Data Integration Methods for Phenotype Harmonization in Multi-Cohort Genome-Wide Association Studies With Behavioral Outcomes

Parallel meta-analysis is a popular approach for increasing the power to detect genetic effects in genome-wide association studies across multiple cohorts. Consortia studying the genetics of behavioral phenotypes are oftentimes faced with systematic differences in phenotype measurement across cohorts, introducing heterogeneity into the meta-analysis and reducing statistical power. This study investigated integrative data analysis (IDA) as an approach for jointly modeling the phenotype across multiple datasets. We put forth a bi-factor integration model (BFIM) that provides a single common phen... Mehr ...

Verfasser: Luningham, Justin M
McArtor, Daniel B
Hendriks, Anne M
van Beijsterveldt, Catharina E M
Lichtenstein, Paul
Lundström, Sebastian
Larsson, Henrik
Bartels, Meike
Boomsma, Dorret I
Lubke, Gitta H
Dokumenttyp: Artikel
Erscheinungsdatum: 2019
Reihe/Periodikum: Luningham , J M , McArtor , D B , Hendriks , A M , van Beijsterveldt , C E M , Lichtenstein , P , Lundström , S , Larsson , H , Bartels , M , Boomsma , D I & Lubke , G H 2019 , ' Data Integration Methods for Phenotype Harmonization in Multi-Cohort Genome-Wide Association Studies With Behavioral Outcomes ' , Frontiers in Genetics , vol. 10 , 1227 , pp. 1-16 . https://doi.org/10.3389/fgene.2019.01227
Schlagwörter: consortia / data integration / genome-wide association studies / latent variable modeling / phenotype harmonization / /dk/atira/pure/keywords/cohort_studies/netherlands_twin_register_ntr_ / name=Netherlands Twin Register (NTR)
Sprache: Englisch
Permalink: https://search.fid-benelux.de/Record/base-29210681
Datenquelle: BASE; Originalkatalog
Powered By: BASE
Link(s) : https://research.vu.nl/en/publications/062df680-8b54-42bf-b768-44b90011987a

Parallel meta-analysis is a popular approach for increasing the power to detect genetic effects in genome-wide association studies across multiple cohorts. Consortia studying the genetics of behavioral phenotypes are oftentimes faced with systematic differences in phenotype measurement across cohorts, introducing heterogeneity into the meta-analysis and reducing statistical power. This study investigated integrative data analysis (IDA) as an approach for jointly modeling the phenotype across multiple datasets. We put forth a bi-factor integration model (BFIM) that provides a single common phenotype score and accounts for sources of study-specific variability in the phenotype. In order to capitalize on this modeling strategy, a phenotype reference panel was utilized as a supplemental sample with complete data on all behavioral measures. A simulation study showed that a mega-analysis of genetic variant effects in a BFIM were more powerful than meta-analysis of genetic effects on a cohort-specific sum score of items. Saving the factor scores from the BFIM and using those as the outcome in meta-analysis was also more powerful than the sum score in most simulation conditions, but a small degree of bias was introduced by this approach. The reference panel was necessary to realize these power gains. An empirical demonstration used the BFIM to harmonize aggression scores in 9-year old children across the Netherlands Twin Register and the Child and Adolescent Twin Study in Sweden, providing a template for application of the BFIM to a range of different phenotypes. A supplemental data collection in the Netherlands Twin Register served as a reference panel for phenotype modeling across both cohorts. Our results indicate that model-based harmonization for the study of complex traits is a useful step within genetic consortia.