School of Medicine Publications and Presentations

Document Type

Article

Publication Date

12-2024

Abstract

National and international biobanking efforts led to the collection of large and inclusive imaging genetics datasets that enable examination of the contribution of genetic and environmental factors to human brains in illness and health. High-resolution neuroimaging (~104–6 voxels) and genetic (106–8 single nucleotide polymorphic [SNP] variants) data are available in statistically powerful (N = 103–5) epidemiological and disorder-focused samples. Performing imaging genetics analyses at full resolution afforded in these datasets is a formidable computational task even under the assumption of unrelatedness among the subjects. The computational complexity rises as ~N2–3 (where N is the sample size), when accounting for relatedness among subjects. We describe fast, non-iterative simplifications to accelerate classical variance component (VC) methods including heritability, genetic correlation, and genome-wide association in dense and complex empirical pedigrees. These approaches linearize (from N2–3 to N~1) computational effort while maintaining fidelity (r ~ 0.95) with the VC results and take advantage of parallel computing provided by central and graphics processing units (CPU and GPU). We show that the new approaches lead to a 104- to 106-fold reduction in computational complexity—making voxel-wise heritability, genetic correlation, and genome-wide association studies (GWAS) analysis practical for large and complex samples such as those provided by the Amish and Human Connectome Projects (N = 406 and 1052 subjects, respectively) and UK Biobank (N = 31,681). These developments are shared in open-source, SOLAR-Eclipse software.

Comments

© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Creative Commons License

Creative Commons Attribution-NonCommercial 4.0 International License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License

Publication Title

Human Brain Mapping

DOI

https://doi.org/10.1002/hbm.70044

Academic Level

faculty

Mentor/PI Department

Office of Human Genetics

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