The major anxiety disorders (ANX; including generalized anxiety disorder, panic disorder and phobias) are highly prevalent, often onset early and cause substantial global disability. Although distinct in their clinical presentations, they probably represent differential expressions of a dysregulated threat-response system. Here, we present a genome-wide association meta-analysis comprising 122,341 European ancestry ANX cases and 729,881 controls. We identified 58 independent genome-wide significant risk variants and 66 genes with robust biological support. In an independent sample of 1,175,012 self-report ANX cases and 1,956,379 controls, 51 out of the 58 associations replicated. As predicted by twin studies, we found substantial genetic correlation between ANX and depression, neuroticism and other internalizing phenotypes. Follow-up analyses demonstrated enrichment in all major brain regions and highlighted GABAergic signaling as one potential mechanism implicated in ANX genetic risk. These results advance our understanding of the genetic architecture of ANX and prioritize genes for functional follow-up studies.

Unicellular green algae of the genus Coccomyxa are recognized for their worldwide distribution and ecological versatility. Coccomyxa elongata is a freshwater species of the Coccomyxa simplex clade, which also includes lichen symbionts. To facilitate future molecular and phylogenomic studies of this versatile clade of algae, we generated a high-quality genome assembly for C. elongata Chodat & Jaag SAG 216-3b within the framework of the Biodiversity Genomics Center Cologne (BioC2) initiative. A combination of long-read PacBio HiFi and Oxford Nanopore Technologies with chromatin conformation capture (Hi-C) sequencing led to the assembly of the genome into 21 scaffolds with a total length of 51.4 Mb and an N50 of 2.8 Mb. Nineteen of the scaffolds represent highly complete nuclear chromosomes delimited by telomeric repeats, while the two additional scaffolds represent the mitochondrial and plastid genomes. Transcriptome-guided gene annotation resulted in the identification of 14,811 protein-coding genes, of which 61% have annotated protein family domains and 841 are predicted to be secreted. Benchmarking universal single-copy orthologs analysis against the Chlorophyta database identified a total of 1,494 (98.4%) complete gene models, suggesting a highly complete genome annotation.

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.

