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Fine-scale population structure of Malays in Peninsular Malaysia and Singapore and implications for association studies.

Hoh BP, Deng L, Julia-Ashazila MJ, Zuraihan Z, Nur-Hasnah M, Nur-Shafawati AR, Hatin WI, Endom I, Zilfalil BA, Khalid Y, Xu S - Hum. Genomics (2015)

Bottom Line: On an even finer scale, the genetic coordinates of the geographical Malay populations are in correlation with the latitudes (R(2) = 0.3925; P = 0.029).The collective findings therefore suggest that population sub-structure of Malays are more heterogenous than previously expected even within a small geographical region, possibly due to factors like different genetic origins, geographical isolation, could result in spurious association as demonstrated in our analysis.We suggest that cautions should be taken during the stage of study design or interpreting the association signals in disease mapping studies which are expected to be conducted in Malay population in the near future.

View Article: PubMed Central - PubMed

Affiliation: Chinese Academy of Sciences (CAS) Key Laboratory of Computational Biology, Max Planck Independent Research Group on Population Genomics, CAS-MPG Partner Institute for Computational Biology (PICB), Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China. hoh.boonpeng@gmail.com.

ABSTRACT
Fine scale population structure of Malays - the major population in Malaysia, has not been well studied. This may have important implications for both evolutionary and medical studies. Here, we investigated the population sub-structure of Malay involving 431 samples collected from all states from peninsular Malaysia and Singapore. We identified two major clusters of individuals corresponding to the north and south peninsular Malaysia. On an even finer scale, the genetic coordinates of the geographical Malay populations are in correlation with the latitudes (R(2) = 0.3925; P = 0.029). This finding is further supported by the pairwise FST of Malay sub-populations, of which the north and south regions showed the highest differentiation (FST [North-south] = 0.0011). The collective findings therefore suggest that population sub-structure of Malays are more heterogenous than previously expected even within a small geographical region, possibly due to factors like different genetic origins, geographical isolation, could result in spurious association as demonstrated in our analysis. We suggest that cautions should be taken during the stage of study design or interpreting the association signals in disease mapping studies which are expected to be conducted in Malay population in the near future.

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Correlation between PC1 and latitude coordinate (P = 0.029)
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Fig4: Correlation between PC1 and latitude coordinate (P = 0.029)

Mentions: Given the fact that the PC1 as well as the ADMIXTURE analysis showed significant differences between northern and southern Malay samples, we then investigated if the genetic diversity between these sub-structure of Malays in Peninsular Malaysia were attributed to geographical coordinates. Average PC1 values of southern Malay samples (corresponding to Fig. 1b) were generally less than 0 (except for Johor), whilst all geographically defined northern regions with PC1 >0 (Fig. 3). When we compared the PC1 with geographical latitude of these sample locations, a significant correlation was observed (R2 = 0.3925; P = 0.029; Fig. 4). Due to the geographical nature, Peninsular Malaysia is divided into west coast and east coast by the Titiwangsa Ranges. We therefore asked if the genetic diversity could be attributed to the geographical longitude as well. Analysis between PC1 and geographical longitude, however showed no significant correlation (R2=0.0066; P = 0.7924; Addional file 1: Figure S2). We also evaluated if the genetic diversity was related to geographical distance between two populations, but found no significant correlation of FST between populations and the geographical distances between them (R2 = 0.01918; P = 0.1385; Additional file 1: Figure S3).Fig. 3


Fine-scale population structure of Malays in Peninsular Malaysia and Singapore and implications for association studies.

Hoh BP, Deng L, Julia-Ashazila MJ, Zuraihan Z, Nur-Hasnah M, Nur-Shafawati AR, Hatin WI, Endom I, Zilfalil BA, Khalid Y, Xu S - Hum. Genomics (2015)

Correlation between PC1 and latitude coordinate (P = 0.029)
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4509480&req=5

Fig4: Correlation between PC1 and latitude coordinate (P = 0.029)
Mentions: Given the fact that the PC1 as well as the ADMIXTURE analysis showed significant differences between northern and southern Malay samples, we then investigated if the genetic diversity between these sub-structure of Malays in Peninsular Malaysia were attributed to geographical coordinates. Average PC1 values of southern Malay samples (corresponding to Fig. 1b) were generally less than 0 (except for Johor), whilst all geographically defined northern regions with PC1 >0 (Fig. 3). When we compared the PC1 with geographical latitude of these sample locations, a significant correlation was observed (R2 = 0.3925; P = 0.029; Fig. 4). Due to the geographical nature, Peninsular Malaysia is divided into west coast and east coast by the Titiwangsa Ranges. We therefore asked if the genetic diversity could be attributed to the geographical longitude as well. Analysis between PC1 and geographical longitude, however showed no significant correlation (R2=0.0066; P = 0.7924; Addional file 1: Figure S2). We also evaluated if the genetic diversity was related to geographical distance between two populations, but found no significant correlation of FST between populations and the geographical distances between them (R2 = 0.01918; P = 0.1385; Additional file 1: Figure S3).Fig. 3

Bottom Line: On an even finer scale, the genetic coordinates of the geographical Malay populations are in correlation with the latitudes (R(2) = 0.3925; P = 0.029).The collective findings therefore suggest that population sub-structure of Malays are more heterogenous than previously expected even within a small geographical region, possibly due to factors like different genetic origins, geographical isolation, could result in spurious association as demonstrated in our analysis.We suggest that cautions should be taken during the stage of study design or interpreting the association signals in disease mapping studies which are expected to be conducted in Malay population in the near future.

View Article: PubMed Central - PubMed

Affiliation: Chinese Academy of Sciences (CAS) Key Laboratory of Computational Biology, Max Planck Independent Research Group on Population Genomics, CAS-MPG Partner Institute for Computational Biology (PICB), Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China. hoh.boonpeng@gmail.com.

ABSTRACT
Fine scale population structure of Malays - the major population in Malaysia, has not been well studied. This may have important implications for both evolutionary and medical studies. Here, we investigated the population sub-structure of Malay involving 431 samples collected from all states from peninsular Malaysia and Singapore. We identified two major clusters of individuals corresponding to the north and south peninsular Malaysia. On an even finer scale, the genetic coordinates of the geographical Malay populations are in correlation with the latitudes (R(2) = 0.3925; P = 0.029). This finding is further supported by the pairwise FST of Malay sub-populations, of which the north and south regions showed the highest differentiation (FST [North-south] = 0.0011). The collective findings therefore suggest that population sub-structure of Malays are more heterogenous than previously expected even within a small geographical region, possibly due to factors like different genetic origins, geographical isolation, could result in spurious association as demonstrated in our analysis. We suggest that cautions should be taken during the stage of study design or interpreting the association signals in disease mapping studies which are expected to be conducted in Malay population in the near future.

Show MeSH
Related in: MedlinePlus