Ancestry of the Timorese

Age-related macular degeneration associated genotype and allele sharing among human populations from throughout the world

Margaux A. Morrison, Tiago R. Magalhaes, Jacqueline Ramke, Silvia E. Smith, Sean Ennis, Claire Simpson, Laura Portas, Federico Murgia, Jeeyun Ahn, Caitlin Dardenne, Katie Mayne, Rosann Robinson, Denise J. Morgan, Garry Brian, Lucy Lee, Se J. Woo, Fani Zacharaki, Evangelia E. Tsironi, Joan W. Miller, Ivana K. Kim & 5 others Kyu H. Park, Joan E. Bailey-Wilson, Lindsay A. Farrer, Dwight Stambolian, Margaret M. DeAngelis

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

We observed that the third leading cause of blindness in the world, age-related macular degeneration (AMD), occurs at a very low documented frequency in a population-based cohort from Timor-Leste. Thus, we determined a complete catalog of the ancestry of the Timorese by analysis of whole exome chip data and haplogroup analysis of SNP genotypes determined by sequencing the Hypervariable I and II regions of the mitochondrial genome and 17 genotyped YSTR markers obtained from 535 individuals. We genotyped 20 previously reported AMD-associated SNPs in the Timorese to examine their allele frequencies compared to and between previously documented AMD cohorts of varying ethnicities. For those without AMD (average age > 55 years), genotype and allele frequencies were similar for most SNPs with a few exceptions. The major risk allele of HTRA1 rs11200638 (10q26) was at a significantly higher frequency in the Timorese, as well as 3 of the 5 protective CFH (1q32) SNPs (rs800292, rs2284664, and rs12066959). Additionally, the most commonly associated AMD-risk SNP, CFH rs1061170 (Y402H), was also seen at a much lower frequency in the Korean and Timorese populations than in the assessed Caucasian populations (C ~7 vs. ~40%, respectively). The difference in allele frequencies between the Timorese population and the other genotyped populations, along with the haplogroup analysis, also highlight the genetic diversity of the Timorese. Specifically, the most common ancestry groupings were Oceanic (Melanesian and Papuan) and Eastern Asian (specifically Han Chinese). The low prevalence of AMD in the Timorese population (2 of 535 randomly selected participants) may be due to the enrichment of protective alleles in this population at the 1q32 locus.

Original languageEnglish (US)
Article number238
JournalFrontiers in Genetics
Volume6
Issue numberJUL
DOIs
StatePublished - Jan 1 2015

Fingerprint

Macular Degeneration
Alleles
Genotype
Single Nucleotide Polymorphism
Population
Gene Frequency
Exome
Mitochondrial Genome
Blindness

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Genetics
  • Genetics(clinical)

Cite this

Ancestry of the Timorese : Age-related macular degeneration associated genotype and allele sharing among human populations from throughout the world. / Morrison, Margaux A.; Magalhaes, Tiago R.; Ramke, Jacqueline; Smith, Silvia E.; Ennis, Sean; Simpson, Claire; Portas, Laura; Murgia, Federico; Ahn, Jeeyun; Dardenne, Caitlin; Mayne, Katie; Robinson, Rosann; Morgan, Denise J.; Brian, Garry; Lee, Lucy; Woo, Se J.; Zacharaki, Fani; Tsironi, Evangelia E.; Miller, Joan W.; Kim, Ivana K.; Park, Kyu H.; Bailey-Wilson, Joan E.; Farrer, Lindsay A.; Stambolian, Dwight; DeAngelis, Margaret M.

In: Frontiers in Genetics, Vol. 6, No. JUL, 238, 01.01.2015.

