BMC Genetics BioMed Central Research article Open Access Genetic structure in four West African population groups Adebowale A Adeyemo*1,2, Guanjie Chen2, Yuanxiu Chen2 and Charles Rotimi2 Address: 1College of Medicine, University of Ibadan, Ibadan. Nigeria and 2National Human Genome Center, Howard University, Washington DC, USA Email: Adebowale A Adeyemo* - [email protected]; Guanjie Chen - [email protected]; Yuanxiu Chen - [email protected]; Charles Rotimi - [email protected] * Corresponding author Published: 24 June 2005 Received: 01 December 2004 Accepted: 24 June 2005 BMC Genetics 2005, 6:38 doi:10.1186/1471-2156-6-38 This article is available from: http://www.biomedcentral.com/1471-2156/6/38 © 2005 Adeyemo et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: Africa contains the most genetically divergent group of continental populations and several studies have reported that African populations show a high degree of population stratification. In this regard, it is important to investigate the potential for population genetic structure or stratification in genetic epidemiology studies involving multiple African populations. The presences of genetic sub-structure, if not properly accounted for, have been reported to lead to spurious association between a putative risk allele and a disease. Within the context of the Africa America Diabetes Mellitus (AADM) Study (a genetic epidemiologic study of type 2 diabetes mellitus in West Africa), we have investigated population structure or stratification in four ethnic groups in two countries (Akan and Gaa-Adangbe from Ghana, Yoruba and Igbo from Nigeria) using data from 372 autosomal microsatellite loci typed in 493 unrelated persons (986 chromosomes). Results: There was no significant population genetic structure in the overall sample. The smallest probability is associated with an inferred cluster of 1 and little of the posterior probability is associated with a higher number of inferred clusters. The distribution of members of the sample to inferred clusters is consistent with this finding; roughly the same proportion of individuals from each group is assigned to each cluster with little variation between the ethnic groups. Analysis of molecular variance (AMOVA) showed that the between-population component of genetic variance is less than 0.1% in contrast to 99.91% for the within population component. Pair-wise genetic distances between the four ethnic groups were also very similar. Nonetheless, the small between- population genetic variance was sufficient to distinguish the two Ghanaian groups from the two Nigerian groups. Conclusion: There was little evidence for significant population substructure in the four major West African ethnic groups represented in the AADM study sample. Ethnicity apparently did not introduce differential allele frequencies that may affect analysis and interpretation of linkage and association studies. These findings, although not entirely surprising given the geographical proximity of these groups, provide important insights into the genetic relationships between the ethnic groups studied and confirm previous results that showed close genetic relationship between most studied West African groups. Page 1 of 9 (page number not for citation purposes) BMC Genetics 2005, 6:38 http://www.biomedcentral.com/1471-2156/6/38 Background our findings to reported ethnic grouping. Next, we used Africa is inhabited by populations that show high levels of analysis of molecular variance (AMOVA) models on the genetic diversity compared to most other continental pop- same data. Finally, we estimate FST and allele sharing dis- ulations today and it is thought to be the ancestral home tances between all population pairs. of modern humans. African populations have the largest number of population specific autosomal, X-chromo- Results somal and mitochondrial DNA haplotypes with non-Afri- The estimates of the logarithms of the probability of the can populations having only a subset of the genetic data under the models and assumptions regarding inde- diversity present in Africa [1]. Estimates of FST (the classic pendence of allele frequencies are shown in Table 1. measure of population subdivision) from mitochondrial Under the admixture model, the smallest probability is DNA are much higher in Africa than other populations, as associated with a prior K of 1 and little of the posterior summarized by Tishkoff et al [1]. In addition, analyses probability is associated with higher K values. The distri- from studies based on autosomal SNPs, STRPs or Alu ele- bution of members of the sample to inferred clusters is ments show higher FST values for African populations [2- consistent with this observation. The proportion of indi- 4]. Recent studies of world populations based on large viduals assigned to each cluster is approximately the same genomic data also reported significant population struc- with little variation between ethnic groups (Table 2). This ture among the African groups [5,6]. However, given the symmetry is strongly suggestive of the absence of popula- cultural and linguistic diversity of African populations tion structure in the AADM study sample. This is so (with over 2000 distinct ethnic groups and languages), because real population structure is associated with indi- these studies have typically included only a handful of viduals being strongly assigned to one inferred cluster or African populations indicating that most African popula- another with the proportions assigned to each ethnic tions have not been studied. As previously noted, most group showing asymmetry. The posterior probability existing genetic data on African populations have come under the no-admixture model also favours a K of 1. from a few countries that are relatively economically Examination of the distribution of individuals sampled to developed and/or with key research or medical centers inferred clusters also shows the same strong symmetry. [1]. Availability of more genetic data from sub Saharan These consistent displays of symmetry suggest that a K of Africa will clearly be useful in our understanding of pop- 1 is the most parsimonious model. The same conclusion ulation structure, demographic history and the efforts to was reached by examining the membership coefficients map disease-causing genes. (Q). Irrespective of the value of K between the range of 2 and 6, Q is similar across the whole sample as illustrated Several genetic epidemiologic studies mapping complex by the bar plots in Figure 2. disease-causing genes have been designed to take advan- tage of the population genetic characteristics of contem- Analysis of molecular variance (AMOVA) shows that most porary African populations for fine mapping of of the variance in the sample is attributable to within-eth- informative genomic regions. These characteristics nic group variation (99.91% of the variance) and between- include lower linkage disequilibrium values [5-9] and ethnic group variation is only 0.09% (Table 3). Locus-by- smaller haplotype block sizes [10,11]. On the other hand, locus AMOVA shows that this pattern of partitioning of African populations have more divergent patterns of LD the variance between within-population and between- and more complex pattern of population substructure or population variation is consistent across all loci and can stratification [12-17]. Population stratification refers to be observed on single locus analysis [see Additional file differences in allele frequencies between cases and con- 2]. An AMOVA model that includes "country" as well as trols due to systematic differences in ancestry rather than "ethnic group" in the model shows that the variance association of genes with disease and it can have a major attributable to between-country variation was 0.13%, that impact on the ability of genetic epidemiologic studies to due to between-ethnic group variation was 0.01% and that detect valid associations between a putative risk allele and due to within-ethnic group variation was 99.86% (Table 3). a disease or trait. The between-country genetic variance in this model was sig- nificant, suggesting that the two groups from one country We investigated population structure or stratification in can be distinguished from the groups from the other four ethnic groups in two countries in West Africa (Akan country. and Gaa-Adangbe from Ghana, Yoruba and Igbo from Nigeria) using data from 372 autosomal microsatellite Pair-wise genetic distance measures show that there is lit- loci [see Additional file 1] typed in 493 unrelated persons tle difference between the four ethnic groups (Table 4). (986 chromosomes). Firstly, we used a clustering algo- The fact that all calculated pair-wise FST values were low rithm to infer population structure in the whole sample suggests little evidence for genetic differentiation between while ignoring ethnic group information and compare the ethnic groups. The fixation index for the entire sample Page 2 of 9 (page number not for citation purposes) BMC Genetics 2005, 6:38 http://www.biomedcentral.com/1471-2156/6/38 K=2 K=3 K=4 K=5 K=6 BarFigure plots 2 of estimates of membership coefficient (Q) for each individual by ethnic group Bar plots of estimates of membership