a strategy analysis for genetic association studies with known inbreeding战略分析与已知的近亲繁殖遗传关联研究.pdfVIP

Cabras et al. BMC Genetics 2011, 12:63 /1471-2156/12/63 METHODOLOGY ARTICLE Open Access A strategy analysis for genetic association studies with known inbreeding 1* 2 5 3 4 3 Stefano Cabras , Maria Eugenia Castellanos , Ginevra Biino , Ivana Persico , Alessandro Sassu , Laura Casula , 6 1 3,4 4,7 Stefano del Giacco , Francesco Bertolino , Mario Pirastu and Nicola Pirastu Abstract Background: Association studies consist in identifying the genetic variants which are related to a specific disease through the use of statistical multiple hypothesis testing or segregation analysis in pedigrees. This type of studies has been very successful in the case of Mendelian monogenic disorders while it has been less successful in identifying genetic variants related to complex diseases where the insurgence depends on the interactions between different genes and the environment. The current technology allows to genotype more than a million of markers and this number has been rapidly increasing in the last years with the imputation based on templates sets and whole genome sequencing. This type of data introduces a great amount of noise in the statistical analysis and usually requires a great number of samples. Current methods seldom take into account gene-gene and gene-environment interactions which are fundamental especially in complex diseases. In this paper we propose to use a non-parametric additive model to detect the genetic variants related to diseases which accounts for interactions of unknown order. Although this is not new to the current literature, we show that in an isolated population, where