Comprehensive Catalog of Variants Potentially Associated with Hidradenitis Suppurativa, Including Newly Identified Variants from a Cohort of 100 Patients.

Hidradenitis suppurativa (HS) is a chronic skin disease characterized by painful, recurrent abscesses, nodules, and scarring, primarily in skin folds. The exact causes of HS are multifactorial, involving genetic, hormonal, and environmental factors. It is associated with systemic diseases such as metabolic syndrome and inflammatory bowel disease.

Layer myocardial strain is the most heritable echocardiographic trait.

Aims: Myocardial deformation assessed by strain analysis represents a significant advancement in our assessment of cardiac mechanics. However, whether this variable is genetically heritable or whether all/most of its variability is related to environmental factors is currently unknown. We sought to determine the heritability of echocardiographically determined cardiac mechanics indices in a population setting.

Shared Heritability of Blood Pressure and Pulse Wave Velocity: Insights From the STANISLAS Cohort.

Background: Pulse wave velocity (PWV) is a marker of arterial stiffness, which is intrinsically highly correlated with blood pressure (BP). However, the interplay of PWV and BP heritability has not been extensively studied. This study aimed to estimate the heritability of PWV and BP and determine the genetic correlation between PWV and BP.

Association and performance of polygenic risk scores for breast cancer among French women presenting or not a familial predisposition to the disease.

Background: Three partially overlapping breast cancer polygenic risk scores (PRS) comprising 77, 179 and 313 SNPs have been proposed for European-ancestry women by the Breast Cancer Association Consortium (BCAC) for improving risk prediction in the general population. However, the effect of these SNPs may vary from one country to another and within a country because of other factors.

Objective: To assess their associated risk and predictive performance in French women from (1) the CECILE population-based case-control study, (2) BRCA1 or BRCA2 (BRCA1/2) pathogenic variant (PV) carriers from the GEMO study, and (3) familial breast cancer cases with no BRCA1/2 PV and unrelated controls from the GENESIS study.

Identification of risk loci for primary aldosteronism in genome-wide association studies.

Primary aldosteronism affects up to 10% of hypertensive patients and is responsible for treatment resistance and increased cardiovascular risk. Here we perform a genome-wide association study in a discovery cohort of 562 cases and 950 controls and identify three main loci on chromosomes 1, 13 and X; associations on chromosome 1 and 13 are replicated in a second cohort and confirmed by a meta-analysis involving 1162 cases and 3296 controls. The association on chromosome 13 is specific to men and stronger in bilateral adrenal hyperplasia than aldosterone producing adenoma.

Fatty acid desaturase genetic variations and dietary omega-3 fatty acid intake associate with arterial stiffness.

Aims: Long-chain polyunsaturated fatty acids (PUFAs) generate diverse bioactive lipid mediators, which tightly regulate vascular inflammation. The effects of omega-3 PUFA supplementation in cardiovascular prevention however remain controversial. In addition to direct dietary intake, fatty acid desaturases (FADS) determine PUFA levels.

Weak Association Between Genetic Markers of Hyperuricemia and Cardiorenal Outcomes: Insights From the STANISLAS Study Cohort With a 20-Year Follow-Up.

Background Hyperuricemia is associated with poor cardiovascular outcomes, although it is uncertain whether this relationship is causal in nature. This study aimed to: (1) assess the heritability of serum uric acid (SUA) levels, (2) conduct a genome-wide association study on SUA levels, and (3) investigate the association between certain single-nucleotide polymorphisms and target organ damage. Methods and Results The STANISLAS (Suivi Temporaire Annuel Non-Invasif de la Santé des Lorrains Assurés Sociaux) study cohort is a single-center longitudinal cohort recruited between 1993 and 1995 (visit 1), with a last visit (visit 4 [V4]) performed ≈20 years apart.

PIntMF: Penalized Integrative Matrix Factorization method for multi-omics data.

Motivation: It is more and more common to perform multi-omics analyses to explore the genome at diverse levels and not only at a single level. Through integrative statistical methods, multi-omics data have the power to reveal new biological processes, potential biomarkers and subgroups in a cohort. Matrix factorization (MF) is an unsupervised statistical method that allows a clustering of individuals, but also reveals relevant omics variables from the various blocks.

Impact of natriuretic peptide polymorphisms on diastolic and metabolic function in a populational cohort: insights from the STANISLAS cohort.

Aims: Elevated brain natriuretic peptide (BNP) and the N-terminal fragment of its pro-hormone (NT-proBNP) have become established biomarkers for heart failure and are associated with cardiovascular morbidity and mortality. Investigating sources of inter-individual heterogeneity, particularly genetic factors, could help better identify patients at risk of future cardiovascular disease. The aim of this study was to estimate the heritability of circulating NT-proBNP levels, to perform a genome-wide association study (GWAS) and gene-candidate analysis focused on NPPB-NPPA genes on these levels, and to examine their association with cardiovascular or metabolic outcomes.

