A genome‐wide search for quantitative trait loci affecting the cortical surface area and thickness of Heschl's gyrus

Abstract

Heschl's gyrus (HG) is a core region of the auditory cortex whose morphology is highly variable across individuals. This variability has been linked to sound perception ability in both speech and music domains. Previous studies show that variations in morphological features of HG, such as cortical surface area and thickness, are heritable. To identify genetic variants that affect HG morphology, we conducted a genome-wide association scan (GWAS) meta-analysis in 3054 healthy individuals using HG surface area and thickness as quantitative traits. None of the single nucleotide polymorphisms (SNPs) showed association P values that would survive correction for multiple testing over the genome. The most significant association was found between right HG area and SNP rs72932726 close to gene DCBLD2 (3q12.1; P = 2.77 × 10 −7 ). This SNP was also associated with other regions involved in speech processing. The SNP rs333332 within gene KALRN (3q21.2; P = 2.27 × 10 −6 ) and rs143000161 near gene COBLL1 (2q24.3; P = 2.40 × 10 −6 ) were associated with the area and thickness of left HG, respectively. Both genes are involved in the development of the nervous system. The SNP rs7062395 close to the X-linked deafness gene POU3F4 was associated with right HG thickness (Xq21.1; P = 2.38 × 10 −6 ). This is the first molecular genetic analysis of variability in HG morphology.

Lateralization of gene expression in human language cortex

“…This question may be approached using gene-set enrichment analysis and polygenic risk scores, in brain imaging genetics datasets produced for genome-wide association scanning (Cai et al, 2014;Guadalupe et al, 2015;Hibar et al, 2015;Thompson et al, 2014). Genetic association studies of individual candidate genes, that were not so far motivated by data on lateralized gene expression, have indicated that measures of languagerelated functional lateralization may associate with common genetic variants (Ocklenburg et al, 2013;Pinel et al, 2012).…”

A genome wide association study of fast beta EEG in families of European ancestry

“…Variation within DSE has been associated with several cancers (Gouignard et al, 2016a; Thelin et al, 2013, 2012), Heschl’s Gyrus thickness (Cai et al, 2014), and is also a notable risk factor for Ehlers-Danlos syndrome, with a subtype specifically linked to dysfunction of DSE (Müller et al, 2013). Recent work by Gouignard et al (Gouignard et al, 2016b) demonstrates a functional role for dse (the protein encoded by DSE ) in cranial neural crest cell migration and in cell adhesion providing a potential biological mechanism linking DSE dysfunction to Ehlers-Danlos syndrome and other neural crest related disorders (i.e., neurocristopathies); the knockdown of dse impaired the correct activation of transcription factors involved in the epithelial-mesenchymal transition and reduced the extent of neural crest cell migration, subsequently leading to a decrease in neural crest-derived craniofacial skeleton, melanocytes and dorsal fin structures.…”

Duffy antigen receptor genetic variant and the association with Interleukin 8 levels

“…This array only contains SNPs related to cardiovascular diseases and thus, the assumption of independence may not hold. We used instead an a priori defined threshold to define association in the discovery study, an approach used by other investigators analyzing quantitative traits [52]. Of importance, we were able to replicate our association in two independent populations where serum levels of IL8 were available.…”