Biomedical subjects

Christian Erikstrup

Publications and source records attributed to Christian Erikstrup.

8 recordsLinked to original sources

PubMed2026

Plasma donation rates and infection risk: A multicentre observational study in Denmark.

BACKGROUND AND OBJECTIVES: The demand for plasma-derived medicinal products underscores the need to assess health effects of plasma donation. This study examines the association between plasma donation rates and infection risk in a country with voluntary, non-remunerated donation. MATERIALS AND METHODS: From 2016 to 2024, 45,615 first-time plasma donors were enrolled in a cohort study with time-varying exposure. Follow-up began 90 days after the first plasma donation, with donation rates recalculated every 90 days. Donation rates were categorized as 0, 1 (reference), 2-3, 4-5 or 6-8 donations. Infection was defined using Danish health registers. Survival models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: The median plasma donation rate was 2 (Q1, 1; Q3, 4). During follow-up, 15,498 donors experienced an infection. A trend of decreasing HRs for infection was observed with higher donation rates compared with a single donation (0 donations: HR: 0.89, 95% CI: 0.86-0.93; 2-3 donations: HR: 0.85, 95% CI: 0.81-0.89; 4-5 donations: HR: 0.65, 95% CI: 0.59-0.72; and 6-8 donations: HR: 0.48, 95% CI: 0.36-0.62). Findings were consistent across multiple regression models. CONCLUSION: In this study, higher plasma donation rates were associated with lower infection risk. Importantly, this inverse association is likely due to bias inherent to observational designs, particularly the internal healthy donor effect, which limits interpretation. Thus, no causal relationship between plasma donation rates and infection risk can be inferred. This underscores the challenges of assessing plasma donation safety using non-randomized data.

Adult↗

PubMed2026

Genomic analyses implicate hormonal and metabolic dysregulation in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) and its underlying features remain poorly understood. In this genetic study (n = 544,513), we expand the number of genetic loci from 16 to 29, and additionally identify 31 associated plasma proteins. Many risk-increasing loci were associated with later age at menopause, underscoring the reproductive longevity related to an increased oocyte number and/or availability across the lifespan. Hormonal regulation in the etiology of this condition, through metabolic and reproductive features, was emphasized. The proteomic analysis highlighted metabolic biology known to be related to PCOS. A polygenic risk score (PRS) was associated with adverse cardiometabolic outcomes, with differing relevance of testosterone and body mass index in women and men. Finally, while oligo-anovulation and anovulatory infertility are features of PCOS, we observed no impact of PCOS susceptibility on childlessness. We suggest that PCOS susceptibility confers balanced pleiotropic influences on fertility in women, and life-long adverse metabolic consequences in both sexes.

Humans↗

PubMed2026

Hidradenitis Suppurativa and Smoking, Obesity, Psoriasis, Inflammatory Bowel Disease, and Systemic Sclerosis: Results From A 2-Sample Mendelian Randomization Study.