IMPORTANCE: Postoperative delirium (POD) is a multietiological condition and affects 20% of older surgical patients. It is associated with poor clinical outcome and increased mortality. OBJECTIVE: We aimed to develop and validate a risk prediction algorithm for POD based on a multimodal biomarker database exploiting preoperative data (predisposing factors) and procedural factors as well as perioperative molecular changes associated with POD (precipitating factors). DESIGN: BioCog is a prospective cohort study conducted from November 2014 to April 2017. Patients were followed up for seven postoperative days after surgery for POD. Gradient-boosted trees (GBT) with nested cross-validation was used for POD prediction. SETTING: Patients aged ≥65 years were enrolled at the anesthesiologic departments of two tertiary care centers. EXPOSURE: All patients underwent surgery with an expected duration of at least 60min. Clinical, neuropsychological, neuroimaging data and blood were collected and clinically well established as well as non-established biomarkers (e.g., gene expression profiling) were measured pre- and postoperatively. MAIN OUTCOME: POD according to DSM 5 until the seventh postoperative day RESULTS: 184 of 929 (20%) patients experienced POD. A GBT algorithm using both preoperative data, characteristics of the intervention and postoperative changes in laboratory parameters achieved the highest area under the curve (0.83, [0.79; 0.86]) with a Brier score of 0.12 (0.12; 0.13). CONCLUSIONS AND RELEVANCE: Models combining predisposing factors with precipitating factors predict POD best. Non-routine laboratory data provide useful information for POD risk prediction, providing relevant results for future studies on the molecular factors of POD. In addition, possibly relevant molecular mechanisms contributing to the development of POD were identified, mostly indicating a dysregulated postoperative immune response. This study constitutes the basis for future hypothesis-driven analyses or implementation of prediction expert system for clinical practice. ### Competing Interest Statement Georg Winterer is currently licensing a Class IIa medical device (web-based software tool for risk prediction of POD and POCD in clinical practice). Dr. Winterer is CEO of PharmaImage Biomarker Solutions GmbH Berlin (Germany) and President of its subsidiary Pharmaimage Biomarkers Incl. (Cambridge, MA, USA). Dr. Spies, Dr. Winterer, Dr. Boraschi, Dr. Dschietzig, Dr. Kuehn, Dr. Nuernberg, Dr. Pischon, Dr. Pietzsch, Dr. Slooter, Dr. Stamatakis, Dr. Weber, report grants from the European Commission during the conduct of the study. Dr. Winterer reports grants from the Deutsche Forschungsgemeinschaft (DFG)/German Research Society and from the German Ministry of Health. Dr. Spies reports grants from DFG/German Research Society, Einstein Foundation Berlin, Deutsches Zentrum fuer Luft- und Raumfahrt e.V. (DLR)/German Aerospace Center, Projekttraeger im DLR/Project Management Agency, Gemeinsamer Bundesausschuss (GBA)/Federal Joint Committee, inneruniversity grants, Stifterverband/Non-Profit Society Promoting Science and Education, European Society of Anesthesiology and Intensive Care, BMWI - Federal Ministry of Economic Affairs and Climate Action, Dr. F. Koehler Chemie GmbH, Sintetica GmbH, Max-Planck-Gesellschaft zur Foerderung der Wissenschaft e.V., Metronic, BMBF - Federal Ministry of Education and Research, Robert Koch Institute and payments by Georg Thieme Verlag, board activity for Prothor, Takeda Pharmaceutical Company Ltd., Lynx Health Science GmbH, AWMF (Association of the Scientific Medical Societies in Germany), DFG, Deutsche Akademie der Naturforscher Leopoldina e.V. (German National Academy of Sciences Leopoldina), Berliner Medizinische Gesellschaft, European Society of Intensive Care Medicine (ESICM), European Society of Anaesthesiology and Intensive Care (ESAIC), Deutsche Gesellschaft fuer Anaesthesiologie und Intensivmedizin (DGAI)/German Society of Anaesthesiology and Intensive Care Medicine, German Interdisciplinary Association for Intensive Care and Emergency Medicine (DIVI) as well as patents 15753 627.7, PCT/EP 2015/067731, 3 174 588, 10 2014 215 211.9, 10 2018 114 364.8, 10 2018 110 275.5, 50 2015 010 534.8, 50 2015 010 347.7, 10 2014 215 212.7. Gunnar Lachmann and Maria Heinrich report grants from the BIH Charite Clinician Scientist Program during conduct of the study. Dr. Dschietzig reports personal fees from Immundiagnostik AG during the conduct of the study. Dr. Lammers-Lietz and Anton Wiehe report personal fees from Pharmaimage Biomarker Solutions GmbH during the conduct of the study. Dr. Lachmann reports personal fees from Sobi, the University of Zurich and Thieme outside the submitted work. Dr. Wolf receives fees from the Kompetenz-Centrum Qualitaetssicherung. Dr. Stamatakis reports funding from Stephen Erskine Fellowship from Queens' College of the University of Cambridge, UK outside the BioCog study. Dr. Bresser reports funding from Alzheimer Nederland outside of the study. Dr. Gallinat received funding from the German Research Foundation (DFG), Federal Ministry of Education and Research (BMBF) and received payment for five lectures and presentations with about 1.500 euro per presentation sponsored by Lundbeck, Janssen-Cilag and Boehringer. Dr. Heilmann-Heimbach receives personal fees from Life&Brain GmbH. None of the other authors have a conflict of interest to declare. ### Funding Statement The research leading to these results has received funding from the European Union Seventh Framework Program [FP7/2007-2013] under grant agreement no. 602461. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committees of the Charite-Universitaetsmedizin Berlin, Germany, (EA2/092/14) and University Medical Center Utrecht (UMC), Utrecht University, Netherlands, (14-469) gave ethical approval of this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Due to the protection of intellectual property, machine learning algorithms will not be made publicly available, but can be obtained from Dr. Winterer (georg.winterer@pi-pharmaimage.com) after signing a confidentiality agreement. Participant data may be made available upon request following publication to researchers who provide a methodologically sound proposal in accordance with applicable legal and regulatory restrictions. Proposals for data analysis must be directed to both claudia.spies@charite.de and georg.winterer@pi-pharmaimage.com. To gain access, requesting researchers will need to sign a data access agreement. Analyses will be limited to those approved in appropriate ethics and governance arrangements. All study documents which do not identify individuals (e.g. study protocol, informed consent form) will be freely available on request.

