Extending admixture mapping to nuclear pedigrees: application to sarcoidosis.
Extending admixture mapping to nuclear pedigrees: application to sarcoidosis.
复制标题
DOI：
10.1002/gepi.21710
复制
发表时间：
2013-04
影响因子：
2.1
通讯作者：
Rybicki, Benjamin A.
中科院分区：
文献类型：
--
作者：
McKeigue, Paul M.;Colombo, Marco;Agakov, Felix;Datta, Indrani;Levin, Albert;Favro, David;Gray-Montgomery, Courtney;Iannuzzi, Michael C.;Rybicki, Benjamin A.
我们描述了统计方法，扩展了从不相关个体到核谱系的混合映射的应用，允许现有的基于谱系的集合得到充分利用。通过开发一种利用祖先转换底层模型的阶乘结构的快速算法，克服了计算方面的挑战。这是作为程序ADMIXMAP的扩展实现的。我们展示了该方法在非裔美国人结节病研究中的应用，该研究以前仅作为一种限制于不相关个体的混合作图研究进行分析。虽然在谱系分析中检测到的祖先信号通常与在早期不相关病例的分析中检测到的信号相似，但我们能够提取更多信息，从而产生更清晰的排除图；使用LOD得分为- 2的经典标准，谱系分析能够排除与96%以上的非洲血统相关的风险比为2或更多，而在早期的分析中，只有83%的非亲属个体。虽然ADMIXMAP的谱系扩展只能在相对较低的密度下使用祖先信息标记，但它可以使用来自WINPOP或HAPMIX等程序的输入祖先状态，这些程序使用密集的SNP标记基因型进行混合定位。这提高了这种强大的基因定位方法的效率和应用范围。
We describe statistical methods that extend the application of admixture mapping from unrelated individuals to nuclear pedigrees, allowing existing pedigree-based collections to be fully exploited. Computational challenges have been overcome by developing a fast algorithm that exploits the factorial structure of the underlying model of ancestry transitions. This has been implemented as an extension of the program ADMIXMAP. We demonstrate the application of the method to a study of sarcoidosis in African Americans that has previously been analyzed only as an admixture mapping study restricted to unrelated individuals. Although the ancestry signals detected in this pedigree analysis are generally similar to those detected in the earlier analysis of unrelated cases, we are able to extract more information and this yields a much sharper exclusion map; using the classical criterion of an LOD score of minus 2, the pedigree analysis is able to exclude a risk ratio of 2 or more associated with African ancestry over 96% of the genome, compared with only 83% in the earlier analysis of unrelated individuals only. Although the pedigree extension of ADMIXMAP can use ancestry-informative markers only at relatively low density, it can use imputed ancestry states from programs such as WINPOP or HAPMIX that use dense SNP marker genotypes for admixture mapping. This extends both the efficiency and the range of application of this powerful gene mapping method.
登录
查看更多内容
影响因子：
5.3
作者：
Lind, Joanne M.;Hutcheson-Dilks, Holli B.;Smith, Michael W.
通讯作者：
Smith, Michael W.
DOI：
10.1164/ajrccm.164.11.2106001
发表时间：
2001-12-01
影响因子：
24.7
作者：
Rybicki, BA;Iannuzzi, MC;Cherniack, R
通讯作者：
Cherniack, R
影响因子：
4.5
作者：
Pasaniuc B;Zaitlen N;Lettre G;Chen GK;Tandon A;Kao WH;Ruczinski I;Fornage M;Siscovick DS;Zhu X;Larkin E;Lange LA;Cupples LA;Yang Q;Akylbekova EL;Musani SK;Divers J;Mychaleckyj J;Li M;Papanicolaou GJ;Millikan RC;Ambrosone CB;John EM;Bernstein L;Zheng W;Hu JJ;Ziegler RG;Nyante SJ;Bandera EV;Ingles SA;Press MF;Chanock SJ;Deming SL;Rodriguez-Gil JL;Palmer CD;Buxbaum S;Ekunwe L;Hirschhorn JN;Henderson BE;Myers S;Haiman CA;Reich D;Patterson N;Wilson JG;Price AL
通讯作者：
Price AL
影响因子：
9.8
作者：
Parra, EJ;Marcini, A;Shriver, MD
通讯作者：
Shriver, MD
DOI：
10.1016/0007-0971(85)90004-x
发表时间：
1985-01-01
期刊：
BRITISH JOURNAL OF DISEASES OF THE CHEST
影响因子：
--
作者：
EDMONDSTONE, WM;WILSON, AG
通讯作者：
WILSON, AG