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Prevalence of common disease-associated variants in Asian Indians.

Pemberton TJ, Mehta NU, Witonsky D, Di Rienzo A, Allayee H, Conti DV, Patel PI - BMC Genet. (2008)

Bottom Line: In addition, we examined polymorphisms associated with skin pigmentation (SLC24A5) and with the ability to taste phenylthiocarbamide (TAS2R38).Although caution is warranted due to the fact that this US-sampled Indian cohort may not represent a random sample from India, our results will hopefully assist in the design of future studies that investigate the genetic causes of these diseases in India.Our results also support the inclusion of the Indian population in disease-related genetic studies, as it exhibits unique genotype as well as phenotype characteristics that may yield new insights into the underlying causes of common diseases that are not available in other populations.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. trevorp@usc.edu

ABSTRACT

Background: Asian Indians display a high prevalence of diseases linked to changes in diet and environment that have arisen as their lifestyle has become more westernized. Using 1200 genome-wide polymorphisms in 432 individuals from 15 Indian language groups, we have recently shown that: (i) Indians constitute a distinct population-genetic cluster, and (ii) despite the geographic and linguistic diversity of the groups they exhibit a relatively low level of genetic heterogeneity.

Results: We investigated the prevalence of common polymorphisms that have been associated with diseases, such as atherosclerosis (ALOX5), hypertension (CYP3A5, AGT, GNB3), diabetes (CAPN10, TCF7L2, PTPN22), prostate cancer (DG8S737, rs1447295), Hirschsprung disease (RET), and age-related macular degeneration (CFH, LOC387715). In addition, we examined polymorphisms associated with skin pigmentation (SLC24A5) and with the ability to taste phenylthiocarbamide (TAS2R38). All polymorphisms were studied in a cohort of 576 India-born Asian Indians sampled in the United States. This sample consisted of individuals whose mother tongue is one of 14 of the 22 "official" languages recognized in India as well as individuals whose mother tongue is Parsi, a cultural group that has resided in India for over 1000 years. Analysis of the data revealed that allele frequency differences between the different Indian language groups were small, and interestingly the variant alleles of ALOX5 g.8322G>A and g.50778G>A, and PTPN22 g.36677C>T were present only in a subset of the Indian language groups. Furthermore, a latitudinal cline was identified both for the allele frequencies of the SNPs associated with hypertension (CYP3A5, AGT, GNB3), as well as for those associated with the ability to taste phenylthiocarbamide (TAS2R38).

Conclusion: Although caution is warranted due to the fact that this US-sampled Indian cohort may not represent a random sample from India, our results will hopefully assist in the design of future studies that investigate the genetic causes of these diseases in India. Our results also support the inclusion of the Indian population in disease-related genetic studies, as it exhibits unique genotype as well as phenotype characteristics that may yield new insights into the underlying causes of common diseases that are not available in other populations.

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The correlation between latitude and minor allele frequency of the TAS2R38 SNPs (A) g.144G>C, (B) g.784C>T, and (C) g.885A>G. Correlation coefficients for each graph can be found in Table 15.
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Figure 3: The correlation between latitude and minor allele frequency of the TAS2R38 SNPs (A) g.144G>C, (B) g.784C>T, and (C) g.885A>G. Correlation coefficients for each graph can be found in Table 15.

Mentions: As observed above, the Kashmiri group had the highest MAFs for all three TAS2R38 SNPs and the Kannada group had the lowest (Table 4). Based on their relative frequencies, the Kashmiri would therefore be expected to have twice the number of tasters as the Kannada. The Kashmiri are one of the most northerly groups and the Kannada one of the most southerly (Figure 1), suggesting a possible latitudinal cline for the ability to taste PTC, with the greatest number of tasters in the northern groups and the least in the southern groups. This is supported by the MAF of the three SNPs in the other Indian language groups (Figure 3; Table 15). However, only the TAS2R38 g.144G>C SNP follows the same trend in both the Indian groups and in the other available world populations (Figure 3A; see Additional file 1, Table S18). For both the TAS2R38 g.784C>T and g.885A>G, the trend observed with the other world populations is the opposite of that observed with the Indian language groups (Figures 3B &3C, respectively; see Additional file 1, Tables S19 & S20, respectively). For example, the Indian groups display a decrease in MAF as the distance from the equator decreases, whereas other world populations demonstrate an increase in MAF as the distance from the equator decreases. The correlation between frequency and latitude was found to be the strongest for the TAS2R38 g.144G>C SNP, both when the Indian groups and the other world populations were considered separately and when they were combined (Table 15; Figure 3A &3B). The correlation was weakest for the TAS2R38 g.885A>G SNP, where it was still appreciable for the Indian groups, but less so for the other world populations (Table 15; Figure 3C).