Due to methodological reasons, the X-chromosome has not been featured in the major genome-wide association studies on Alzheimer's Disease (AD). To finally address this and better characterize the genetic landscape of AD, we performed an in-depth X-Chromosome-Wide Association Study (XWAS) in 115,841 AD cases or AD proxy cases, including 52,214 clinically-diagnosed AD cases, and 613,671 controls. We considered three approaches to account for the different X-chromosome inactivation (XCI) states in females, i.e. random XCI, skewed XCI, and escape XCI. We did not detect any genome-wide significant signals (P ≤ 5 × 10−8) but identified four X-chromosome-wide significant loci (P ≤ 1.7 × 10−6). Two signals locate in theFRMPD4andDMDgenes, while the two others are more than 300 kb away from the closest protein coding genesNLGN4XandGRIA3. Overall, this XWAS found no common genetic risk factors for AD on the non-pseudoautosomal region of the X-chromosome, but it identified suggestive signals warranting further investigations.

BACKGROUND:Short anagen hair (SAH) is a rare paediatric hair disorder characterized by a short anagen phase, an inability to grow long scalp hair and a negative psychological impact. The genetic basis of SAH is currently unknown. OBJECTIVES:To perform molecular genetic investigations in 48 individuals with a clinical phenotype suggestive of SAH to identify, if any, the genetic basis of this condition. METHODS:Exome sequencing was performed in 27 patients diagnosed with SAH or with a complaint of short, nongrowing hair. The cohort was screened for variants with a minor allele frequency (MAF) < 5% in the general population and a Combined Annotation Dependent Depletion (CADD) score > 15, to identify genes whose variants were enriched in this cohort. Sanger sequencing was used for variant validation and screening of 21 additional individuals with the same clinical diagnosis and their relatives. Genetic association testing of SAH-related variants for male pattern hair loss (MPHL) was performed using UK Biobank data. RESULTS:Analyses revealed that 20 individuals (42%) carried mono- or biallelic pathogenic variants in WNT10A. Rare WNT10A variants are associated with a phenotypic spectrum ranging from no clinical signs to severe ectodermal dysplasia. A significant association was found between WNT10A and SAH, and this was mostly observed in individuals with light-coloured hair and regression of the frontoparietal hairline. Notably, the most frequent variant in the cohort [c.682T>A;p.(Phe228Ile)] was in linkage disequilibrium with four common WNT10A variants, all of which have a known association with MPHL. Using UK Biobank data, our analyses showed that c.682T>A;p.(Phe228Ile) and one other variant identified in the SAH cohort are also associated with MPHL, and partially explain the known associations between WNT10A and MPHL. CONCLUSIONS:Our results suggest that WNT10A is associated with SAH and that SAH has a genetic overlap with the common phenotype MPHL. The presumed shared biologic effect of WNT10A variants in SAH and MPHL is a shortening of the anagen phase. Other factors, such as modifier genes and sex, may also play a role in the clinical manifestation of hair phenotypes associated with the WNT10A locus.

BACKGROUND:Given the great interest in identifying reliable predictors of the response to antidepressant drugs, the present study investigated whether polygenic scores (PGS) for Major Depressive Disorder (MDD) and antidepressant treatment response (ADR) were related to the complex trait of antidepressant response in the Early Medication Change (EMC) cohort. METHODS:In this secondary analysis of the EMC trial (N = 889), 481 MDD patients were included and compared to controls from a population-based cohort. Patients were treated over eight weeks within a pre-defined treatment-algorithm. We investigated patients' genetic variation associated with MDD and ADR, using PGS and examined the association of PGS with treatment outcomes (early improvement, response, remission). Additionally, the influence of two cytochrome P450 drug-metabolizing enzymes (CYP2C19, CYP2D6) was determined. RESULTS:PGS for MDD was significantly associated with disorder status (NkR2 = 2.48 %, p < 1*10-12), with higher genetic burden in EMC patients compared to controls. The PGS for ADR did not explain remission status. The PGS for MDD and ADR were also not associated with treatment outcomes. In addition, there were no effects of common CYP450 gene variants on ADR. LIMITATIONS:The study was limited by variability in the outcome parameters due to differences in treatment and insufficient sample size in the used ADR genome-wide association study (GWAS). CONCLUSIONS:The present study confirms a polygenic contribution to MDD burden in the EMC patients. Larger GWAS with homogeneity in antidepressant treatments are needed to explore the genetic variation associated with ADR and realize the potential of PGS to contribute to specific response subtypes.

