The Molecular Genetic Architecture of Self-Employment

Economic variables such as income, education, and occupation are known to affect mortality and morbidity, such as cardiovascular disease, and have also been shown to be partly heritable. However, very little is known about which genes influence economic variables, although these genes may have both a direct and an indirect effect on health. We report results from the first large-scale collaboration that studies the molecular genetic architecture of an economic variable-entrepreneurship-that was operationalized using self-employment, a widely-available proxy. Our results suggest that common SNPs when considered jointly explain about half of the narrow-sense heritability of self-employment estimated in twin data (σg2/σP2= 25%, h2= 55%). However, a meta-analysis of genome-wide association studies across sixteen studies comprising 50,627 participants did not identify genome-wide significant SNPs. 58 SNPs with p<10-5were tested in a replication sample (n = 3,271), but none replicated. Furthermore, a gene-based test shows that none of the genes that were previously suggested in the literature to influence entrepreneurship reveal significant associations. Finally, SNP-based genetic scores that use results from the meta-analysis capture less than 0.2% of the variance in self-employment in an independent sample (p≥0.039). Our results are consistent with a highly polygenic molecular genetic architecture of self-employment, with many genetic variants of small effect. Although self-employment is a multi-faceted, heavily environmentally influenced, and biologically distal trait, our results are similar to those for other genetically complex and biologically more proximate outcomes, such as height, intelligence, personality, and several diseases

The adverse impact of surveillance intervals on the sensitivity of FDG-PET/CT for the detection of distant metastases in head and neck cancer patients

The presence of distant metastases at initial evaluation influences treatment selection, since no effective systemic treatment for disseminated head and neck squamous cell carcinoma (HNSCC) is currently available. The reported sensitivity for the detection of distant metastases by contrast-enhanced (ce)CT and FDG-PET(/CT) differs substantially between studies. We hypothesized that these sensitivity values are highly dependent on the reference standard use, e.g., follow-up term. Therefore, we analyze our results of FDG-PET/CT (including chest ceCT) with long-term follow-up and compare these findings with data from the literature, with particular interest in the different reference standards. Forty-six HNSCC patients with high-risk factors underwent pretreatment screening for distant metastases by FDG-PET/CT (including chest ceCT). In 16 (35%) patients, distant metastases were detected during screening (6 patients) or during a mean follow-up of 39.4 months after screening (10 patients). The sensitivity and negative predictive value were 83.3 and 97.2% when 6 months, 60.0 and 89.9% when 12 months, and 37.5 and 72.2% when 30 months follow-up were used as reference standard, respectively. This is comparable with reported studies with similar reference standards. This critical appraisal on the reference standards used in our and reported studies shows room for improvement for the detection of distant metastases to refrain more patients from unnecessary extensive locoregional treatment for occult metastatic HNSCC

Screening for distant metastases in patients with head and neck cancer: Is there a role for 18FDG-PET?

The detection of distant metastases and second primary tumours at the time of initial evaluation changes the prognosis and influences the selection of treatment modality in patients with HNSCC. Until recently chest CT was the single most effective test to screen for distant metastases in HNSCC patients. In this observational cohort study we prospectively compared the yield of whole body 18FDG-PET and chest CT to detect distant metastases and synchronous primary tumours. The results of whole body 18FDG-PET and chest CT were analysed in 34 consecutive HNSCC patients with previously established risk factors for the presence of distant metastases. Four patients were diagnosed with distant metastases or second primary tumours: CT as well as 18FDG-PET identified one patient with lung metastases and another with primary lung cancer. In addition, 18FDG-PET detected second primary tumours in two patients (hepatocellular carcinoma and abdominal adenocarcinoma). However increased uptake sites at 18FDG-PET in lung, liver and pelvis in five patients were not confirmed by other imaging modalities. The added value of whole body 18FDG-PET versus chest CT was to identify unknown malignancy in 6% of the patients. Confirmation of positive 18FDG-PET findings is feasible and necessary