Improving power and accuracy of genome-wide association studies via a multi-locus mixed linear model methodology

Scientific Reports
Shi-Bo WangYuan-Ming Zhang

Abstract

Genome-wide association studies (GWAS) have been widely used in genetic dissection of complex traits. However, common methods are all based on a fixed-SNP-effect mixed linear model (MLM) and single marker analysis, such as efficient mixed model analysis (EMMA). These methods require Bonferroni correction for multiple tests, which often is too conservative when the number of markers is extremely large. To address this concern, we proposed a random-SNP-effect MLM (RMLM) and a multi-locus RMLM (MRMLM) for GWAS. The RMLM simply treats the SNP-effect as random, but it allows a modified Bonferroni correction to be used to calculate the threshold p value for significance tests. The MRMLM is a multi-locus model including markers selected from the RMLM method with a less stringent selection criterion. Due to the multi-locus nature, no multiple test correction is needed. Simulation studies show that the MRMLM is more powerful in QTN detection and more accurate in QTN effect estimation than the RMLM, which in turn is more powerful and accurate than the EMMA. To demonstrate the new methods, we analyzed six flowering time related traits in Arabidopsis thaliana and detected more genes than previous reported using the EMMA. Therefore, the MRM...Continue Reading

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Citations

Oct 24, 2017·Asian-Australasian Journal of Animal Sciences·Jianping QuanJie Yang
Sep 16, 2018·Respirology : Official Journal of the Asian Pacific Society of Respirology·Bhavna HurgobinAnthony Bosco
May 31, 2019·Journal of Experimental Botany·Gopal MisraNese Sreenivasulu
Oct 24, 2019·Heredity·Bingxing AnHuijiang Gao
Feb 29, 2020·International Journal of Molecular Sciences·Samuel LanFrank M You
Jul 28, 2018·Plant Molecular Biology·Jing ZhouMeng-Zhu Lu
Jan 22, 2019·Frontiers in Plant Science·Mingwei GuanCunmin Qu
Dec 14, 2018·Frontiers in Plant Science·Xin HuDongfa Sun
Jan 19, 2019·International Journal of Molecular Sciences·Liqiang HeFrank M You
Dec 12, 2017·Heredity·Julong WeiZhenyu Jia

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Methods Mentioned

BETA
dissection

Software Mentioned

Net
EMMA
R
minPtest R package
Elastic

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