Authors
Danfeng Chen, Katherine Tashman, Duncan S Palmer, Benjamin Neale, Kathryn Roeder, Alex Bloemendal, Claire Churchhouse, Zheng Tracy Ke
Publication date
2022/2/1
Journal
Human Molecular Genetics
Volume
31
Issue
3
Pages
481-489
Publisher
Oxford University Press
Description
The use of external controls in genome-wide association study (GWAS) can significantly increase the size and diversity of the control sample, enabling high-resolution ancestry matching and enhancing the power to detect association signals. However, the aggregation of controls from multiple sources is challenging due to batch effects, difficulty in identifying genotyping errors and the use of different genotyping platforms. These obstacles have impeded the use of external controls in GWAS and can lead to spurious results if not carefully addressed. We propose a unified data harmonization pipeline that includes an iterative approach to quality control and imputation, implemented before and after merging cohorts and arrays. We apply this harmonization pipeline to aggregate 27 517 European control samples from 16 collections within dbGaP. We leverage these harmonized controls to conduct a GWAS of …
Total citations
2023202442
Scholar articles
D Chen, K Tashman, DS Palmer, B Neale, K Roeder… - Human Molecular Genetics, 2022