Selecting Closely-Linked SNPs Based on Local Epistatic Effects for Haplotype Construction Improves Power of Association Mapping
Genome-wide association studies (GWAS) have gained central importance for the identification of candidate loci underlying complex traits. Single nucleotide polymorphism (SNP) markers are mostly used as genetic variants for the analysis of genotype-phenotype associations in populations, but closely l...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Oxford University Press
2019-12-01
|
| Series: | G3: Genes, Genomes, Genetics |
| Subjects: | |
| Online Access: | http://g3journal.org/lookup/doi/10.1534/g3.119.400451 |
| _version_ | 1818440172653510656 |
|---|---|
| author | Fang Liu Renate H. Schmidt Jochen C. Reif Yong Jiang |
| author_facet | Fang Liu Renate H. Schmidt Jochen C. Reif Yong Jiang |
| author_sort | Fang Liu |
| collection | DOAJ |
| description | Genome-wide association studies (GWAS) have gained central importance for the identification of candidate loci underlying complex traits. Single nucleotide polymorphism (SNP) markers are mostly used as genetic variants for the analysis of genotype-phenotype associations in populations, but closely linked SNPs that are grouped into haplotypes are also exploited. The benefit of haplotype-based GWAS approaches vs. SNP-based approaches is still under debate because SNPs in high linkage disequilibrium provide redundant information. To overcome some constraints of the commonly-used haplotype-based GWAS in which only consecutive SNPs are considered for haplotype construction, we propose a new method called functional haplotype-based GWAS (FH GWAS). FH GWAS is featured by combining SNPs into haplotypes based on the additive and epistatic effects among SNPs. Such haplotypes were termed functional haplotypes (FH). As shown by simulation studies, the FH GWAS approach clearly outperformed the SNP-based approach unless the minor allele frequency of the SNPs making up the haplotypes is low and the linkage disequilibrium between them is high. Applying FH GWAS for the trait flowering time in a large Arabidopsis thaliana population with whole-genome sequencing data revealed its potential empirically. FH GWAS identified all candidate regions which were detected in SNP-based and two other haplotype-based GWAS approaches. In addition, a novel region on chromosome 4 was solely detected by FH GWAS. Thus both the results of our simulation and empirical studies demonstrate that FH GWAS is a promising method and superior to the SNP-based approach even if almost complete genotype information is available. |
| first_indexed | 2024-12-14T18:08:08Z |
| format | Article |
| id | doaj.art-eb3e4164d47141049827fc5dd8a4d214 |
| institution | Directory Open Access Journal |
| issn | 2160-1836 |
| language | English |
| last_indexed | 2024-12-14T18:08:08Z |
| publishDate | 2019-12-01 |
| publisher | Oxford University Press |
| record_format | Article |
| series | G3: Genes, Genomes, Genetics |
| spelling | doaj.art-eb3e4164d47141049827fc5dd8a4d2142022-12-21T22:52:20ZengOxford University PressG3: Genes, Genomes, Genetics2160-18362019-12-019124115412610.1534/g3.119.40045120Selecting Closely-Linked SNPs Based on Local Epistatic Effects for Haplotype Construction Improves Power of Association MappingFang LiuRenate H. SchmidtJochen C. ReifYong JiangGenome-wide association studies (GWAS) have gained central importance for the identification of candidate loci underlying complex traits. Single nucleotide polymorphism (SNP) markers are mostly used as genetic variants for the analysis of genotype-phenotype associations in populations, but closely linked SNPs that are grouped into haplotypes are also exploited. The benefit of haplotype-based GWAS approaches vs. SNP-based approaches is still under debate because SNPs in high linkage disequilibrium provide redundant information. To overcome some constraints of the commonly-used haplotype-based GWAS in which only consecutive SNPs are considered for haplotype construction, we propose a new method called functional haplotype-based GWAS (FH GWAS). FH GWAS is featured by combining SNPs into haplotypes based on the additive and epistatic effects among SNPs. Such haplotypes were termed functional haplotypes (FH). As shown by simulation studies, the FH GWAS approach clearly outperformed the SNP-based approach unless the minor allele frequency of the SNPs making up the haplotypes is low and the linkage disequilibrium between them is high. Applying FH GWAS for the trait flowering time in a large Arabidopsis thaliana population with whole-genome sequencing data revealed its potential empirically. FH GWAS identified all candidate regions which were detected in SNP-based and two other haplotype-based GWAS approaches. In addition, a novel region on chromosome 4 was solely detected by FH GWAS. Thus both the results of our simulation and empirical studies demonstrate that FH GWAS is a promising method and superior to the SNP-based approach even if almost complete genotype information is available.http://g3journal.org/lookup/doi/10.1534/g3.119.400451haplotypeepistasisgenome-wide association study |
| spellingShingle | Fang Liu Renate H. Schmidt Jochen C. Reif Yong Jiang Selecting Closely-Linked SNPs Based on Local Epistatic Effects for Haplotype Construction Improves Power of Association Mapping G3: Genes, Genomes, Genetics haplotype epistasis genome-wide association study |
| title | Selecting Closely-Linked SNPs Based on Local Epistatic Effects for Haplotype Construction Improves Power of Association Mapping |
| title_full | Selecting Closely-Linked SNPs Based on Local Epistatic Effects for Haplotype Construction Improves Power of Association Mapping |
| title_fullStr | Selecting Closely-Linked SNPs Based on Local Epistatic Effects for Haplotype Construction Improves Power of Association Mapping |
| title_full_unstemmed | Selecting Closely-Linked SNPs Based on Local Epistatic Effects for Haplotype Construction Improves Power of Association Mapping |
| title_short | Selecting Closely-Linked SNPs Based on Local Epistatic Effects for Haplotype Construction Improves Power of Association Mapping |
| title_sort | selecting closely linked snps based on local epistatic effects for haplotype construction improves power of association mapping |
| topic | haplotype epistasis genome-wide association study |
| url | http://g3journal.org/lookup/doi/10.1534/g3.119.400451 |
| work_keys_str_mv | AT fangliu selectingcloselylinkedsnpsbasedonlocalepistaticeffectsforhaplotypeconstructionimprovespowerofassociationmapping AT renatehschmidt selectingcloselylinkedsnpsbasedonlocalepistaticeffectsforhaplotypeconstructionimprovespowerofassociationmapping AT jochencreif selectingcloselylinkedsnpsbasedonlocalepistaticeffectsforhaplotypeconstructionimprovespowerofassociationmapping AT yongjiang selectingcloselylinkedsnpsbasedonlocalepistaticeffectsforhaplotypeconstructionimprovespowerofassociationmapping |