Research output: Contribution to journalArticle

Morrison, MA, Magalhaes, TR, Ramke, J, Smith, SE, Ennis, S, Simpson, C, Portas, L, Murgia, F, Ahn, J, Dardenne, C, Mayne, K, Robinson, R, Morgan, DJ, Brian, G, Lee, L, Woo, SJ, Zacharaki, F, Tsironi, EE, Miller, JW, Kim, IK, Park, KH, Bailey-Wilson, JE, Farrer, LA, Stambolian, D & DeAngelis, MM 2015, 'Ancestry of the Timorese: Age-related macular degeneration associated genotype and allele sharing among human populations from throughout the world', Frontiers in Genetics, vol. 6, no. JUL, 238. https://doi.org/10.3389/fgene.2015.00238
Morrison, Margaux A. ; Magalhaes, Tiago R. ; Ramke, Jacqueline ; Smith, Silvia E. ; Ennis, Sean ; Simpson, Claire ; Portas, Laura ; Murgia, Federico ; Ahn, Jeeyun ; Dardenne, Caitlin ; Mayne, Katie ; Robinson, Rosann ; Morgan, Denise J. ; Brian, Garry ; Lee, Lucy ; Woo, Se J. ; Zacharaki, Fani ; Tsironi, Evangelia E. ; Miller, Joan W. ; Kim, Ivana K. ; Park, Kyu H. ; Bailey-Wilson, Joan E. ; Farrer, Lindsay A. ; Stambolian, Dwight ; DeAngelis, Margaret M. / Ancestry of the Timorese : Age-related macular degeneration associated genotype and allele sharing among human populations from throughout the world. In: Frontiers in Genetics. 2015 ; Vol. 6, No. JUL.
@article{67d3236deea24a509e5f9dae9f6751e0,
title = "Ancestry of the Timorese: Age-related macular degeneration associated genotype and allele sharing among human populations from throughout the world",
abstract = "We observed that the third leading cause of blindness in the world, age-related macular degeneration (AMD), occurs at a very low documented frequency in a population-based cohort from Timor-Leste. Thus, we determined a complete catalog of the ancestry of the Timorese by analysis of whole exome chip data and haplogroup analysis of SNP genotypes determined by sequencing the Hypervariable I and II regions of the mitochondrial genome and 17 genotyped YSTR markers obtained from 535 individuals. We genotyped 20 previously reported AMD-associated SNPs in the Timorese to examine their allele frequencies compared to and between previously documented AMD cohorts of varying ethnicities. For those without AMD (average age > 55 years), genotype and allele frequencies were similar for most SNPs with a few exceptions. The major risk allele of HTRA1 rs11200638 (10q26) was at a significantly higher frequency in the Timorese, as well as 3 of the 5 protective CFH (1q32) SNPs (rs800292, rs2284664, and rs12066959). Additionally, the most commonly associated AMD-risk SNP, CFH rs1061170 (Y402H), was also seen at a much lower frequency in the Korean and Timorese populations than in the assessed Caucasian populations (C ~7 vs. ~40{\%}, respectively). The difference in allele frequencies between the Timorese population and the other genotyped populations, along with the haplogroup analysis, also highlight the genetic diversity of the Timorese. Specifically, the most common ancestry groupings were Oceanic (Melanesian and Papuan) and Eastern Asian (specifically Han Chinese). The low prevalence of AMD in the Timorese population (2 of 535 randomly selected participants) may be due to the enrichment of protective alleles in this population at the 1q32 locus.",
author = "Morrison, {Margaux A.} and Magalhaes, {Tiago R.} and Jacqueline Ramke and Smith, {Silvia E.} and Sean Ennis and Claire Simpson and Laura Portas and Federico Murgia and Jeeyun Ahn and Caitlin Dardenne and Katie Mayne and Rosann Robinson and Morgan, {Denise J.} and Garry Brian and Lucy Lee and Woo, {Se J.} and Fani Zacharaki and Tsironi, {Evangelia E.} and Miller, {Joan W.} and Kim, {Ivana K.} and Park, {Kyu H.} and Bailey-Wilson, {Joan E.} and Farrer, {Lindsay A.} and Dwight Stambolian and DeAngelis, {Margaret M.}",
year = "2015",
month = "1",
day = "1",
doi = "10.3389/fgene.2015.00238",
language = "English (US)",
volume = "6",
journal = "Frontiers in Genetics",
issn = "1664-8021",
publisher = "Frontiers Media S. A.",
number = "JUL",

}

TY - JOUR

T1 - Ancestry of the Timorese

T2 - Age-related macular degeneration associated genotype and allele sharing among human populations from throughout the world

AU - Morrison, Margaux A.

AU - Magalhaes, Tiago R.

AU - Ramke, Jacqueline

AU - Smith, Silvia E.