Heritability of a resting heart rate in a 20-year follow-up family cohort with GWAS data: Insights from the STANISLAS cohort.

Background: The association between resting heart rate (HR) and cardiovascular outcomes, especially heart failure, is now well established. However, whether HR is mainly an integrated marker of risk associated with other features, or rather a genetic origin risk marker, is still a matter for debate. Previous studies reported a heritability ranging from 14% to 65%.

Region-specific expression of young small-scale duplications in the human central nervous system.

Background: The duplication of genes is one of the main genetic mechanisms that led to the gain in complexity of biological tissue. Although the implication of duplicated gene expression in brain evolution was extensively studied through comparisons between organs, their role in the regional specialization of the adult human central nervous system has not yet been well described.

Results: Our work explored intra-organ expression properties of paralogs through multiple territories of the human central nervous system (CNS) using transcriptome data generated by the Genotype-Tissue Expression (GTEx) consortium.

Genome-wide haplotype association study in imaging genetics using whole-brain sulcal openings of 16,304 UK Biobank subjects.

Neuroimaging-genetics cohorts gather two types of data: brain imaging and genetic data. They allow the discovery of associations between genetic variants and brain imaging features. They are invaluable resources to study the influence of genetics and environment in the brain features variance observed in normal and pathological populations.

Exploring the Link Between Additive Heritability and Prediction Accuracy From a Ridge Regression Perspective.

Genome-Wide Association Studies (GWAS) explain only a small fraction of heritability for most complex human phenotypes. Genomic heritability estimates the variance explained by the SNPs on the whole genome using mixed models and accounts for the many small contributions of SNPs in the explanation of a phenotype. This paper approaches heritability from a machine learning perspective, and examines the close link between mixed models and ridge regression.

Circulating plasma proteins and new-onset diabetes in a population-based study: proteomic and genomic insights from the STANISLAS cohort.

Objective: Determining the factors associated with new-onset pre-diabetes and type 2 diabetes mellitus (T2D) is important for improving the current prevention strategies and for a better understanding of the disease.

Design: To study the factors (clinical, circulating protein and genetic) associated with new onset pre-diabetes and T2D in an initially healthy (without diabetes) populational familial cohort with a long follow-up (STANISLAS cohort).

Methods: A total of 1506 participants attended both the visit 1 and visit 4, separated by ≈20 years.

PCSK9 Protein and rs562556 Polymorphism Are Associated With Arterial Plaques in Healthy Middle-Aged Population: The STANISLAS Cohort.

Background PCSK9 (Proprotein convertase subtilisin/kexin type 9) binds low-density lipoprotein receptor, preventing its recycling. PCSK9 is a risk predictor and a biotarget in atherosclerosis. The PCSK9-rs562556 variant has been reported as a gain-of-function mutation.

Clustering and variable selection evaluation of 13 unsupervised methods for multi-omics data integration.

Recent advances in NGS sequencing, microarrays and mass spectrometry for omics data production have enabled the generation and collection of different modalities of high-dimensional molecular data. The integration of multiple omics datasets is a statistical challenge, due to the limited number of individuals, the high number of variables and the heterogeneity of the datasets to integrate. Recently, a lot of tools have been developed to solve the problem of integrating omics data including canonical correlation analysis, matrix factorization and SM.

Where are the missing gene defects in inherited retinal disorders? Intronic and synonymous variants contribute at least to 4% of CACNA1F-mediated inherited retinal disorders.

Inherited retinal disorders (IRD) represent clinically and genetically heterogeneous diseases. To date, pathogenic variants have been identified in ~260 genes. Albeit that many genes are implicated in IRD, for 30-50% of the cases, the gene defect is unknown.

Toxoplasma gondii exposure may modulate the influence of TLR2 genetic variation on bipolar disorder: a gene-environment interaction study.

Background: Genetic vulnerability to environmental stressors is yet to be clarified in bipolar disorder (BD), a complex multisystem disorder in which immune dysfunction and infectious insults seem to play a major role in the pathophysiology. Association between pattern-recognition receptor coding genes and BD had been previously reported. However, potential interactions with history of pathogen exposure are yet to be explored.

Significant correlation between a set of genetic polymorphisms and a functional brain network revealed by feature selection and sparse Partial Least Squares.

Brain imaging is increasingly recognised as an intermediate phenotype to understand the complex path between genetics and behavioural or clinical phenotypes. In this context, a first goal is to propose methods to identify the part of genetic variability that explains some neuroimaging variability. Classical univariate approaches often ignore the potential joint effects that may exist between genes or the potential covariations between brain regions.

Voxelwise multivariate statistics and brain-wide machine learning using the full diffusion tensor.

In this paper, we propose to use the full diffusion tensor to perform brain-wide score prediction on diffusion tensor imaging (DTI) using the log-Euclidean framework., rather than the commonly used fractional anisotropy (FA). Indeed, scalar values such as the FA do not capture all the information contained in the diffusion tensor.