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What makes us human: genomic insights into cognition, language, migration, and mental health
Dissertation   Open access

What makes us human: genomic insights into cognition, language, migration, and mental health

Lucas Casten
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Autumn 2025
DOI: 10.25820/etd.008218
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Abstract

This thesis investigates how ancient genetic changes shaped the traits that define our species and continue to influence how we think and act. Through four studies integrating evolutionary genomics, behavioral genetics, and psychiatric research across nearly 500,000 participants, this work demonstrates that human distinctiveness arose primarily through regulatory rewiring rather than novel proteins, with subtle changes in gene expression timing and location during brain development. These changes created the foundations for language, exploration, and self-reflection. Chapter 2 reveals that Human Ancestor Quickly Evolved Regions (HAQERs), comprising less than 0.1% of the genome, have a disproportionate effect on individual differences in human language abilities, show balancing selection across 20,000 years, and convergent evolution across vocal learning mammals. Chapter 3 establishes that migration propensity is moderately heritable (SNP h2 ∼5%), with migration-associated variants enriched around genes highly expressed in cortical excitatory neurons, and migration polygenic scores predict both ancient population movements across 10,000 years and modern regional economic growth, revealing how cognitive and motivational systems underpin human adaptability. Chapter 4 uncovers a paradox where exceptional cognitive ability is associated with a ∼6-fold higher risk for suicidal thoughts in children with autism, with polygenic scores for cognition predicting suicidal thoughts in neurodiverse populations. Chapter 5 introduces Lingo, an online phenotyping platform achieving up to 10-fold greater statistical power for genetic associations than traditional measures, enabling population-scale studies while revealing distinct genetic architectures across language components. Collectively, this work reveals that the genetic changes underlying human evolution are not relics of the past but actively contribute to present-day diversity, shaping individual differences in cognition, behavior, and mental health.
Bioinformatics Evolution Psychiatry Behavioral genetics Cognition Human genetics Language

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