Cosmopolitan inversions have a major impact on trait variation and the power of different GWAS approaches to identify associations
Benedict Adam Lenhart, Alan O. Bergland
Abstract
The ability of genomic inversions to reduce recombination and generate linkage can have a major impact on genetically based phenotypic variation in populations. However, the increase in linkage associated with inversions can create hurdles for identifying associations between loci linked to inversions and the traits they impact.
Introduction
Genomic inversions facilitate adaptation by suppressing recombination and generating linkage between many genes and mutations, therefore affecting the genetic basis and evolution of complex traits [1–5]. The adaptive importance of inversions for the evolution of novelty, local adaptation, and speciation is clear from a wide variety of organisms across the tree of life (reviewed in [6–10]). Despite the prevalent role of inversions in evolution, the role of inversions underlying phenotypic variation is often overlooked within association studies [11].
Materials and methods
Selection of trait data
We re-analyzed trait data collected on the DGRP [46]. We made use of the DGRPool resource, which has consolidated the phenotypic line averages of inbred DGRP lines from many publications [49]. We used the “curated” data, and removed traits from this dataset that describe genomic features such as genome size or transposon presence, or used less than 75 unique DGRP lines, ending up with 409 unique traits derived from 36 publications (S1 Table).
Results
Cosmopolitan inversions impact phenotypic variation
To study the role of inversions on genetically based trait variation in D. melanogaster, we re-analyzed data from publications that measured trait variation in the DGRP and were curated in the DGRPool database [49]. We analyzed 409 traits, categorizing them into five groups: morphological, life-history, stress resistance, physiological, and behavioral (S1 Table). We found that In(2L)t, In(3R)Mo, and In(3R)K are associated with more traits than expected given SNPs of the same frequency (Fig 1A).
Discussion
Genomic inversions can simultaneously influence multiple traits and provide a mechanism for adaptation. Associations between inversions and phenotypic variation have been identified across the tree of life, along with evidence that natural selection acts upon these genomic features [6,7,8]. Here, we find that inversions within D. melanogaster impact a suite of diverse traits (Figs 1A, 2C, and 2D), and specific statistical methods are better equipped to map associations between inversion-linked loci and these traits.
Acknowledgments
We thank Research Computing at UVA for the use of computational resources, and for the staff’s patient and consistent support (https://rc.virginia.edu), and John Teurman for his work annotating information from Drosophila publications.
Citation: Lenhart BA, Bergland AO (2026) Cosmopolitan inversions have a major impact on trait variation and the power of different GWAS approaches to identify associations. PLoS Genet 22(1): e1012012. https://doi.org/10.1371/journal.pgen.1012012
Editor: Russell Corbett-Detig, UC Santa Cruz, UNITED STATES OF AMERICA
Received: April 28, 2025; Accepted: December 22, 2025; Published: January 5, 2026
Copyright: © 2026 Lenhart, Bergland. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: The DGRP’s Wolbachia infection status and inversions genotype table are all available from the DGRP website (https://quantgenet.msu.edu/dgrp/downloads.html). The aggregated DGRP phenotype data is available from the DGRPool website (https://dgrpool.epfl.ch/). Doi access to individual publications is available within S1 Table. All other data and analysis scripts, including the relevant DGRP genome data, are archived on Zenodo and publicly available at https://zenodo.org/records/17946913. The associated GitHub repository is available at https://github.com/benedictlenhart/InversionGWAS.
Funding: We are supported by the NSF BIO-DEB (EP) award # 2145688, NIH NIGMS award # R35GM119686 to AOB, start-up funds provided by UVA to AOB, and by a fellowship from the Jefferson Foundation to BAL. BAL received salary support from the Jefferson Scholars Foundation and AOB received salary support from UVA, NSF, and NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