Resilience is the capacity to adapt to stressful life events. As such, this trait is associated with physical and mental functions and conditions. Here, we aimed to identify the genetic factors contributing to shape resilience. We performed variant- and gene-based meta-analyses of genome-wide association studies from six German cohorts (N = 15822) using the 11-item version of the Resilience Scale (RS-11) as outcome measure. Variant- and gene-level results were combined to explore the biological context using network analysis. In addition, we conducted tests of correlation between RS-11 and the polygenic scores (PGSs) for 12 personality and mental health traits in one of these cohorts (PROCAM-2, N = 3879). The variant-based analysis found no signals associated with resilience at the genome-wide level (p < 5 × 10−8), but suggested five genomic loci (p < 1 × 10−5). The gene-based analysis identified three genes (ROBO1, CIB3 and LYPD4) associated with resilience at genome-wide level (p < 2.48 × 10−6) and 32 potential candidates (p < 1 × 10−4). Network analysis revealed enrichment of biological pathways related to neuronal proliferation and differentiation, synaptic organization, immune responses and vascular homeostasis. We also found significant correlations (FDR < 0.05) between RS-11 and the PGSs for neuroticism and general happiness. Overall, our observations suggest low heritability of resilience. Large, international efforts will be required to uncover the genetic factors that contribute to shape trait resilience. Nevertheless, as the largest investigation of the genetics of resilience in general population to date, our study already offers valuable insights into the biology potentially underlying resilience and resilience’s relationship with other personality traits and mental health.

Male-pattern hair loss (MPHL) is the most common form of hair loss in humans. Limited treatment options exist, which are not curative and vary in efficacy and invasiveness. Therapeutic and cosmetic hair growth stimulating agents that alleviate hair loss at a low risk of side effects are therefore of interest. The efficacy of hair growth-stimulating agents is mainly evaluated by hair comb tests and trichograms. These methods do not offer molecular insights, which can provide early insights into treatment response and may be useful in monitoring long-term compliance and efficacy. We propose a general concept for the molecular monitoring of hair growth stimulating agent treatment response in vivo, based on RNA and microRNA expression profiling before and during treatment. The molecular profile can be extended by individual genotype information to assess the impact of genetic constitution on treatment response. To test this methodological approach, 91 male participants with visible signs of and/or a family history of MPHL were assigned to four groups to investigate the effects of three hair growth stimulating agents versus placebo. mRNA- and microRNA-Seq was performed on plucked hair follicle samples before, after four days, and after six weeks of treatment. Genotyping was performed on DNA extracted from blood or saliva samples. Differential expression analyses identified 52 differentially expressed genes and 17 modulated pathways following treatment with the three hair growth stimulating agents. While the majority of effects were detectable after 6-week treatment, 23% of genes showed significant regulation after 4-day treatment. Integration with genetic data through pathway-based polygenic risk score analyses identified 5 associations between genetic background and treatment effects, pointing to a potential value of companion diagnostics for hair growth stimulating agents. Our data show that this molecular monitoring approach provides insights into hair growth stimulating agent treatment response as early as days within commencing treatment, and is suitable to monitor long-term treatment effects and compliance. Combined with genetic profiling, this approach may enable personalized prediction of treatment efficacy and compliance.

AbstractUp to 80 % of European men experience some degree of male-pattern hair loss (MPHL) during their lifetime. The condition is highly heritable and current treatment options are limited, emphasizing the need for a better understanding of its biological causes. In recent years, molecular genetic studies have provided significant insights into the genetic and biological causes of MPHL. This article summarizes important findings and discusses their potential for improving hair loss prediction and treatment.

Integrative analyses that incorporate different levels of ‘-omics’ data represent a powerful tool for deciphering the biological mechanisms that underlie environmental influences on mental health and disease. This Comment highlights various aspects of such multi-omics approaches, using the example of the EU-funded environMENTAL project.

