2025 Hyper Recent •CC0 1.0 Universal

This work is dedicated to the public domain. No rights reserved.

Access Preprint From Server
June 30th, 2025
Version: 1
Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, The Netherlands
evolutionary biology
biorxiv

Genetic variation in life-history traits is not correlated with estrogen-receptor positive breast cancer risk

Young, E. A.Open in Google Scholar•Erten, E. Y.Open in Google Scholar•Postma, E.Open in Google Scholar•Lummaa, V.Open in Google Scholar•van der Vegt, B.Open in Google Scholar•de Bock, G.Open in Google Scholar•Dugdale, H. L.Open in Google Scholar

Estrogen-receptor positive breast cancer (ER+ BC) is one of the most prevalent cancers, but the evolutionary processes shaping genetic variation in ER+ BC risk are poorly understood. Here, we explore evidence for antagonistic pleiotropy between ER+ BC risk and human life-history traits, testing whether increased genetic ER+ BC risk is indicative of life-history trade-offs, and is associated with faster maturation, earlier reproduction, and/or increased reproductive success. We estimate genome-wide genetic correlations between ER+ BC risk and three life-history traits (age at menarche, age at first birth, and the number of children born) for Lifelines biobank women using genomic restricted maximum likelihood analyses. We complement these by - for the first time - performing linkage disequilibrium score regression on European family-based genome-wide association study data. Regardless of the data or method used, genetic correlations were low and not statistically different from zero. Thus, we find no evidence for antagonistic pleiotropy between ER+ BC risk and life-history traits, suggesting that these germline mutations have instead accumulated due to weak selection at older ages. Our quantitative genetic analyses suggest that previous results showing antagonistic pleiotropy for individual genetic variants do not replicate when accounting for these traits\' polygenic nature and that observed phenotypic trends do not have a genetic underpinning. While we find no evidence for life-history trade-offs shaping genetic risk for ER+ BC, our rigorous approach may provide a template for future studies to test the role of life-history trade-offs in shaping genetic risk for other diseases.

Similar Papers

biorxiv
Mon Jun 30 2025
Reduced regulatory complexity associated with the evolutionary transition to sociality from cockroaches to termites despite evolutionary parallels with Hymenoptera
The degree of phenotypic diversity within social species has previously been associated with more complex genetic regulation both in cis and trans contexts. Transcription factors (TFs) being key to genetic regulation, have been studied in the origins of eusociality in Hymenoptera (bees, ants and wasps) but less so in Blattodea (cockroaches and termites). Here we show that the social transition in ...
Jones, A.
•
Dohmen, E.
•
Berger, J.
•
Legendre, F.
...•
Bornberg-Bauer, E.
biorxiv
Mon Jun 30 2025
Lifestyles shape genome size and gene content in fungal pathogens
Fungi display a wide range of lifestyles and hosts. We still know little about the impact of lifestyles, including pathogenicity, on their genome architecture. Here, we combined and annotated 552 fungal genomes from the class Sordariomycetes and examined the association between 13 genomic and two lifestyle traits: pathogenicity and insect association. We found that pathogens on average tend to hav...
Fijarczyk, A.
•
Hessenauer, P.
•
Hamelin, R. C.
•
Landry, C. R.
biorxiv
Mon Jun 30 2025
Temperature and pH universally govern protein diversity in hydrothermal spring communities, but they do so differently
It has been suggested that temperature and pH are strong explanatory causes of protein evolutionary constraint. However, a general understanding of how changes in temperature and pH may universally impact protein evolution is lacking. Moreover, while pH is locally regulated in the different microbial compartments (e.g. periplasm, cytoplasm), temperature is not. A priori, these variables should act...
Rivas-Santisteban, J.
•
Alcorta, J.
•
Diez, B.
•
Tamames, J.
•
Pedros-Alio, C.
biorxiv
Mon Jun 30 2025
Chromatin accessibility differences between the hybrids of nasuta-albomicans complex of Drosophila
Understanding how chromosomal rearrangements (CRs) interact with epigenetic changes to drive speciation is a fundamental question in evolutionary biology. CRs are key contributors to chromosome evolution and can play a pivotal role in reproductive isolation. The Drosophila nasuta-albomicans species complex presents an ideal model to explore this, as D. albomicans possesses neo-sex chromosomes form...
Padma, R.
•
Patil, A. B.
•
Vijay, N.
biorxiv
Mon Jun 30 2025
Phylogenomics supports island contribution to metapopulation dynamics in a predominantly continental bird species
Aim: Islands have recently been recognized as potential sources of biodiversity, challenging the traditional view that their small population sizes and low genetic diversity limit such roles. This raises the question of how insular genetic variation becomes incorporated into continental populations, contrary to expectations of unidirectional colonization. Here, we investigate whether and how islan...
Aoki, D.
•
Senzaki, M.
•
Ando, H.
•
Odaya, Y.
...•
Kondo, N.
biorxiv
Mon Jun 30 2025
Improved Genotype Inference Reveals Cis- and Trans-Driven Variation in the Loss-of-Heterozygosity Rates in Yeast
Loss-of-heterozygosity (LOH) events are an important source of genetic variation in diploids and are implicated in cancer. LOH-event rates vary across the genome and across genetic backgrounds, but our understanding of this variation is in its infancy. State-of-the-art measurements of LOH rates are obtained from mutation accumulation (MA) experiments in heterozygous hybrids and hinge on the accura...
Overton, M. S.
•
Kryazhimskiy, S.
biorxiv
Sun Jun 29 2025
Barriers Broken: Genetic Swamping in Restored Brook Trout Populations
Scientists use reintroductions to restore native species to their historical ranges but sometimes can overlook the effects of dispersal on the genetic structure of restored populations. In the Great Smoky Mountains National Park (GRSM), an ambitious reintroduction strategy aims to restore native Brook Trout (Salvelinus fontinalis) populations, which have lost over 75% of their historical habitat w...
Smith, R.
•
Fitzpatrick, B.
•
Kulp, M.
biorxiv
Sat Jun 28 2025
A century of allopatry: plasticity and rapid selection shape phenotypic trait variability under contrasting environments.
Allopatric isolation under contrasting environments can drive rapid phenotypic divergence, even over contemporary timescales. Rapid changes in morphology or physiology can allow organisms to adapt to biotic and abiotic characteristics of their habitats. However, multiple types of traits, such as physiological and morphological traits, are rarely jointly considered, although this could reveal adapt...
Rogissart, H.
•
Daufresne, M.
•
Evanno, G.
•
Guillard, J.
...•
Raffard, A.
biorxiv
Sat Jun 28 2025
Diet as a driver of natural selection in human evolution: a paleo-empirical perspective
Ancient DNA-based selection scans have revealed multiple diet-associated single nucleotide polymorphisms (SNPs) that exhibit robust signatures of natural selection. To test whether the selection was indeed driven by diet, we conducted a paleo-empirical investigation. We compiled an isotopic dataset comprising 6,064 ancient human samples and 5,635 food resource samples from Britain. We developed a ...
CHEN, Z.