Study Progress on Rare Variants Association Studies and Its Application in Livestock

MIAO Jian;CHANG Tian-peng;SHI Xin-ping;XIA Jiang-wei;GAO Hui-jiang;LI Jun-ya;Institute of Animal Science,Chinese Academy of Agricultural Sciences;College of Animal Science,Fujian Agriculture and Forestry University;

RVAS;;extreme phenotype sample;;meta-analysis;;imputation;;rare haplotype

Genome-wide association studies have identified thousands of associations between common variants and common diseases(traits)in the last decade.Despite these discoveries,the missing heritability has attracted much concerns increasingly.Rare variants have become a key answer to explain the missing heritability,because GWAS focus on identifying the associations between common variants and phenotypes.The rapid advances in DNA sequence have made it possible to identify the associations between rare variants and common diseases(traits).A series of rare variants association analysis(RVAS)methods have been proposed and were applicated to many human diseases,however fewer investigations in livestock.In this review,we first briefly report the methods of sequence kernel association test(SKAT)and its family,which are representative.Then,we summary two methods which are used to improve the effectiveness in RVAS:extreme phenotype sampling and meta-analysis.Hereafter,we review the methods utilizing GWAS data to perform RVAS:imputation and rare haplotype associations analysis.Finally,we provide some guidelines for performing RVAS in livestock.