Linkage analysis of adult height in a large pedigree from a Dutch genetically isolated population

被引:10
|
作者
Axenovich, Tatiana I. [1 ,2 ]
Zorkoltseva, I. V. [1 ]
Belonogova, N. M. [1 ,2 ]
Struchalin, M. V. [3 ,4 ]
Kirichenko, A. V. [1 ]
Kayser, M. [3 ]
Oostra, B. A. [4 ]
van Duijn, C. M. [4 ]
Aulchenko, Y. S. [1 ,4 ]
机构
[1] Russian Acad Sci, Inst Cytol & Genet SD, Novosibirsk 630090, Russia
[2] Novosibirsk State Univ, Dept Cytol & Genet, Novosibirsk 630090, Russia
[3] Erasmus Univ, Med Ctr Rotterdam, Dept Forens Mol Biol, NL-3000 CA Rotterdam, Netherlands
[4] Erasmus Univ, Med Ctr Rotterdam, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands
基金
俄罗斯基础研究基金会;
关键词
GENOME-WIDE ASSOCIATION; QUANTITATIVE-TRAIT-LOCUS; BODY-MASS INDEX; BREAST-CANCER; MIXED-MODEL; LIKELIHOOD APPROXIMATION; ALTERNATIVE FORMULATION; COMPLEX SEGREGATION; SMOKING-CESSATION; GROWTH-FACTOR;
D O I
10.1007/s00439-009-0686-x
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Despite extensive research of genetic determinants of human adult height, the genes identified up until now allow to predict only a small proportion of the trait's variance. To identify new genes we analyzed 2,486 genotyped and phenotyped individuals in a large pedigree including 23,612 members in 18 generations. The pedigree was derived from a young genetically isolated Dutch population, where genetic heterogeneity is expected to be low and linkage disequilibrium has been shown to be increased. Complex segregation analysis confirmed high heritability of adult height, and suggested mixed model of height inheritance in this population. The estimates of the model parameters obtained from complex segregation analysis were used in parametric linkage analysis, which highlighted three genome-wide significant and additionally at least four suggestive loci involved in height. Significant peaks were located at the chromosomal regions 1p32 (LOD score = 3.35), 2p16 (LOD score = 3.29) and 16q24 (LOD score = 3.94). For the latter region, a strong association signal (FDR q < 0.05) was obtained for 19 SNPs, 17 of them were located in the CDH13 (cadherin 13) gene of which one (rs1035569) explained 1.5% of the total height variance.
引用
收藏
页码:457 / 471
页数:15
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