Exploration of the utility of ancestry informative markers for genetic association studies of African Americans with type 2 diabetes and end stage renal disease
Exploration of the utility of ancestry informative markers for genetic association studies of African Americans with type 2 diabetes and end stage renal disease
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DOI：
10.1007/s00439-008-0532-6
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发表时间：
2008-09-01
期刊：
影响因子：
5.3
通讯作者：
Sale, Michele M.
中科院分区：
文献类型：
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作者：
Keene, Keith L.;Mychaleckyj, Josyf C.;Sale, Michele M.
混合和群体分层是遗传关联研究中的主要问题。我们希望利用非裔美国人（AA）与2型糖尿病（T2DM）和终末期肾病（ESRD）遗传关联研究的经验数据来评估这种混合的影响。对577例患有T2DM-ESRD的AA、596例AA对照、44例尼日利亚约鲁巴（YRI）对照和39例欧美（EA）对照进行了70个祖先信息标记（AIMs）的基因分型。我们纳入了AA人群中8个T2DM候选基因研究的基因型数据和相关结果。使用不同数量的AIMs(25、50和70)，对所有AA样本使用FRAPPE、ADMIXMAP和STRUCTURE计算祖先估计。三个程序的祖先估计值差异很大，使用STRUCTURE获得的估计值最高，其次是ADMIXMAP；而FRAPPE的估计是最低的。使用不同数量目标的FRAPPE估计相似，而使用25个目标的STRUCTURE估计与使用50和70个目标的估计不同。与女性对照组、男性对照组和男性对照组相比，女性T2DM-ESRD病例的平均非洲比例更高。在AA病例中，年龄与个体祖先估计值呈微弱但显著的相关性(r(2) = 0.101；P = 0.019)，在组合集(r(2) = 0.131；P = 3.57 x 10(5))。亲本群体频率之间的绝对差异，即绝对δ，与显性、加性和隐性基因型关联模型的混合影响相关。本研究对掺入物对AA合并T2DM-ESRD研究的影响进行了探索性分析，并支持使用祖先比例作为减少掺入物引起的混杂效应的手段。
Admixture and population stratification are major concerns in genetic association studies. We wished to evaluate the impact of admixture using empirically derived data from genetic association studies of African Americans (AA) with type 2 diabetes (T2DM) and end-stage renal disease (ESRD). Seventy ancestry informative markers (AIMs) were genotyped in 577 AA with T2DM-ESRD, 596 AA controls, 44 Yoruba Nigerian (YRI) and 39 European American (EA) controls. Genotypic data and association results for eight T2DM candidate gene studies in our AA population were included. Ancestral estimates were calculated using FRAPPE, ADMIXMAP and STRUCTURE for all AA samples, using varying numbers of AIMs (25, 50, and 70). Ancestry estimates varied significantly across all three programs with the highest estimates obtained using STRUCTURE, followed by ADMIXMAP; while FRAPPE estimates were the lowest. FRAPPE estimates were similar using varying numbers of AIMs, while STRUCTURE estimates using 25 AIMs differed from estimates using 50 and 70 AIMs. Female T2DM-ESRD cases showed higher mean African proportions as compared to female controls, male cases, and male controls. Age showed a weak but significant correlation with individual ancestral estimates in AA cases (r(2) = 0.101; P = 0.019) and in the combined set (r(2) = 0.131; P = 3.57 x 10(5)). The absolute difference between frequencies in parental populations, absolute delta, was correlated with admixture impact for dominant, additive, and recessive genotypic models of association. This study presents exploratory analyses of the impact of admixture on studies of AA with T2DM-ESRD and supports the use of ancestral proportions as a means of reducing confounding effects due to admixture.