BackgroundAngioedema is a rare but potentially life-threatening adverse drug reaction in patients receiving angiotensin-converting enzyme inhibitors (ACEis). Research suggests that susceptibility to ACEi-induced angioedema (ACEi-AE) involves both genetic and nongenetic risk factors. Genome- and exome-wide studies of ACEi-AE have identified the first genetic risk loci. However, understanding of the underlying pathophysiology remains limited.ObjectiveWe sought to identify further genetic factors of ACEi-AE to eventually gain a deeper understanding of its pathophysiology.MethodsBy combining data from 8 cohorts, a genome-wide association study meta-analysis was performed in more than 1000 European patients with ACEi-AE. Secondary bioinformatic analyses were conducted to fine-map associated loci, identify relevant genes and pathways, and assess the genetic overlap between ACEi-AE and other traits. Finally, an exploratory cross-ancestry analysis was performed to assess shared genetic factors in European and African-American patients with ACEi-AE.ResultsThree genome-wide significant risk loci were identified. One of these, located on chromosome 20q11.22, has not been implicated previously in ACEi-AE. Integrative secondary analyses highlighted previously reported genes (BDKRB2 [bradykinin receptor B2] and F5 [coagulation factor 5]) as well as biologically plausible novel candidate genes (PROCR [protein C receptor] and EDEM2 [endoplasmic reticulum degradation enhancing alpha-mannosidase like protein 2]). Lead variants at the risk loci were found with similar effect sizes and directions in an African-American cohort.ConclusionsThe present results contributed to a deeper understanding of the pathophysiology of ACEi-AE by (1) providing further evidence for the involvement of bradykinin signaling and coagulation pathways and (2) suggesting, for the first time, the involvement of the fibrinolysis pathway in this adverse drug reaction. An exploratory cross-ancestry comparison implicated the relevance of the associated risk loci across diverse ancestries.

Primary yolk sac tumor (YST) of the liver is uncommon disease with less than 15 cases reported worldwide and is often misdiagnosed as HCC. Therefore, in-depth molecular and histological characterization of YST and development of representative models are essential for better diagnosis and development of patient-specific therapies.

Bees are major pollinators of flowering plants and thus are important ecosystem service providers for natural habitats and crops. Evolution led to a wide range of adaptations in behaviors, morphology and ecological traits. Many plants rely on specialized bee species for pollination events, and so this interdependence can make them increasingly vulnerable to ongoing threats of habitat loss and pesticide exposure. Studying the genomes of bee species across different life histories and ecological specializations can help understand the evolution of these traits more generally, but also inform conservation efforts for Camptopoeum friesei specifically.Here, we present the reference genome of the solitary bee Camptopoeum friesei (Arthropoda; Insecta; Hymenoptera; Andrenidae).C. friesei is highly dependent on steppe habitats where it nests in saline soils. Further, it is highly specialized (oligolectic) on a few Asteraceae: Centaurea and Cirsium , in particular on Centaurea stoebe . As a consequence of its high specialization level, it is of its ecological niche with an extremely scattered and rare habitat, C. friesei is highly threatened in central Europe, albeit local aggregations can be rich in individuals.The high-quality genome assembly for the colourful bee Camptopoeum friesei was generated using long-read PacBio HiFi in combination with chromatin conformation capture (Hi-C) sequencing. The genome spans 367.7 megabases (Mb), N50 of 25.2 Mb. The majority of the assembly is scaffolded into 10 chromosomes and harbours ∼40% repeats.Species taxonomy Eukaryota; Opisthokonta; Metazoa; Eumetazoa; Bilateria; Protostomia; Ecdysozoa; Panarthropoda; Arthropoda; Mandibulata; Pancrustacea; Hexapoda; Insecta; Dicondylia; Pterygota; Neoptera; Endopterygota; Hymenoptera; Apocrita; Aculeata; Apoidea; Anthophila; Andrenidae; Panurginae; Panurgini; Camptopoeum friesei [Mocsáry, 1894][1] (NCBI:txid2918745)### Competing Interest StatementThe authors have declared no competing interest. [1]: #ref-29

