Candidate malaria susceptibility/protective SNPs in hospital and population-based studies: the effect of sub-structuring
Candidate malaria susceptibility/protective SNPs in hospital and population-based studies: the effect of sub-structuring
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DOI：
10.1186/1475-2875-9-119
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发表时间：
2010-05-08
期刊：
影响因子：
3
通讯作者：
Ibrahim, Muntaser E.
中科院分区：
文献类型：
--
作者：
Eid, Nahid A.;Hussein, Aymen A.;Ibrahim, Muntaser E.
背景：包括苏丹在内的东非人口在非洲大陆和世界范围内表现出一些最高的遗传多样性指数。目前的研究旨在解决人口结构和人口分层对不同苏丹人口疟疾候选基因病例对照关联分析结果的可能影响，其中明显的遗传异质性成为对研究结果潜在影响的关注来源。方法：采用Sequenom (R) iPLEX Gold法对449份DNA样本进行72个snp基因分型，包括；来自两个村庄人口的病例和对照、来自Sinnar地区的疟疾患者和门诊患者，以及由讲尼罗-撒哈拉语的健康个体组成的额外对照。使用Structure 2.2程序估算种群子结构。结果与讨论：Hausa和Massalit的Hardy-Weinberg平衡值在预期范围内。然而，在Sinnar地区，纯合性明显过剩，这归因于样本内群体合并产生的鲸鱼效应。节目《结构》揭示了豪萨语和马萨利特语都分为两个子结构，豪萨语的划分比马萨利特语的划分更明显；在Sinnar中没有明确的子结构。在所有地区检测的72个snp中，有超过25个具有信息性。一些重要的snp在疟疾病例和对照之间的分布没有差异，包括CD36和NOS2中的snp。一些snp在病例和对照组之间的基因型分布差异显示显著的P值，包括：医院样本中的rs1805015 (IL4R1) （P = 0.001）、rs17047661 (CR1) （P = 0.02）和rs1800750 (TNF-376)(P = 0.01)；rs1050828 (G6PD+202) （P = 0.02）和rs1800896 (IL10-1082) （P = 0.04）在Massalit和rs2243250 (IL4-589) （P = 0.04）在Hausa。结论：人群结构的差异在一定程度上解释了这些显著关联，并且无论在医院还是基于人群的研究中，关联强度都被证明对各级子结构敏感。
Background: Populations of East Africa including Sudan, exhibit some of the highest indices of genetic diversity in the continent and worldwide. The current study aims to address the possible impact of population structure and population stratification on the outcome of case-control association-analysis of malaria candidate-genes in different Sudanese populations, where the pronounced genetic heterogeneity becomes a source of concern for the potential effect on the studies outcome.Methods: A total of 72 SNPs were genotyped using the Sequenom (R) iPLEX Gold assay in 449 DNA samples that included; cases and controls from two village populations, malaria patients and out-patients from the area of Sinnar and additional controls consisting of healthy Nilo-Saharan speaking individuals. The population substructure was estimated using the Structure 2.2 programme.Results & Discussion: The Hardy-Weinberg Equilibrium values were generally within expectation in Hausa and Massalit. However, in the Sinnar area there was a notable excess of homozygosity, which was attributed to the Whalund effect arising from population amalgamation within the sample. The programme STRUCTURE revealed a division of both Hausa and Massalit into two substructures with the partition in Hausa more pronounced than in Massalit; In Sinnar there was no defined substructure. More than 25 of the 72 SNPs assayed were informative in all areas. Some important SNPs were not differentially distributed between malaria cases and controls, including SNPs in CD36 and NOS2. A number of SNPs showed significant p-values for differences in distribution of genotypes between cases and controls including: rs1805015 (in IL4R1) (P = 0.001), rs17047661 (in CR1) (P = 0.02) and rs1800750 (TNF-376)(P = 0.01) in the hospital samples; rs1050828 (G6PD+202) (P = 0.02) and rs1800896 (IL10-1082) (P = 0.04) in Massalit and rs2243250 (IL4-589) (P = 0.04) in Hausa.Conclusions: The difference in population structure partly accounts for some of these significant associations, and the strength of association proved to be sensitive to all levels of sub-structuring whether in the hospital or population-based study.