Identifying candidate genes underlying isolated congenital anosmia.

An estimated 1 in 10 000 people are born without the ability to smell, a condition known as congenital anosmia, and about one third of those people have non-syndromic, or isolated congenital anosmia (ICA). Despite the significant impact of olfaction for our quality of life, the underlying causes of ICA remain largely unknown. Using whole exome sequencing (WES) in 10 families and 141 individuals with ICA, we identified a candidate list of 162 rare, segregating, deleterious variants in 158 genes. We confirmed the involvement of CNGA2, a previously implicated ICA gene that is an essential component of the olfactory transduction pathway. Furthermore, we found a loss-of-function variant in SREK1IP1 from the family gene candidate list, which was also observed in 5% of individuals in an additional non-family cohort with ICA. Although SREK1IP1 has not been previously associated with olfaction, its role in zinc ion binding suggests a potential influence on olfactory signaling. This study provides a more comprehensive understanding of the spectrum of genetic alterations and their etiology in ICA patients, which may improve the diagnosis, prognosis, and treatment of this disorder and lead to better understanding of the mechanisms governing basic olfactory function.

Odor valence linearly modulates attractiveness, but not age assessment, of invariant facial features in a memory-based rating task.

Scented cosmetic products are used across cultures as a way to favorably influence one's appearance. While crossmodal effects of odor valence on perceived attractiveness of facial features have been demonstrated experimentally, it is unknown whether they represent a phenomenon specific to affective processing. In this experiment, we presented odors in the context of a face battery with systematic feature manipulations during a speeded response task. Modulatory effects of linear increases of odor valence were investigated by juxtaposing subsequent memory-based ratings tasks--one predominantly affective (attractiveness) and a second, cognitive (age). The linear modulation pattern observed for attractiveness was consistent with additive effects of face and odor appraisal. Effects of odor valence on age perception were not linearly modulated and may be the result of cognitive interference. Affective and cognitive processing of faces thus appear to differ in their susceptibility to modulation by odors, likely as a result of privileged access of olfactory stimuli to affective brain networks. These results are critically discussed with respect to potential biases introduced by the preceding speeded response task.