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.
Highlights
The population of Timor-Leste is afflicted by a very high prevalence of vision problems and ocular morbidity
A diagnosis of early age-related macular degeneration (AMD) was given to two subjects from the Timor population: a 62 year old female and a 75 year old male
AMD risk is explained by many other loci which implicate several mechanisms and pathways underlying AMD pathophysiology
Summary
The population of Timor-Leste is afflicted by a very high prevalence of vision problems and ocular morbidity. Previous ancestry studies of Southeast Asian populations considered only mitochondrial DNA (mtDNA) markers (e.g., Melton et al, 1998; Hill et al, 2007; Tabbada et al, 2010) Y-STRs (e.g., Kayser et al, 2001; Karafet et al, 2010; Zhong et al, 2011; Van Oven et al, 2012), or both (e.g., Kayser et al, 2003; Hurles et al, 2005; Mona et al, 2009; Stoneking and Delfin, 2010). These studies consistently showed a preponderance of Y haplogroups O and M, and mtDNA haplogroups M, B, and F, many other haplogroups are represented in Southeast Asia at lower frequencies
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