title: Fine-scale population structure of Malays in Peninsular Malaysia and Singapore and implications for association studies.
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.
authors.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.|Institute of Medical Molecular Biotechnology, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Selangor, Malaysia. hoh.boonpeng@gmail.com.|UCSI University, Kuala Lumpur Campus, Cheras, Kuala Lumpur, Malaysia. hoh.boonpeng@gmail.com.
authors.forename: Boon-Peng
authors.initials: BP
authors.lastname: Hoh
authors.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.
authors.forename: Lian
authors.initials: L
authors.lastname: Deng
authors.affiliation: Institute of Medical Molecular Biotechnology, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Selangor, Malaysia.
authors.forename: Mat Jusoh
authors.initials: MJ
authors.lastname: Julia-Ashazila
authors.affiliation: Institute of Medical Molecular Biotechnology, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Selangor, Malaysia.
authors.forename: Zakaria
authors.initials: Z
authors.lastname: Zuraihan
authors.affiliation: Institute of Medical Molecular Biotechnology, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Selangor, Malaysia.
authors.forename: Ma'amor
authors.initials: M
authors.lastname: Nur-Hasnah
authors.affiliation: Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, 16150, Malaysia.
authors.forename: Ab Rajab
authors.initials: AR
authors.lastname: Nur-Shafawati
authors.affiliation: Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, 16150, Malaysia.
authors.forename: Wan Isa
authors.initials: WI
authors.lastname: Hatin
authors.affiliation: Faculty of Science and Technology, School of Biosciences and Biotechnology, Universiti Kebangsaan Malaysia, Bangi, 43600, Malaysia.
authors.forename: Ismail
authors.initials: I
authors.lastname: Endom
authors.affiliation: Department of Pediatrics, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, 16150, Malaysia.
authors.forename: Bin Alwi
authors.initials: BA
authors.lastname: Zilfalil
authors.affiliation: Institute of Medical Molecular Biotechnology, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Selangor, Malaysia.|UCSI University, Jalan Menara Gading, Taman Connaught, 56000, Kuala Lumpur, Wilayah Persekutuan, Malaysia.
authors.forename: Yusoff
authors.initials: Y
authors.lastname: Khalid
authors.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. xushua@picb.ac.cn.|School of Life Science and Technology, ShanghaiTec University, Shanghai, 200031, China. xushua@picb.ac.cn.|Collaborative Innovation Center of Genetics and Development, Shanghai, 200438, China. xushua@picb.ac.cn.
authors.forename: Shuhua
authors.initials: S
authors.lastname: Xu
mesh_terms: D044466:Asian People / Q000235:genetics*; D005828:Genetics, Population; D055106:Genome-Wide Association Study; D006801:Humans; D008296:Malaysia; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012846:Singapore