We present a comprehensive analysis of a population-based sample for genome-wide association with neuroticism. The evidence from 19 cryptic first-degree relative pairs in our study suggests a heritability for EPQ-N of at most 0.22, lower than the previously-reported range of 0.3 to 0.5. We identified SNPs in NKAIN2 showing evidence for an additive main effect, but short of genome-wide significance. This gene has been linked with neurological phenotypes [41], though little functional or molecular information is available. Several SNPs in gene GPC6 on 13q gave a signal for an interaction with age. GPC6 is known to be involved in the regulation of the Wnt pathway [42] that plays a role in intracellular signalling both during neural development [43] and also in the mature nervous system with possible implication in synaptic modulation and plasticity. There is some evidence that abnormalities of signal transduction may be implicated in the pathophysiology of psychiatric disorders, including mood disorders and schizophrenia [44], [45]. Several studies also suggest that Wnt-pathway abnormalities may play a role in neurodegenerative process and Alzheimer disease [46], [47]. Neuroticism, alone or in combination with other personality traits or lifestyle, has been shown to be predictive for Alzheimer [5], [48].