AU - Ennis, Sean

AU - Simpson, Claire

AU - Portas, Laura

AU - Murgia, Federico

AU - Ahn, Jeeyun

AU - Dardenne, Caitlin

AU - Mayne, Katie

AU - Robinson, Rosann

AU - Morgan, Denise J.

AU - Brian, Garry

AU - Lee, Lucy

AU - Woo, Se J.

AU - Zacharaki, Fani

AU - Tsironi, Evangelia E.

AU - Miller, Joan W.

AU - Kim, Ivana K.

AU - Park, Kyu H.

AU - Bailey-Wilson, Joan E.

AU - Farrer, Lindsay A.

AU - Stambolian, Dwight

AU - DeAngelis, Margaret M.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - We observed that the third leading cause of blindness in the world, age-related macular degeneration (AMD), occurs at a very low documented frequency in a population-based cohort from Timor-Leste. Thus, we determined a complete catalog of the ancestry of the Timorese by analysis of whole exome chip data and haplogroup analysis of SNP genotypes determined by sequencing the Hypervariable I and II regions of the mitochondrial genome and 17 genotyped YSTR markers obtained from 535 individuals. We genotyped 20 previously reported AMD-associated SNPs in the Timorese to examine their allele frequencies compared to and between previously documented AMD cohorts of varying ethnicities. For those without AMD (average age > 55 years), genotype and allele frequencies were similar for most SNPs with a few exceptions. The major risk allele of HTRA1 rs11200638 (10q26) was at a significantly higher frequency in the Timorese, as well as 3 of the 5 protective CFH (1q32) SNPs (rs800292, rs2284664, and rs12066959). Additionally, the most commonly associated AMD-risk SNP, CFH rs1061170 (Y402H), was also seen at a much lower frequency in the Korean and Timorese populations than in the assessed Caucasian populations (C ~7 vs. ~40%, respectively). The difference in allele frequencies between the Timorese population and the other genotyped populations, along with the haplogroup analysis, also highlight the genetic diversity of the Timorese. Specifically, the most common ancestry groupings were Oceanic (Melanesian and Papuan) and Eastern Asian (specifically Han Chinese). The low prevalence of AMD in the Timorese population (2 of 535 randomly selected participants) may be due to the enrichment of protective alleles in this population at the 1q32 locus.

AB - We observed that the third leading cause of blindness in the world, age-related macular degeneration (AMD), occurs at a very low documented frequency in a population-based cohort from Timor-Leste. Thus, we determined a complete catalog of the ancestry of the Timorese by analysis of whole exome chip data and haplogroup analysis of SNP genotypes determined by sequencing the Hypervariable I and II regions of the mitochondrial genome and 17 genotyped YSTR markers obtained from 535 individuals. We genotyped 20 previously reported AMD-associated SNPs in the Timorese to examine their allele frequencies compared to and between previously documented AMD cohorts of varying ethnicities. For those without AMD (average age > 55 years), genotype and allele frequencies were similar for most SNPs with a few exceptions. The major risk allele of HTRA1 rs11200638 (10q26) was at a significantly higher frequency in the Timorese, as well as 3 of the 5 protective CFH (1q32) SNPs (rs800292, rs2284664, and rs12066959). Additionally, the most commonly associated AMD-risk SNP, CFH rs1061170 (Y402H), was also seen at a much lower frequency in the Korean and Timorese populations than in the assessed Caucasian populations (C ~7 vs. ~40%, respectively). The difference in allele frequencies between the Timorese population and the other genotyped populations, along with the haplogroup analysis, also highlight the genetic diversity of the Timorese. Specifically, the most common ancestry groupings were Oceanic (Melanesian and Papuan) and Eastern Asian (specifically Han Chinese). The low prevalence of AMD in the Timorese population (2 of 535 randomly selected participants) may be due to the enrichment of protective alleles in this population at the 1q32 locus.

UR - http://www.scopus.com/inward/record.url?scp=84940104627&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84940104627&partnerID=8YFLogxK

U2 - 10.3389/fgene.2015.00238

DO - 10.3389/fgene.2015.00238

M3 - Article

VL - 6

JO - Frontiers in Genetics

JF - Frontiers in Genetics

SN - 1664-8021

IS - JUL

M1 - 238

ER -