The Imprinted Gene LRRTM1 Mediates Schizotypy and Handedness in a Nonclinical Population
Overview
Affiliations
Imprinted genes have been posited to have important roles in human brain development and cognition, but their effects in nonclinical populations have yet to be investigated. Single-nucleotide polymorphisms (SNPs) of the imprinted gene LRRTM1 have previously been associated with schizophrenia risk and with handedness in individuals with dyslexia. We tested the hypothesis that genetic variation (SNPs) and epigenetic variation (methylation) in this gene are associated with schizotypy and handedness in a nonclinical population. Risk alleles of the three schizophrenia-linked SNPs were associated with significantly and substantially higher levels of total schizotypy. Variation in SNP genotypes was not associated with handedness, but levels of methylation in a block of CpG sites in the putative LRRTM1 promoter region were associated with more-mixed handedness. These findings provide evidence of continuity between schizophrenia and schizotypy with regard to the psychological effects of allelic variation in this imprinted gene, and show that epigenetic variation in an imprinted gene mediates the development and expression of human handedness.
Epigenome Defines Aberrant Brain Laterality in Major Mental Illnesses.
Mostafavi Abdolmaleky H, Nohesara S, Thiagalingam S Brain Sci. 2024; 14(3).
PMID: 38539649 PMC: 10968810. DOI: 10.3390/brainsci14030261.
Perez de Arce K, Ribic A, Chowdhury D, Watters K, Thompson G, Sanganahalli B Nat Commun. 2023; 14(1):459.
PMID: 36709330 PMC: 9884278. DOI: 10.1038/s41467-023-36042-w.
Distinct but overlapping roles of LRRTM1 and LRRTM2 in developing and mature hippocampal circuits.
Dhume S, Connor S, Mills F, Karimi Tari P, Au-Yeung S, Karimi B Elife. 2022; 11.
PMID: 35662394 PMC: 9170246. DOI: 10.7554/eLife.64742.
DNA methylation in peripheral tissues and left-handedness.
Odintsova V, Suderman M, Hagenbeek F, Caramaschi D, Hottenga J, Pool R Sci Rep. 2022; 12(1):5606.
PMID: 35379837 PMC: 8980054. DOI: 10.1038/s41598-022-08998-0.
Polygenic scores for handedness and their association with asymmetries in brain structure.
Ocklenburg S, Metzen D, Schluter C, Fraenz C, Arning L, Streit F Brain Struct Funct. 2021; 227(2):515-527.
PMID: 34235564 PMC: 8844179. DOI: 10.1007/s00429-021-02335-3.