Prioritized candidate causal haplotype blocks in plant genome-wide association studies

Xing Wu, Wei Jiang, Christopher Fragoso, Jing Huang, Geyu Zhou, Hongyu Zhao and Stephen Dellaporta

PLOS Genetics, 2022, vol. 18, issue 10, 1-25

Abstract: Genome wide association studies (GWAS) can play an essential role in understanding genetic basis of complex traits in plants and animals. Conventional SNP-based linear mixed models (LMM) that marginally test single nucleotide polymorphisms (SNPs) have successfully identified many loci with major and minor effects in many GWAS. In plant, the relatively small population size in GWAS and the high genetic diversity found in many plant species can impede mapping efforts on complex traits. Here we present a novel haplotype-based trait fine-mapping framework, HapFM, to supplement current GWAS methods. HapFM uses genotype data to partition the genome into haplotype blocks, identifies haplotype clusters within each block, and then performs genome-wide haplotype fine-mapping to prioritize the candidate causal haplotype blocks of trait. We benchmarked HapFM, GEMMA, BSLMM, GMMAT, and BLINK in both simulated and real plant GWAS datasets. HapFM consistently resulted in higher mapping power than the other GWAS methods in high polygenicity simulation setting. Moreover, it resulted in smaller mapping intervals, especially in regions of high LD, achieved by prioritizing small candidate causal blocks in the larger haplotype blocks. In the Arabidopsis flowering time (FT10) datasets, HapFM identified four novel loci compared to GEMMA’s results, and the average mapping interval of HapFM was 9.6 times smaller than that of GEMMA. In conclusion, HapFM is tailored for plant GWAS to result in high mapping power on complex traits and improved on mapping resolution to facilitate crop improvement.Author summary: Genome-wide association studies (GWAS) are commonly used in human and plant studies to identify genetic variants responsible for the phenotype of interest and provide foundations for studying disease mechanisms and crop improvement. Most GWAS models are developed and optimized using human datasets. However, the difference between human and plant datasets essentially limits their applications in plant studies, especially when mapping complex traits such as drought resistance and yield. In this study, we present a novel GWAS method, HapFM, tailored for plant datasets to overcome the difficulties of many conventional GWAS methods. HapFM resulted in higher statistical power than conventional GWAS methods for mapping complex traits in our simulation and real dataset analyses. In addition, HapFM reduced the mapping interval by prioritizing candidate causal regions in the genome, which benefits the downstream experimental studies. Last but not least, HapFM can incorporate biological annotations to increase statistical power further. Overall, HapFM balances statistical power, result interpretability, and downstream experimental verifiability.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pgen00:1010437

DOI: 10.1371/journal.pgen.1010437

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