Divers Jasmin, Moossavi Shahriar, Langefeld Carl D, Freedman Barry I
Division of Public Health Sciences, Department of Biostatistical Sciences, Section on Statistical Genetics and Bioinformatics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Ethn Dis. 2008 Summer;18(3):384-8.
Diseases with an inherited component that demonstrate different prevalence in various ancestral populations can now be studied using admixture mapping in an appropriate admixed population. This strategy called mapping by admixture linkage disequilibrium or MALD utilizes polymorphic genetic markers that are spaced throughout the genome to identify genomic regions where the estimated admixture proportion is significantly different than its expected value. These genetic markers are selected based on their ancestry informativeness content. The MALD approach assumes that genomic regions showing excess ancestry from the ancestral population with higher disease prevalence, in the sample of admixed individuals, are more likely to harbor polymorphisms that confer higher risk to disease than others. Certain conditions including essential hypertension, type 2 diabetes mellitus and common complex forms of nephropathy demonstrate clear differences in disease frequency in individuals of African and European descent and appear particularly suited to this type of analysis. Genetic admixture can also cause confounding in association studies conducted on an admixed sample leading to inflated type I error rates and possible loss of power. This manuscript describes the background, methodologies and uses for admixture mapping in the search for genes that underlie type 2 diabetes mellitus and its associated nephropathy in the African American population, and statistical methods to address the confounding issues in genetic association tests.
对于具有遗传成分且在不同祖先群体中表现出不同患病率的疾病,现在可以在合适的混合群体中使用混合映射进行研究。这种称为通过混合连锁不平衡映射(MALD)的策略利用遍布基因组的多态性遗传标记来识别估计的混合比例与其预期值显著不同的基因组区域。这些遗传标记是根据其祖先信息含量选择的。MALD方法假定,在混合个体样本中,显示来自疾病患病率较高的祖先群体的祖先过多的基因组区域,比其他区域更有可能含有赋予疾病更高风险的多态性。某些疾病,包括原发性高血压、2型糖尿病和常见的复杂性肾病,在非洲裔和欧洲裔个体中的疾病频率存在明显差异,似乎特别适合这种类型的分析。遗传混合也可能在对混合样本进行的关联研究中造成混淆,导致I型错误率膨胀和可能的效力丧失。本文描述了在非裔美国人中寻找2型糖尿病及其相关肾病潜在基因的混合映射的背景、方法和用途,以及解决基因关联测试中混淆问题的统计方法。