University of Ioannina

About: University of Ioannina is a education organization based out in Ioannina, Greece. It is known for research contribution in the topics: Population & Large Hadron Collider. The organization has 7654 authors who have published 20594 publications receiving 671560 citations. The organization is also known as: Panepistimio Ioanninon.

Implications of Small Effect Sizes of Individual Genetic Variants on the Design and Interpretation of Genetic Association Studies of Complex Diseases

Abstract: Accumulated evidence from searching for candidate gene-disease associations of complex diseases can offer some insights as the field moves toward discovery-oriented approaches with massive genome-wide testing. Metaanalyses of 50 non–human lymphocyte antigen gene-disease associations with documented overall statistical significance (752 studies) show summary odds ratios with a median of 1.43 (interquartile range, 1.28–1.65). Many different biases may operate in this field, for both single studies and meta-analyses, and these biases could invalidate some of these seemingly ‘‘validated’’ associations. Studies with a sample size of >500 show a median odds ratio of only 1.15. The median sample size required to detect the observed summary effects in each population addressed in the 752 studies is estimated to be 3,535 (interquartile range, 1,936–9,119 for cases and controls combined). These estimates are steeply inflated in the presence of modest bias. Population heterogeneity, as well as gene-gene and gene-environment interactions, could steeply increase these estimates and may be difficult to address even by very large biobanks and observational cohorts. The one visible solution is for a large number of teams to join forces on the same research platforms. These collaborative studies ideally should be designed up front to also assess more complex gene-gene and gene-environment interactions.

The association between common vitamin D receptor gene variations and osteoporosis: a participant-level meta-analysis

Abstract: This multicenter, prospective study involving 26 242 participants examined associations between vitamin D receptor polymorphisms (Cdx2 promoter, FokI, BsmI, ApaI, and TaqI), bone mineral density (B...

Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

Abstract: High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used -1/4155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.