Insights into Male Androgenetic Alopecia: Differential Gene Expression Profiling of Plucked Hair Follicles and Integration with Genetic Data

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Genome-wide association study of borderline personality disorder reveals genetic overlap with the bipolar disorder, schizophrenia and major depression

Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of Bipolar Disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case-control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was: (i) to detect genes and gene-sets involved in BOR; and (ii) to investigate the genetic overlap with BIP. As there is considerable genetic overlap between BIP, Major Depression (MDD) and Schizophrenia (SCZ) and a high comorbidity of BOR and MDD, we also analyzed the genetic overlap of BOR with SCZ and MDD. GWAS, gene-based tests,and gene-set-analyses were performed in 998 BOR patients and 1,545 controls. LD score regression was used to detect genetic overlap between BOR and these disorders. Single marker analysis revealed no significant association after correction for multiple testing. Genebased analysis yielded two significant genes: DPYD (p=4.42x10-7) and PKP4 (p=8.67x10-7); and gene-set-analysis yielded a significant finding for exocytosis (GO:0006887, pFDR=0.019). Prior studies have implicated DPYD, PKP4 and exocytosis in BIP and SCZ. The most notable finding of the present study was the genetic overlap of BOR with BIP (rg=0.28 [p=2.99x10-3]), SCZ (rg=0.34 [p=4.37x10-5]), and MDD (rg=0.57 [p=1.04x10-3]). Our study is the first to demonstrate that BOR overlaps with BIP, MDD and SCZ on the genetic level. Whether this is confined to transdiagnostic clinical symptoms should be examined in future studies

Genetic Contribution to Alcohol Dependence: Investigation of a Heterogeneous German Sample of Individuals with Alcohol Dependence, Chronic Alcoholic Pancreatitis, and Alcohol-Related Cirrhosis

The present study investigated the genetic contribution to alcohol dependence (AD) using genome-wide association data from three German samples. These comprised patients with: (i) AD; (ii) chronic alcoholic pancreatitis (ACP); and (iii) alcohol-related liver cirrhosis (ALC). Single marker, gene-based, and pathway analyses were conducted. A significant association was detected for the ADH1B locus in a gene-based approach (puncorrected = 1.2 × 10−6; pcorrected = 0.020). This was driven by the AD subsample. No association with ADH1B was found in the combined ACP + ALC sample. On first inspection, this seems surprising, since ADH1B is a robustly replicated risk gene for AD and may therefore be expected to be associated also with subgroups of AD patients. The negative finding in the ACP + ALC sample, however, may reflect genetic stratification as well as random fluctuation of allele frequencies in the cases and controls, demonstrating the importance of large samples in which the phenotype is well assessed

ISL1 is a major susceptibility gene for classic bladder exstrophy and a regulator of urinary tract development.

Previously genome-wide association methods in patients with classic bladder exstrophy (CBE) found association with ISL1, a master control gene expressed in pericloacal mesenchyme. This study sought to further explore the genetics in a larger set of patients following-up on the most promising genomic regions previously reported. Genotypes of 12 markers obtained from 268 CBE patients of Australian, British, German Italian, Spanish and Swedish origin and 1,354 ethnically matched controls and from 92 CBE case-parent trios from North America were analysed. Only marker rs6874700 at the ISL1 locus showed association (p = 2.22 × 10-08). A meta-analysis of rs6874700 of our previous and present study showed a p value of 9.2 × 10-19. Developmental biology models were used to clarify the location of ISL1 activity in the forming urinary tract. Genetic lineage analysis of Isl1-expressing cells by the lineage tracer mouse model showed Isl1-expressing cells in the urinary tract of mouse embryos at E10.5 and distributed in the bladder at E15.5. Expression of isl1 in zebrafish larvae staged 48 hpf was detected in a small region of the developing pronephros. Our study supports ISL1 as a major susceptibility gene for CBE and as a regulator of urinary tract development

Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation

Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death. Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups. To further define the genetic basis of atrial fibrillation, we performed large-scale, trans-ancestry meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 17,931 individuals with atrial fibrillation and 115,142 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,346 cases and 132,086 referents. We identified 12 new genetic loci that exceeded genome-wide significance, implicating genes involved in cardiac electrical and structural remodeling. Our results nearly double the number of known genetic loci for atrial fibrillation, provide insights into the molecular basis of atrial fibrillation, and may facilitate the identification of new potential targets for drug discovery

High quality genome assembly and annotation (v1) of the eukaryotic terrestrial microalga Coccomyxa viridis SAG 216-4

Unicellular green algae of the genus Coccomyxa are recognized for their worldwide distribution and ecological versatility. Most species described to date live in close association with various host species, such as in lichen associations. However, little is known about the molecular mechanisms that drive such symbiotic lifestyles. We generated a high-quality genome assembly for the lichen photobiont Coccomyxa viridis SAG 216-4 (formerly C. mucigena). Using long-read PacBio HiFi and Oxford Nanopore Technologies in combination with chromatin conformation capture (Hi-C) sequencing, we assembled the genome into 21 scaffolds with a total length of 50.9 Mb, an N50 of 2.7 Mb and a BUSCO score of 98.6%. While 19 scaffolds represent full-length nuclear chromosomes, two additional scaffolds represent the mitochondrial and plastid genomes. Transcriptome-guided gene annotation resulted in the identification of 13,557 protein-coding genes, of which 68% have annotated PFAM domains and 962 are predicted to be secreted

Assessing the suitability of formalin-fixed paraffin-embedded (FFPE) tissue for genome-wide association studies (GWAS)

Objective The power of genome-wide association studies (GWAS) to identify common disease variants depends primarily on the number of included samples. The availability of formalin-fixed paraffin-embedded (FFPE) samples in pathology institutes provides a valuable resource for GWAS, but the use of this material poses significant challenges. To explore the suitability of utilizing FFPE tissue for GWAS, we analysed the genotyping concordance between corresponding FFPE and blood samples. We evaluated both microarray technology and low-coverage whole-genome sequencing (lcWGS) to determine whether there were differences between genotyping methods. Results In our concordance study, FFPE tissue showed high recall and precision values across both genotyping methods when compared to matched blood samples for single nucleotide polymorphisms. This demonstrates that FFPE samples are suitable for GWAS and that both methods are viable options for genotyping. However, microarray technology outperformed lcWGS, as evidenced by significantly higher recall ( p  = 0.005) and precision ( p  = 0.003) values. This, together with the lower cost of genotyping and computational efficiency, makes microarray technology currently the superior method for GWAS using FFPE tissue. Nevertheless, lcWGS has shown reliable results and holds the potential to provide more comprehensive and unbiased genetic variant analysis across diverse populations in the future. Our results show that the large number of FFPE samples stored in pathology institutes can significantly increase the power of future GWAS.Open Access funding enabled and organized by Projekt DEAL.Philipps-Universität Marburg (1009