| Title: |
SURFBAT : A surrogate family based association test building on large imputation reference panels |
| Authors: |
FrEx Consortium; FranceGenRef Consortium; Herzig, Anthony F.; Rubinacci, Simone; Marenne, Gaëlle; Génin, Emmanuelle |
| Contributors: |
Institute for Molecular Medicine Finland; University of Helsinki |
| Publisher Information: |
Genetics Society of America |
| Publication Year: |
2025 |
| Collection: |
Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto |
| Subject Terms: |
fine-structure; imputation; local ancestry; population stratification; shared controls; reference panel; Biomedicine; Genetics; developmental biology; physiology |
| Description: |
Genotype–phenotype association tests are typically adjusted for population stratification using principal components that are estimated genome-wide. This lacks resolution when analyzing populations with fine structure and/or individuals with fine levels of admixture. This can affect power and precision, and is a particularly relevant consideration when control individuals are recruited using geographic selection criteria. Such is the case in France where we have recently created reference panels of individuals anchored to different geographic regions. To make correct comparisons against case groups, who would likely be gathered from large urban areas, new methods are needed. We present SURFBAT (a surrogate family based association test), which performs an approximation of the transmission-disequilibrium test. Our method hinges on the application of genotype imputation algorithms to match similar haplotypes between the case and control groups. This permits us to approximate local ancestry informed posterior probabilities of un-transmitted parental alleles of each case individual. This is achieved by assuming haplotypes from the imputation panel are well-matched for ancestry with the case individuals. When the first haplotype of an individual from the imputation panel matches that of a case individual, it is assumed that the second haplotype of the same reference individual can be used as a locally ancestry matched control haplotype and to approximately impute un-transmitted parental alleles. SURFBAT provides an association test that is inherently robust to fine-scale population stratification and opens up the possibility of efficiently using large imputation reference panels as control groups for association testing. In contrast to other methods for association testing that incorporate local-ancestry inference, SURFBAT does not require a set of ancestry groups to be defined, nor for local ancestry to be explicitly estimated. We demonstrate the interest of our tool on simulated datasets, as well as on a real-data ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISBN: |
978-0-01-380016-3; 0-01-380016-7 |
| Relation: |
This work was supported by LABEX GENMED, funded as part of \u201CInvestissement d\u2019avenir\u201D program managed by Agence Nationale pour la Recherche (grant number ANR-10-LABX-0013), and by the French regional council of Pays-de-le-Loire (VaCaRMe project). This work was also supported by the POPGEN project as part of the Plan France M\u00E9decine G\u00E9nomique 2025 (PFMG2025/ POPGEN) and by Inserm cross-cutting project GOLD. This work was also partially funded by a Swiss National Science Foundation project grant no. PP00P3_176977.; This work was supported by LABEX GENMED, funded as part of "Investissement d'avenir" program managed by Agence Nationale pour la Recherche (grant number ANR-10-LABX-0013), and by the French regional council of Pays-de-le-Loire (VaCaRMe project). This work was also supported by the POPGEN project as part of the Plan France Medecine Genomique 2025 (PFMG2025/POPGEN) and by Inserm cross-cutting project GOLD. This work was also partially funded by a Swiss National Science Foundation project grant no. PP00P3_176977.; FrEx Consortium, FranceGenRef Consortium, Herzig, A F, Rubinacci, S, Marenne, G & Génin, E 2025, 'SURFBAT : A surrogate family based association test building on large imputation reference panels', G3: Genes, Genomes, Genetics, vol. 15, no. 4, jkae287. https://doi.org/10.1093/g3journal/jkae287; https://hdl.handle.net/10138/596275; 105003784694; 001380016700001 |
| Availability: |
https://hdl.handle.net/10138/596275 |
| Rights: |
cc_by ; info:eu-repo/semantics/openAccess ; openAccess |
| Accession Number: |
edsbas.2EF1B795 |
| Database: |
BASE |