Variant selection to maximize variance explained in cis-Mendelian randomization

Human Genetics and Genomics Advances 2026 Open access

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Authors: Ang Zhou, Ville Karhunen, Haodong Tian, Janne Pott, Ashish Patel, Eric A. W. Slob, Stephen Burgess
DOI: 10.1016/j.xhgg.2026.100573
Cited by: 2
References: 19

Abstract

of 145.1% compared with the lead variant alone (range: 69.6%-169.4%), with a median reduction in the MR standard error of 36.3% (range: -37.9% to -19.3%). In simulations, all methods were able to recover the expected genetic variance. Across the 15 gene regions, methods incorporating non-lead variants consistently outperformed the lead-variant-only approach. Variant selection methods incorporating correlated non-lead variants can reliably improve instrument strength in cis-MR analyses. We recommend using such methods but advise comparing their estimates with the lead-variant-only estimate to safeguard against numerical instability.

Fields of Study & Subjects

Genetic Associations and Epidemiology Genomics and Rare Diseases Bioinformatics and Genomic Networks

Publication details

Journal / source
Human Genetics and Genomics Advances
Publisher
Elsevier BV
Volume
7
Issue
2
Pages
100573–100573
Publication date
18 January 2026
Language
EN