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.
authors.affiliation: Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah Salt Lake City, UT, USA.
authors.forename: Margaux A
authors.initials: MA
authors.lastname: Morrison
authors.affiliation: National Children's Research Centre, Our Lady's Children's Hospital Dublin, Ireland ; Academic Centre on Rare Diseases, School of Medicine and Medical Science, University College Dublin Dublin, Ireland.
authors.forename: Tiago R
authors.initials: TR
authors.lastname: Magalhaes
authors.affiliation: The Fred Hollows Foundation New Zealand Auckland, New Zealand.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Ramke
authors.affiliation: Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah Salt Lake City, UT, USA.
authors.forename: Silvia E
authors.initials: SE
authors.lastname: Smith
authors.affiliation: Academic Centre on Rare Diseases, School of Medicine and Medical Science, University College Dublin Dublin, Ireland ; National Centre for Medical Genetics, Our Lady's Children's Hospital Dublin, Ireland.
authors.forename: Sean
authors.initials: S
authors.lastname: Ennis
authors.affiliation: Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health Baltimore, MD, USA.
authors.forename: Claire L
authors.initials: CL
authors.lastname: Simpson
authors.affiliation: Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health Baltimore, MD, USA ; Institute of Population Genetics, The National Research Council Sassari, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Portas
authors.affiliation: Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health Baltimore, MD, USA ; Institute of Population Genetics, The National Research Council Sassari, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Murgia
authors.affiliation: Department of Ophthalmology, Seoul National University College of Medicine Seoul, South Korea ; Department of Ophthalmology, Seoul Metropolitan Government Seoul National University Boramae Medical Center Seoul, South Korea.
authors.forename: Jeeyun
authors.initials: J
authors.lastname: Ahn
authors.affiliation: Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah Salt Lake City, UT, USA.
authors.forename: Caitlin
authors.initials: C
authors.lastname: Dardenne
authors.affiliation: Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah Salt Lake City, UT, USA.
authors.forename: Katie
authors.initials: K
authors.lastname: Mayne
authors.affiliation: Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah Salt Lake City, UT, USA.
authors.forename: Rosann
authors.initials: R
authors.lastname: Robinson
authors.affiliation: Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah Salt Lake City, UT, USA.
authors.forename: Denise J
authors.initials: DJ
authors.lastname: Morgan
authors.affiliation: The Fred Hollows Foundation New Zealand Auckland, New Zealand.
authors.forename: Garry
authors.initials: G
authors.lastname: Brian
authors.affiliation: The Fred Hollows Foundation New Zealand Auckland, New Zealand ; London School of Hygiene and Tropical Medicine, University of London London, UK.
authors.forename: Lucy
authors.initials: L
authors.lastname: Lee
authors.affiliation: Department of Ophthalmology, Seoul National University College of Medicine Seoul, South Korea ; Department of Ophthalmology, Seoul National University Bundang Hospital Seoungnam, South Korea.
authors.forename: Se J
authors.initials: SJ
authors.lastname: Woo
authors.affiliation: Department of Ophthalmology, University of Thessaly School of Medicine Larissa, Greece.
authors.forename: Fani
authors.initials: F
authors.lastname: Zacharaki
authors.affiliation: Department of Ophthalmology, University of Thessaly School of Medicine Larissa, Greece.
authors.forename: Evangelia E
authors.initials: EE
authors.lastname: Tsironi
authors.affiliation: Retina Service and Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School Boston, MA, USA.
authors.forename: Joan W
authors.initials: JW
authors.lastname: Miller
authors.affiliation: Retina Service and Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School Boston, MA, USA.
authors.forename: Ivana K
authors.initials: IK
authors.lastname: Kim
authors.affiliation: Department of Ophthalmology, Seoul National University College of Medicine Seoul, South Korea ; Department of Ophthalmology, Seoul National University Bundang Hospital Seoungnam, South Korea.
authors.forename: Kyu H
authors.initials: KH
authors.lastname: Park
authors.affiliation: Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health Baltimore, MD, USA.
authors.forename: Joan E
authors.initials: JE
authors.lastname: Bailey-Wilson
authors.affiliation: Departments of Medicine, Ophthalmology, Neurology, Epidemiology, and Biostatistics, Boston University Schools of Medicine and Public Health Boston, MA, USA.
authors.forename: Lindsay A
authors.initials: LA
authors.lastname: Farrer
authors.affiliation: Department of Ophthalmology, University of Pennsylvania Philadelphia, PA, USA.
authors.forename: Dwight
authors.initials: D
authors.lastname: Stambolian
authors.affiliation: Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah Salt Lake City, UT, USA.
authors.forename: Margaret M
authors.initials: MM
authors.lastname: DeAngelis
keywords: age-related macular degeneration; ancestry; and epidemiology; complex disease; population genetics