Physiogenomic analysis of the Puerto Rican population

Abstract

Aims: Admixture in the population of the island of Puerto Rico is of general interest with regards to pharmacogenetics to develop comprehensive strategies for personalized healthcare in Latin Americans. This research was aimed at determining the frequencies of SNPs in key physiological, pharmacological and biochemical genes to infer population structure and ancestry in the Puerto Rican population.

Materials & methods: A noninterventional, cross-sectional, retrospective study design was implemented following a controlled, stratified-by-region, random sampling protocol. The sample was based on birthrates in each region of the island of Puerto Rico, according to the 2004 National Birth Registry. Genomic DNA samples from 100 newborns were obtained from the Puerto Rico Newborn Screening Program in dried-blood spot cards. Genotyping using a physiogenomic array was performed for 332 SNPs from 196 cardiometabolic and neuroendocrine genes. Population structure was examined using a Bayesian clustering approach as well as by allelic dissimilarity as a measure of allele sharing.

Results: The Puerto Rican sample was found to be broadly heterogeneous. We observed three main clusters in the population, which we hypothesize to reflect the historical admixture in the Puerto Rican population from Amerindian, African and European ancestors. We present evidence for this interpretation by comparing allele frequencies for the three clusters with those for the same SNPs available from the International HapMap project for Asian, African and European populations.

Conclusion: Our results demonstrate that population analysis can be performed with a physiogenomic array of cardiometabolic and neuroendocrine genes to facilitate the translation of genome diversity into personalized medicine.

Figure 1. Representative sampling (n = 100) per geographic regions based on percentage of birth at each region around the island of Puerto Rico according to the 2004 National Birth Registry

Colors are employed only to highlight the different municipalities in Puerto Rico.

Figure 2. Population stratification of the Puerto Rico sample as represented by the STRUCTURE version 2.2 triangle plot

The diagram represents 71 samples with complete combinatorial genotype results. Samples between the dashed lines and the respective vertices of the triangle are assigned to a specific cluster, but samples bordering the dashed lines or between the dashed lines and the center are not. The total number of individuals assigned to the three clusters was 53. The cluster-specific assignment subtotals were 21 individuals for cluster 1, ten for cluster 2 and 22 for cluster 3. Some samples overlap in their position in the triangle.

Figure 3. Genetic distance dendrogram for 98 individuals genotyped in the Puerto Rican population sample

(B) Dendrogram of (A), with identical sample identifications, color coded to denote the 53 individuals assigned to one of the three clusters in Figure 2. Cluster 1 samples (n = 21) are depicted in red, cluster 2 samples (n = 10) are depicted in green and cluster 3 samples (n = 22) are depicted in blue. The diagram uses a dashed line to highlight the sectors of the dendrogram with disproportionate representation of samples assigned to a given cluster. The p-values are the results of χ² tests comparing the actual number of cluster 2 samples in sector 1, the number of cluster 3 samples in sector 2 and the number of cluster 1 samples in sector 3 to expected values given a random distribution.

Figure 4. Population dissimilarity between the three clusters (cluster 1, cluster 2, cluster 3) found by STRUCTURE in the Puerto Rico sample of 71 individuals with complete combinatorial genotypes compared with three International HapMap reference populations of different ethnicity (CEU, HCB, YRI)

CEU represents individuals of European descent, HCB represents individuals of Asian origin and YRI represents individuals of sub-Saharan African origin. For each of the reference populations, the y-axis plots the relevant dissimilarity in allele frequency based on RMS matches to the individual clusters. The best matching cluster for each reference population is indicated by a circle. CEU: Northern and Western Europe; HCB: Han Chinese from Beijing; RMS: Root mean square; YRI: Yoruba people from Idaban, Nigeria.

Figure 5. Ancestry contributions calculated using STRUCTURE for each of the 71 individuals from the Puerto Rican sample with complete combinatorial genotypes

Individuals are aligned according to their highest relative contributions of ancestry from cluster 1 (red), samples to the left of diagram; cluster 2 (green), samples to the center; and cluster 3 (blue), samples to the right.