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Ancestry of the Timorese: age-related macular degeneration associated genotype and allele sharing among human populations from throughout the world.

Morrison MA, Magalhaes TR, Ramke J, Smith SE, Ennis S, Simpson CL, 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 - Front Genet (2015)

Bottom Line: 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.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).

View Article: PubMed Central - PubMed

Affiliation: Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah Salt Lake City, UT, USA.

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.

No MeSH data available.


Related in: MedlinePlus

Principal Component Analysis. Principal component 1, PC1, as calculated for each of the 51 HGDP references and compared to the Timorese individuals investigated in this study. The Y-axis shows each of the reference populations. The X-axis shows the calculated PC1 value for each population.
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Figure 3: Principal Component Analysis. Principal component 1, PC1, as calculated for each of the 51 HGDP references and compared to the Timorese individuals investigated in this study. The Y-axis shows each of the reference populations. The X-axis shows the calculated PC1 value for each population.

Mentions: After QC and data cleaning, genotypes from 253,405 SNPs were available for 489 Timorese subjects with a call rate of >98% and were included in the subsequent analyses. There were 11,064 common SNPs between the HGDP dataset and the Timorese dataset used for subsequent ancestry analyses. Principal components analysis showed that the first principal component, PC1, was most similar between the Timorese and Papuans, followed by the She, Tujia, Dai, and Han Chinese (mean PC1 ~ −0.02; Figure 3). Using admixture, we have used several number of groupings and have found that K = 5 organizes the populations into the known ancestral populations, i.e., African, Indo-European, Oceania, Amerindian and Asian. Those global ancestry components allow us to separate HGDP, a dataset with worldwide coverage into their well-established continental differences since the known populations are correctly assigned. Where k = 5, the Timorese samples were showing the greatest proportion of Admix group 2, followed by a smaller proportion of Admix group 4 (Figure 4A). Individuals with the highest values for Admix group 2 are mostly of Oceanic populations, such as the Melanesian and Papuan samples, which are geographically close to Timor-Leste. Individuals with high values for Admix group 4 are from Eastern Asia, including Japanese and several Chinese populations. By increasing the number of ancestral assignments (k) to 10, there is a clearer separation of the Timorese samples, in that they show a closer relationship with the Papuan samples, and not as much the Melanesian (Figure 4B). Using Ancestry Mapper, the largest percentage of the Timorese was assigned to the Han Chinese reference population (~85%, Figure 5).


Ancestry of the Timorese: age-related macular degeneration associated genotype and allele sharing among human populations from throughout the world.

Morrison MA, Magalhaes TR, Ramke J, Smith SE, Ennis S, Simpson CL, 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 - Front Genet (2015)

Principal Component Analysis. Principal component 1, PC1, as calculated for each of the 51 HGDP references and compared to the Timorese individuals investigated in this study. The Y-axis shows each of the reference populations. The X-axis shows the calculated PC1 value for each population.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496576&req=5

Figure 3: Principal Component Analysis. Principal component 1, PC1, as calculated for each of the 51 HGDP references and compared to the Timorese individuals investigated in this study. The Y-axis shows each of the reference populations. The X-axis shows the calculated PC1 value for each population.
Mentions: After QC and data cleaning, genotypes from 253,405 SNPs were available for 489 Timorese subjects with a call rate of >98% and were included in the subsequent analyses. There were 11,064 common SNPs between the HGDP dataset and the Timorese dataset used for subsequent ancestry analyses. Principal components analysis showed that the first principal component, PC1, was most similar between the Timorese and Papuans, followed by the She, Tujia, Dai, and Han Chinese (mean PC1 ~ −0.02; Figure 3). Using admixture, we have used several number of groupings and have found that K = 5 organizes the populations into the known ancestral populations, i.e., African, Indo-European, Oceania, Amerindian and Asian. Those global ancestry components allow us to separate HGDP, a dataset with worldwide coverage into their well-established continental differences since the known populations are correctly assigned. Where k = 5, the Timorese samples were showing the greatest proportion of Admix group 2, followed by a smaller proportion of Admix group 4 (Figure 4A). Individuals with the highest values for Admix group 2 are mostly of Oceanic populations, such as the Melanesian and Papuan samples, which are geographically close to Timor-Leste. Individuals with high values for Admix group 4 are from Eastern Asia, including Japanese and several Chinese populations. By increasing the number of ancestral assignments (k) to 10, there is a clearer separation of the Timorese samples, in that they show a closer relationship with the Papuan samples, and not as much the Melanesian (Figure 4B). Using Ancestry Mapper, the largest percentage of the Timorese was assigned to the Han Chinese reference population (~85%, Figure 5).

Bottom Line: 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.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).

View Article: PubMed Central - PubMed

Affiliation: Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah Salt Lake City, UT, USA.

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.

No MeSH data available.


Related in: MedlinePlus