Importance:An estimated 40% of dementia is potentially preventable by modifying 12 risk factors throughout the life course. However, robust evidence for most of these risk factors is lacking. Effective interventions should target risk factors in the causal pathway to dementia. Objective:To comprehensively disentangle potentially causal aspects of modifiable risk factors for Alzheimer disease (AD) to inspire new drug targeting and improved prevention. Design, Setting, and Participants:This genetic association study was conducted using 2-sample univariable and multivariable mendelian randomization. Independent genetic variants associated with modifiable risk factors were selected as instrumental variables from genomic consortia. Outcome data for AD were obtained from the European Alzheimer & Dementia Biobank (EADB), generated on August 31, 2021. Main analyses were conducted using the EADB clinically diagnosed end point data. All analyses were performed between April 12 and October 27, 2022. Exposures:Genetically determined modifiable risk factors. Main Outcomes and Measures:Odds ratios (ORs) and 95% CIs for AD were calculated per 1-unit change of genetically determined risk factors. Results:The EADB-diagnosed cohort included 39 106 participants with clinically diagnosed AD and 401 577 control participants without AD. The mean age ranged from 72 to 83 years for participants with AD and 51 to 80 years for control participants. Among participants with AD, 54% to 75% were female, and among control participants, 48% to 60% were female. Genetically determined high-density lipoprotein (HDL) cholesterol concentrations were associated with increased odds of AD (OR per 1-SD increase, 1.10 [95% CI, 1.05-1.16]). Genetically determined high systolic blood pressure was associated with increased risk of AD after adjusting for diastolic blood pressure (OR per 10-mm Hg increase, 1.22 [95% CI, 1.02-1.46]). In a second analysis to minimize bias due to sample overlap, the entire UK Biobank was excluded from the EADB consortium; odds for AD were similar for HDL cholesterol (OR per 1-SD unit increase, 1.08 [95% CI, 1.02-1.15]) and systolic blood pressure after adjusting for diastolic blood pressure (OR per 10-mm Hg increase, 1.23 [95% CI, 1.01-1.50]). Conclusions and Relevance:This genetic association study found novel genetic associations between high HDL cholesterol concentrations and high systolic blood pressure with higher risk of AD. These findings may inspire new drug targeting and improved prevention implementation.

AbstractBees are major pollinators of flowering plants and thus are important ecosystem service providers for natural habitats and crops. Evolution led to a wide range of adaptations in behaviors, morphology and ecological traits. Many plants rely on specialized bee species for pollination events, and so this interdependence can make them increasingly vulnerable to ongoing threats of habitat loss and pesticide exposure. Studying the genomes of bee species across different life histories and ecological specializations can help understand the evolution of these traits more generally, but also inform conservation efforts forCamptopoeum frieseispecifically.Here, we present the reference genome of the solitary beeCamptopoeum friesei(Arthropoda; Insecta; Hymenoptera; Andrenidae).C. frieseiis highly dependent on steppe habitats where it nests in saline soils. Further, it is highly specialized (oligolectic) on a few Asteraceae:CentaureaandCirsium, in particular onCentaurea stoebe. As a consequence of its high specialization level, it is of its ecological niche with an extremely scattered and rare habitat,C. frieseiis highly threatened in central Europe, albeit local aggregations can be rich in individuals.The high-quality genome assembly for the colourful beeCamptopoeum frieseiwas generated using long-read PacBio HiFi in combination with chromatin conformation capture (Hi-C) sequencing. The genome spans 367.7 megabases (Mb), N50 of 25.2 Mb. The majority of the assembly is scaffolded into 10 chromosomes and harbours ∼40% repeats.Species taxonomyEukaryota; Opisthokonta; Metazoa; Eumetazoa; Bilateria; Protostomia; Ecdysozoa; Panarthropoda; Arthropoda; Mandibulata; Pancrustacea; Hexapoda; Insecta; Dicondylia; Pterygota; Neoptera; Endopterygota; Hymenoptera; Apocrita; Aculeata; Apoidea; Anthophila; Andrenidae; Panurginae; Panurgini;Camptopoeum frieseiMocsáry, 1894 (NCBI:txid2918745)

Male-pattern hair loss (MPHL) is common and highly heritable. While genome-wide association studies (GWAS) have generated insights into the contribution of common variants to MPHL etiology, the relevance of rare variants remains unclear. To determine the contribution of rare variants to MPHL etiology, we perform gene-based and single-variant analyses in exome-sequencing data from 72,469 male UK Biobank participants. While our population-level risk prediction suggests that rare variants make only a minor contribution to general MPHL risk, our rare variant collapsing tests identified a total of five significant gene associations. These findings provide additional evidence for previously implicated genes (EDA2R, WNT10A) and highlight novel risk genes at and beyond GWAS loci (HEPH, CEPT1, EIF3F). Furthermore, MPHL-associated genes are enriched for genes considered causal for monogenic trichoses. Together, our findings broaden the MPHL-associated allelic spectrum and provide insights into MPHL pathobiology and a shared basis with monogenic hair loss disorders.