Analysis of genetics and brain imaging of handedness

Takeaway

  • Handedness is associated with four significant loci that contribute to brain development and language networks, and left handedness is correlated positively with schizophrenia and negatively with Parkinson’s disease (PD).

Why this matters

  • Even though 90% of the population is right-handed, the unique physical characteristics of the brain and genetics that cause handedness are unknown due to small sample sizes in previous studies.

  • Left handedness is associated with schizophrenia and negatively correlated with PD; therefore, understanding characteristics of handedness may lead to improved clinical diagnosis and treatment.

Study design

  • Objective: to determine relationships between handedness, genotypes, and image-derived phenotypes (IDP).

  • Left-handed people (n=721) and right-handed people (n=6,685) participated in a magnetic resonance imaging scan to identify important IDP.

  • A genome-wide association study (GWAS) was conducted with left-handed (n=38,332), right-handed (n=356,567), and ambidextrous (n=6,299) people.

  • Single nucleotide polymorphism (SNP)-based enrichment analysis, gene-based analysis, and tissue type analysis were performed on this data to identify important biological pathways.

Key results

  • Left-handed people had stronger connectivity between the right- and left-brain language networks.

  • Four significant loci (rs199512, rs45608532, rs3094128, and rs13017199) were found to be different between left- and right-handed people.

    • Locus rs13017199 is associated with microtubule-associated protein 2.

    • Locus rs3094128 is associated with tubulin beta class 1.

    • Locus rs199512 is associated with microtubule-associated protein tau.

  • The loci identified from the GWAS were associated with neuronal morphogenesis, differentiation, migration, and gliogenesis.

  • Left handedness was correlated with schizophrenia (r=0.1324; P=0.0021), PD (r=-0.2379; P=0.0071), anorexia nervosa (r=0.1504; P=0.1504), and bipolar disorder (r=0.1548; P=0.025).

  • Left handedness was negatively associated with PD (P=0.004) and positively associated with language networks.

Limitations

  • None reported.