The Genetic Architecture of Gene Expression in Peripheral Blood.

We analyzed the mRNA levels for 36,778 transcript expression traits (probes) from 2,765 individuals to comprehensively investigate the genetic architecture and degree of missing heritability for gene expression in peripheral blood. We identified 11,204 cis and 3,791 trans independent expression quantitative trait loci (eQTL) by using linear mixed models to perform genome-wide association analyses. Furthermore, using information on both closely and distantly related individuals, heritability was estimated for all expression traits. Of the set of expressed probes (15,966), 10,580 (66%) had an estimated narrow-sense heritability (h2) greater than zero with a mean (median) value of 0.192 (0.142). Across these probes, on average the proportion of genetic variance explained by all eQTL (hCOJO2) was 31% (0.060/0.192), meaning that 69% is missing, with the sentinel SNP of the largest eQTL explaining 87% (0.052/0.060) of the variance attributed to all identified cis- and trans-eQTL. For the same set of probes, the genetic variance attributed to genome-wide common (MAF > 0.01) HapMap 3 SNPs (hg2) accounted for on average 48% (0.093/0.192) of h2. Taken together, the evidence suggests that approximately half the genetic variance for gene expression is not tagged by common SNPs, and of the variance that is tagged by common SNPs, a large proportion can be attributed to identifiable eQTL of large effect, typically in cis. Finally, we present evidence that, compared with a meta-analysis, using individual-level data results in an increase of approximately 50% in power to detect eQTL.

Patients' preferences for headache acute and preventive treatment.

BACKGROUND: We aimed to explore patients' preferences for headache treatments with a self-administered questionnaire including the Q-No questionnaire for nocebo. METHODS: Questionnaires from 514 outpatients naïve to neurostimulation and monoclonal antibodies were collected. RESULTS: Patients assessed that the efficacy of a treatment is more important than safety or route of administration. They preferred to use an external neurostimulation device for both acute (67.1%) and preventive treatment (62.8%). Most patients preferred to take a pill (86%) than any other drug given parenterally for symptomatic pharmaceutical treatment. For preventive pharmaceutical treatment, most patients preferred to take a pill once per day (52%) compared to an injection either subcutaneously or intravenously each month (9% and 4%), or three months (15% and 11%). 56.6% of all participants scored more than 15 in Q-No questionnaire indicating potential nocebo behaviors that contributed significantly in their choices. CONCLUSION: These patient preferences along with efficacy and safety data may help physicians better choose the right treatment for the right person.

SPHN - The Swiss Aging Citizen Reference (SACR).

In Switzerland by 2045, we expect 2.7 Mio citizens aged 65+ of whom 1.0 Mio. aged 80+. A priority and focus of personalized health research is therefore aging biology to extend healthy life expectancy. Novel molecular and imaging features will emerge as candidate targets for risk prediction and screening of chronic diseases. It is of utmost importance to test the clinical and public health utility of candidate biomarkers evolving from this research in citizen reference cohorts. We will build a Swiss Aging Citizen Reference (SACR), a testable and scalable reference cohort offering interoperable, searchable, and accessible data. 1000 participants from existing Swiss citizen cohorts will be combined and analyzed for DNA methylation and MRI brain imaging. SACR will serve as a testbed for clinical and public health utility of candidate biomarkers. As for a proof-of-concept study, we will conduct an agnostic search for structural and functional brain features associated with epigenetic aging acceleration to examine the potential of epigenetic age acceleration as the intermediate aging biomarker and to better understand the aging mechanism in brain.