A first trial of retrospective collaboration for positional cloning in complex inheritance: Assay of the cytokine region on chromosome 5 by the Consortium on Asthma Genetics (COAG)

被引:37
作者
Lonjou, C
Barnes, K
Chen, H
Cookson, WOCM
Deichmann, KA
Hall, IP
Holloway, JW
Laitinen, T
Palmer, LJ
Wjst, M
Morton, NE [1 ]
机构
[1] Univ Southampton, Southampton Gen Hosp, Human Genet Res Div, Southampton SO16 6YD, Hants, England
[2] Johns Hopkins Univ, Baltimore, MD 21224 USA
[3] Chinese Acad Med Sci, Inst Basic Med Sci, Dept Mol Biol, Beijing 100005, Peoples R China
[4] John Radcliffe Hosp, Nuffield Dept Clin Med, Asthma Genet Grp, Oxford OX3 9DU, England
[5] Univ Freiburg, Childrens Hosp, D-79106 Freiburg, Germany
[6] Univ Nottingham Hosp, Dept Med, Div Therapeut, Nottingham NG7 2UH, England
[7] Southampton Gen Hosp, Human Genet Res Div, Asthma Genet Grp, Southampton SO16 6YD, Hants, England
[8] Univ Helsinki, Dept Med Genet, Helsinki 00014, Finland
[9] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA
[10] Harvard Univ, Sch Med, Boston, MA 02115 USA
[11] GSF, Natl Res Ctr Environm & Hlth, Inst Epidemiol, D-85758 Neuherberg, Germany
关键词
D O I
10.1073/pnas.97.20.10942
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The central problem of complex inheritance is to map oligogenes for disease susceptibility, integrating linkage and association over samples that differ in several ways. Combination of evidence over multiple samples with 1,037 families supports loci contributing to asthma susceptibility in the cytokine region on 5q [maximum logarithm of odds (lod) = 2.61 near IL-4], but no evidence for atopy. The principal problems with retrospective collaboration on linkage appear to have been solved, providing far more information than a single study. A multipoint lod table evaluated at commonly agreed reference loci is required for both collaboration and metaanalysis, but variations in ascertainment, pedigree structure, phenotype definition, and marker selection are tolerated. These methods are invariant with statistical methods that increase the power of lods and are applicable to all diseases, motivating collaboration rather than competition. In contrast to linkage, positional cloning by allelic association has yet to be extended to multiple samples, a prerequisite for efficient combination with linkage and the greatest current challenge to genetic epidemiology.
引用
收藏
页码:10942 / 10947
页数:6
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