SNP and Haplotype Regional Heritability Mapping (SNHap-RHM): Joint Mapping of Common and Rare Variation Affecting Complex Traits.
MDD
genome-wide analysis
haplotypes
height
missing heritability
rare variation
regional heritability mapping
Journal
Frontiers in genetics
ISSN: 1664-8021
Titre abrégé: Front Genet
Pays: Switzerland
ID NLM: 101560621
Informations de publication
Date de publication:
2021
2021
Historique:
received:
08
10
2021
accepted:
14
12
2021
entrez:
24
1
2022
pubmed:
25
1
2022
medline:
25
1
2022
Statut:
epublish
Résumé
We describe a genome-wide analytical approach, SNP and Haplotype Regional Heritability Mapping (SNHap-RHM), that provides regional estimates of the heritability across locally defined regions in the genome. This approach utilises relationship matrices that are based on sharing of SNP and haplotype alleles at local haplotype blocks delimited by recombination boundaries in the genome. We implemented the approach on simulated data and show that the haplotype-based regional GRMs capture variation that is complementary to that captured by SNP-based regional GRMs, and thus justifying the fitting of the two GRMs jointly in a single analysis (SNHap-RHM). SNHap-RHM captures regions in the genome contributing to the phenotypic variation that existing genome-wide analysis methods may fail to capture. We further demonstrate that there are real benefits to be gained from this approach by applying it to real data from about 20,000 individuals from the Generation Scotland: Scottish Family Health Study. We analysed height and major depressive disorder (MDD). We identified seven genomic regions that are genome-wide significant for height, and three regions significant at a suggestive threshold (
Identifiants
pubmed: 35069690
doi: 10.3389/fgene.2021.791712
pii: 791712
pmc: PMC8770330
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
791712Subventions
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/J002844/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_U127592696
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00007/10
Pays : United Kingdom
Informations de copyright
Copyright © 2022 Oppong, Boutin, Campbell, McIntosh, Porteous, Hayward, Haley, Navarro and Knott.
Déclaration de conflit d'intérêts
AM has received research support from Eli Lilly and Company, Janssen and the Sackler Trust and speaker fees from Illumina and Janssen. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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