Joint analysis of tightly linked SNPs in screening step of genome-wide association studies leads to increased power

被引：17

作者：

Becker, Tim ^{[1
]}

Herold, Christine ^{[1
]}

机构：

[1] Univ Bonn, Inst Med Biometry Informat & Epidemiol, D-53105 Bonn, Germany

来源：

EUROPEAN JOURNAL OF HUMAN GENETICS | 2009年 / 17卷 / 08期

关键词：

genome-wide association studies; haplotypes; literature study; COMMON SEQUENCE VARIANTS; CANCER SUSCEPTIBILITY LOCUS; COLORECTAL-CANCER; PROSTATE-CANCER; CONFER SUSCEPTIBILITY; LUNG-CANCER; RISK LOCI; RHEUMATOID-ARTHRITIS; GENETIC-DETERMINANTS; HAPLOTYPE ANALYSIS;

D O I：

10.1038/ejhg.2009.7

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Recent developments in genome-wide association studies ( GWAS) have lead to the localization of disease genes for many complex diseases. The scrutiny of the respective publications reveals, first, that statistical analysis is restricted typically to single-marker analysis in the first step, and that, second, the presence of multiple, independently associated SNPs within the same linkage disequilibrium ( LD) region is a common phenomenon. Motivated by this observation, we show through a power simulation study that a simultaneous analysis of tightly linked SNPs in the initial GWAS analysis step would lead to increased power, when compared with that in single-marker analysis. This is true for all the three approaches we considered ( implementations in BEAGLE, FAMHAP and UNPHASED). The best performance was obtained using a two-marker haplotype analysis. In conclusion, we would expect additional gene findings for re-analyzing successful GWAS with a multi-marker approach. European Journal of Human Genetics ( 2009) 17, 1043-1049; doi:10.1038/ejhg.2009.7; published online 18 February 2009

引用

页码：1043 / 1049

页数：7

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