Significant or suggestive linkage has been reported within regions on chromosomes 1p, 1q, 4q, 6p, 7p, 11p, 11q, 12q, 13q and 15q [23]–[26]. Shifman [27] reported a genome-wide association study for EPQ-N in 2,054 extreme-scoring individuals from a large cohort (patient registers of UK general practitioners) using eight DNA pools. No significant SNPs were identified under linkage peaks derived from sib pairs in the same cohort [14], [23]. They reported an association at SNP rs702543, in the phosphodiesterase 4D gene (PDE4D) on chromosome 5q, but even after individual genotyping of a further 1534 individuals from the same cohort, the combined p-value was not genome-wide significant (p = 2×10−6). Further analysis of rs702543 in a combined sample from three populations (Australian twins, Virginia Adult Twin registry, Netherlands twin families), using a measure of neuroticism that is similar to EPQ-N, showed a non-significant trend for an excess of the risk allele (A) in high neuroticism-score individuals. A family-based analysis revealed overtransmission of the A allele in high-score individuals from the Australian sample (p = 0.04), but not in the Netherlands sample. Thus,