Prevalence of common disease-associated variants in Asian Indians.

Pemberton TJ, Mehta NU, Witonsky D, Di Rienzo A, Allayee H, Conti DV, Patel PI - BMC Genet. (2008)

The correlation between latitude and minor allele frequency of the TAS2R38 SNPs (A) g.144G>C, (B) g.784C>T, and (C) g.885A>G. Correlation coefficients for each graph can be found in Table 15.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2267478&req=5

Figure 3: The correlation between latitude and minor allele frequency of the TAS2R38 SNPs (A) g.144G>C, (B) g.784C>T, and (C) g.885A>G. Correlation coefficients for each graph can be found in Table 15.
Mentions: As observed above, the Kashmiri group had the highest MAFs for all three TAS2R38 SNPs and the Kannada group had the lowest (Table 4). Based on their relative frequencies, the Kashmiri would therefore be expected to have twice the number of tasters as the Kannada. The Kashmiri are one of the most northerly groups and the Kannada one of the most southerly (Figure 1), suggesting a possible latitudinal cline for the ability to taste PTC, with the greatest number of tasters in the northern groups and the least in the southern groups. This is supported by the MAF of the three SNPs in the other Indian language groups (Figure 3; Table 15). However, only the TAS2R38 g.144G>C SNP follows the same trend in both the Indian groups and in the other available world populations (Figure 3A; see Additional file 1, Table S18). For both the TAS2R38 g.784C>T and g.885A>G, the trend observed with the other world populations is the opposite of that observed with the Indian language groups (Figures 3B &3C, respectively; see Additional file 1, Tables S19 & S20, respectively). For example, the Indian groups display a decrease in MAF as the distance from the equator decreases, whereas other world populations demonstrate an increase in MAF as the distance from the equator decreases. The correlation between frequency and latitude was found to be the strongest for the TAS2R38 g.144G>C SNP, both when the Indian groups and the other world populations were considered separately and when they were combined (Table 15; Figure 3A &3B). The correlation was weakest for the TAS2R38 g.885A>G SNP, where it was still appreciable for the Indian groups, but less so for the other world populations (Table 15; Figure 3C).

Bottom Line: In addition, we examined polymorphisms associated with skin pigmentation (SLC24A5) and with the ability to taste phenylthiocarbamide (TAS2R38).Although caution is warranted due to the fact that this US-sampled Indian cohort may not represent a random sample from India, our results will hopefully assist in the design of future studies that investigate the genetic causes of these diseases in India.Our results also support the inclusion of the Indian population in disease-related genetic studies, as it exhibits unique genotype as well as phenotype characteristics that may yield new insights into the underlying causes of common diseases that are not available in other populations.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. trevorp@usc.edu

ABSTRACT

Background: Asian Indians display a high prevalence of diseases linked to changes in diet and environment that have arisen as their lifestyle has become more westernized. Using 1200 genome-wide polymorphisms in 432 individuals from 15 Indian language groups, we have recently shown that: (i) Indians constitute a distinct population-genetic cluster, and (ii) despite the geographic and linguistic diversity of the groups they exhibit a relatively low level of genetic heterogeneity.

Results: We investigated the prevalence of common polymorphisms that have been associated with diseases, such as atherosclerosis (ALOX5), hypertension (CYP3A5, AGT, GNB3), diabetes (CAPN10, TCF7L2, PTPN22), prostate cancer (DG8S737, rs1447295), Hirschsprung disease (RET), and age-related macular degeneration (CFH, LOC387715). In addition, we examined polymorphisms associated with skin pigmentation (SLC24A5) and with the ability to taste phenylthiocarbamide (TAS2R38). All polymorphisms were studied in a cohort of 576 India-born Asian Indians sampled in the United States. This sample consisted of individuals whose mother tongue is one of 14 of the 22 "official" languages recognized in India as well as individuals whose mother tongue is Parsi, a cultural group that has resided in India for over 1000 years. Analysis of the data revealed that allele frequency differences between the different Indian language groups were small, and interestingly the variant alleles of ALOX5 g.8322G>A and g.50778G>A, and PTPN22 g.36677C>T were present only in a subset of the Indian language groups. Furthermore, a latitudinal cline was identified both for the allele frequencies of the SNPs associated with hypertension (CYP3A5, AGT, GNB3), as well as for those associated with the ability to taste phenylthiocarbamide (TAS2R38).

Conclusion: Although caution is warranted due to the fact that this US-sampled Indian cohort may not represent a random sample from India, our results will hopefully assist in the design of future studies that investigate the genetic causes of these diseases in India. Our results also support the inclusion of the Indian population in disease-related genetic studies, as it exhibits unique genotype as well as phenotype characteristics that may yield new insights into the underlying causes of common diseases that are not available in other populations.

Show MeSH
Related in: MedlinePlus