The present findings represent a demonstration of an association between common gene variation and neural function associated with face processing. Validation of some of the initial results using a parallel experiment and replication of the most promising candidates in an independent population was used. It is also important to note that the original associations with fusiform gyrus activation in the Norwegian discovery sample were identified when searching across all neural regions sensitive to the task and not through the narrow window of an anatomical region of interest approach.
There is little knowledge about the function of the genes that were identified, but there are some indications that TMEM212
is expressed in the brain. Affymetrix provides a test of whether a transcript is present or absent within a sample,29
is present in five out of seven samples of the whole brain tissue collated in the Gene Enrichment Profiler30
), and in one out of two samples from the occipital lobe.
Interestingly, both genes replicated in the North American sample lie within regions for which associations have been proposed to disorders involving impairment of social functioning.31, 32, 33, 34, 35
But, as no association to diagnosis was found, and the replication sample excludes any individuals with a current DSM-IV (Diagnostic and Statistical Manual for Mental Disorders) Axis I disorder, we believe these genes to be involved in regulating fundamental brain functions related to face processing unrelated to psychiatric disorders. Further, as these variants were identified and validated using faces expressing negative and positive emotions, these pathways may be broadly important for face processing independent of emotional expression.
The current findings are in line with recent evidence of high heritability of the ability to process face information,12, 13
which suggests a strong biological control of this important human function. Previous studies indicate that the ability for face recognition has little overlap with other cognitive abilities,12, 13
which suggests that the face processing ability is specific. This is supported by the present findings of specific activation patterns related to face processing associated with distinct gene variants, indicating a specific genetic basis. Particularly TMEM212
seems to be specifically involved in the innate architecture of face processing, as it was associated with activation in the FFA only.
This supports the position that distinct cognitive and neuronal mental processes may have specific genetic determinants, as has been seen with language disability.36
Thus, the genes identified in the current study would be interesting candidate genes to investigate for association with developmental prosopagnosia,37
a disorder characterized by impairments in face recognition that are unaccompanied by brain lesions; multiple cases of this disorder have been seen in the same family.38, 39
Investigations into pedigrees has suggested that forms of congenital prosopagnosia can have a dominant, autosomal mode of inheritance.40
Although we have looked for common variation, these genes could be investigated to find rare variants causing pathological results in such families. However, the development of such distinct mental processes probably depends on gene–environment interactions.
To conclude, specific genes that may be important for the modulation of basic neurobiological processes, which underlie human social interactions, have been identified. In addition, we have demonstrated how the synthesis of fMRI and genome-wide data can be used to discover and replicate links between common genomic variation and behaviorally relevant brain function.