS from four MS-based registries from four academic institutions across the United States January 2016–April 2017. Multivariate regression models, utilizing genetic ancestry estimates for Native American (NA), African, and European ancestry, were used to assess the relationship between genetic ancestry and ON presentation and age of MS onset, defined as age at first symptom. Results: Genetic ancestry and ON proportions varied by region where NA ancestry and ON proportions were highest among Hispanics in the southwestern United States (40% vs. 19% overall for NA and 38% vs. 25% overall for ON). A strong inverse correlation was observed between NA and European ancestry (r = −0.83). ON presentation was associated with younger age of onset (OR: 0.98; 95% CI: 0.96–0.99; P = 7.80 × 10−03) and increased NA ancestry (OR: 2.35 for the highest versus the lowest quartile of NA ancestry; 95% CI: 1.35–4.10; P = 2.60 × 10−03). Younger age of onset was found to be associated with a higher proportion NA (Beta: −5.58; P = 3.49 × 10−02) and African ancestry (Beta: −10.07; P = 1.39 × 10−03). Interpretation: Ethnic differences associated with genetic admixture could influence clinical presentation in Hispanics with MS; underscoring the importance of considering genetic substructure in future clinical, genetic, and epigenetic studies in Hispanics.

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