Robust inference and widespread genetic correlates from a large-scale genetic association study of human personality

Schwaba, T.; Clapp Sullivan, M. L.; Akingbuwa, W. A.; Ilves, K.; Tanksley, P. T.; Williams, C. M.; Dragostinov, Y.; Liao, W.; Ackerman, L. S.; Fealy, J. C. M.; Hemani, G.; de la Fuente, J.; Gupta, P.; Stein, M. B.; Gelernter, J.; Levey, D. F.; Vosa, U.; Ausmees, L.; Realo, A.; Estonian Biobank Research Team,; Vaht, M.; Allik, J.; Esko, T.; Mottus, R.; Vainik, U.; Jonsdottir, G. A.; Thorleifsson, G.; Gunnarsson, A. F.; Bjornsdottir, G.; Thorgeirsson, T. E.; Steffansson, H.; Stefansson, K.; Cheesman, R.; Qin, Q.; Corfield, E. C.; Ask, H.; Ask Torvik, F.; Ystrom, E.; Tesli, M.; Boomsma, D. I.

doi:10.1101/2025.05.16.648988

Home/Archive/bioRxiv

bioRxiv · 10.1101/2025.05.16.648988

Robust inference and widespread genetic correlates from a large-scale genetic association study of human personality

View original source ↗Export metadata ↓

Abstract

Personality traits describe stable differences in how individuals think, feel, and behave and how they interact with and experience their social and physical environments. We assemble data from 46 cohorts including 611K-1.14M participants with European-like and African-like genomes for genome-wide association studies (GWAS) of the Big Five personality traits (extraversion, agreeableness, conscientiousness, neuroticism, and openness to experience), and data from 51K participants for within-family GWAS. We identify 1,257 lead genetic variants associated with personality, including 823 novel variants. Common genetic variants explain 4.8%-9.3% of the variance in each trait, and 10.5%-16.2% accounting for measurement unreliability. Genetic effects on personality are highly consistent across geography, reporter (self vs. close other), age group, and measurement instrument, and we find minimal spousal assortment for personality in recent history. In stark contrast to many other social and behavioral traits, within-family GWAS and polygenic index analyses indicate little to no shared environmental confounding in genetic associations with personality. Polygenic prediction, genetic correlation, and Mendelian randomization analyses indicate that personality genetics have widespread, potentially causal associations with a wide range of consequential behaviors and life outcomes. The genetic architecture of personality is robust and fundamental to being a human.

Explore related subjects

genomics Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Schwaba, T., Clapp Sullivan, M. L., Akingbuwa, W. A., Ilves, K., Tanksley, P. T., Williams, C. M., Dragostinov, Y., Liao, W., Ackerman, L. S., Fealy, J. C. M., Hemani, G., de la Fuente, J., Gupta, P., Stein, M. B., Gelernter, J., Levey, D. F., Vosa, U., Ausmees, L., Realo, A., Estonian Biobank Research Team,, Vaht, M., Allik, J., Esko, T., Mottus, R., Vainik, U., Jonsdottir, G. A., Thorleifsson, G., Gunnarsson, A. F., Bjornsdottir, G., Thorgeirsson, T. E., Steffansson, H., Stefansson, K., Cheesman, R., Qin, Q., Corfield, E. C., Ask, H., Ask Torvik, F., Ystrom, E., Tesli, M., Boomsma, D. I.. 2025-05-20. Robust inference and widespread genetic correlates from a large-scale genetic association study of human personality. https://doi.org/10.1101/2025.05.16.648988

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Integrative Nanopore and Illumina sequencing reveals age-associated tRNA modification and CCA-tail dynamics in yeast

Aging is characterized by a progressive loss of proteostasis. Transfer RNAs (tRNAs) are essential regulators of translation, yet their dynamics during aging remain poorly understood due to challenges in sequencing highly modified RNAs. Here we present a benchmarked Nanopore direct RNA sequencing (RNA004 chemistry) resource that profiles the Saccharomyces cerevisiae tRNAome during replicative aging at single-molecule resolution. Using in vitro transcribed tRNA controls, we establish modification detection thresholds and validate key findings with orthogonal Illumina sequencing. While overall tRNA abundance remains largely stable, our resource reveals age-associated terminal A cleavage at the 3' CCA tail of mature tRNAs, targeted T-loop and anticodon modification changes, and single-molecule evidence of modification co-occurrence. This dataset provides a resource for exploring tRNA regulation, translation fidelity, and longevity.

genomics↗

bioRxiv2026

A hydrogen-producing mitochondrion in an anaerobic eukaryotrophic rhizarian

Diverse eukaryotes thrive under low oxygen conditions, in part through highly modified mitochondrion-related organelles (MROs) that use alternate metabolic pathways to support ATP production and cofactor recycling. Anaerobic lifestyles have evolved repeatedly across the eukaryotic tree of life, each providing an independent opportunity to understand how eukaryotes adapt to life in low oxygen conditions. Here, we use single-cell transcriptomics to reconstruct the MRO metabolism of PCE SSF, a benthic eukaryotrophic flagellate and the first cultivated representative of Novel Clade 12 (NC12; Rhizaria), an independently anaerobic rhizarian lineage. PCE SSF possesses an anaerobic hydrogen-producing mitochondrion capable of hydrogenosome-type substrate-level phosphorylation. It also retains a nearly complete but likely branched tricarboxylic acid pathway that lacks citrate synthase and malate dehydrogenase. The function of citrate synthase may instead be fulfilled by the typically cytosolic ATP citrate lyase, previously reported in this context only in the anaerobic cercozoan, Brevimastigomonas motovehiculus. Unlike B. motovehiculus, however, PCE SSF retains only Complex II and the NuoE/NuoF subunits of the electron transport chain and lacks a mitochondrial genome. Together, these features indicate an atypical and reduced mitochondrial metabolism, highlighting the diversity of evolutionary solutions to anaerobic energy metabolism in eukaryotes.

genomics↗

bioRxiv2026

Targeted CRISPRi screening reveals unexpected resilience across the RNA polymerase III transcriptome

Increased RNA polymerase III (Pol III) activity and tRNA abundance are widely linked to cancer cell growth, yet the functional requirement for individual Pol III genes and core components remains unclear, in part due to the difficulty of achieving gene-specific perturbation of highly conserved loci. Here, we developed an inducible CRISPR interference platform and a custom single-guide RNA (sgRNA) library enabling gene-specific targeting of Pol III-transcribed genes and Pol III machinery. Genome-wide screening identified several Pol III dependencies in diploid fibroblasts and HEK293T cells, including multiple initiator methionine tRNA genes among the strongest fitness dependencies. Unexpectedly, glioblastoma models remained largely insensitive to repression of both individual Pol III genes and core Pol III components, despite efficient target repression. These findings establish a general strategy for gene-specific interrogation of conserved Pol III genes and indicate that glioblastoma models tolerate extensive perturbation of Pol III genes and machinery.

genomics↗