IMPORTANCE: Smoking and obesity are associated with risk of hidradenitis suppurativa, and both are considered important environmental risk factors. However, a causal relationship remains unproven. OBJECTIVE: To primarily investigate the relationship between body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) and smoking and HS, and secondarily to investigate potential relationships between 3 inflammatory diseases (psoriasis, inflammatory bowel disease [IBD], and systemic sclerosis [SSc]) and HS. DESIGN, SETTING, AND PARTICIPANTS: A mendelian randomization (MR) study conducted in 2024 on 5 exposure phenotypes (BMI, smoking, psoriasis, IBD, and SSc) on the outcome of phenotype HS was conducted. The MR analyses used large genetic White European cohorts from genome-wide association studies (GWAS) of each of the 6 phenotypes. Initial analyses were conducted May, 2024, and were updated in May, 2025. EXPOSURE: The 5 exposure phenotypes using predetermined genome-wide significant single-nucleotide variants as proxies for each particular exposure. RESULTS: The GWAS on HS included 4814 case patients and more than 1.2 million controls from Denmark, Iceland, Finland, the UK, and the US. The BMI GWAS involved 700 000 individuals from the UK Biobank and GIANT consortium. Smoking data were obtained from 1.23 million participants in an international consortium. The psoriasis GWAS analyzed 39 498 case patients and 286 769 controls from White European populations and a DNA genetic testing company. The IBD GWAS meta-analysis included 38 155 case patients and 48 485 controls from the International Inflammatory Bowel Disease (IBD) Genetics Consortium. The SSc GWAS included 9095 case patients and 17 584 controls from White European populations. Genetic correlations (rg) were found between HS and all exposure phenotypes except SSc (BMI: rg = 0.36, P < .001; smoking: rg = 0.33, P < .001; IBD: rg = 0.25, P < .001; psoriasis: rg = 0.34, P < .001; SSc: rg = 0.33, P = .22). MR analyses supported an effect of BMI on HS (β = 0.87; odds ratio [OR] per BMI unit, 1.20; 95% CI, 1.17-1.23; P < .001) without signs of pleiotropy (slope: β = 0.91, P < .001, P for intercept = .76). Smoking showed a significant causal estimate (β = 0.59, P < .001), but results became inconclusive in subsequent sensitivity analyses. Among IBD, psoriasis, and SSc, results supported a causal effect of IBD on HS (β = 0.18, OR = 1.20; 95% CI, 1.15-1.24; P < .001), without signs of pleiotropy. CONCLUSIONS AND RELEVANCE: These findings indicate causal effects of IBD and increased BMI on the risk of HS. This information may help physicians inform patients about disease risk contributed by modifiable lifestyle behaviors, which can be beneficial for planning lifestyle interventions.

Humans↗

PubMed2025

The genetic architecture of fibromyalgia across 2.5 million individuals.

Fibromyalgia is a common and debilitating chronic pain syndrome of poorly understood etiology. Here, we conduct a multi-ancestry genome-wide association study meta-analysis across 2,563,755 individuals (54,629 cases and 2,509,126 controls) from 11 cohorts, identifying the first 26 risk loci for fibromyalgia. The strongest association was with a coding variant in HTT, the causal gene for Huntington's disease. Gene prioritization implicated the HTT regulator GPR52, as well as diverse genes with neural roles, including CAMKV, DCC, DRD2/NCAM1, MDGA2, and CELF4. Fibromyalgia heritability was exclusively enriched within brain tissues and neural cell types. Fibromyalgia showed strong, positive genetic correlation with a wide range of chronic pain, psychiatric, and somatic disorders, including genetic correlations above 0.7 with low back pain, post-traumatic stress disorder and irritable bowel syndrome. Despite large sex differences in fibromyalgia prevalence, the genetic architecture of fibromyalgia was nearly identical between males and females. This work provides the first robust genetic evidence defining fibromyalgia as a central nervous system disorder, thereby establishing a biological framework for its complex pathophysiology and extensive clinical comorbidities.

Journal Article↗

PubMed2025

Germline Variants Influence Chronic Liver Disease Progression through Distinct Pathways.

Cirrhosis and hepatocellular carcinoma (HCC) are long-term complications of chronic liver disease (CLD). In this large multi-ancestry genome-wide association study of all-cause cirrhosis (35,481 cases, 2.36M controls) and HCC (6,680 cases, 1.76M controls), we identified 27 loci associated with cirrhosis (10 novel) and 11 with HCC (three novel). Three novel cirrhosis loci were replicated in independent cohorts (e.g. FGF21, RPTOR, and IFNL3/4). Fifteen cirrhosis loci exhibited differential effects on cirrhosis risk via underlying etiologies, and six HCC loci influenced HCC risk indirectly via cirrhosis. In a gene-burden analysis of rare variants from whole-genome sequencing data in the VA Million Veteran Program (n=102,677), we identified GSTA5 as a novel cirrhosis-associated gene, while APOB and ATP9B were associated with and replicated for HCC. A high genetic risk score for cirrhosis was associated with a nearly doubled risk of CLD progressing to cirrhosis (HR=1.94, P=2×10-68) and of cirrhosis progressing to HCC (HR=1.65, P=7×10-08). Finally, among individuals with chronic hepatitis C who underwent antiviral therapy, cirrhosis risk was modified by variants in PNPLA3, IFNL3/4, and CD81 following pegylated interferon-α therapy, and by APOE lead variant following direct-acting antiviral therapy. These findings provide new insights into the complex genetic architecture of CLD progression with potential clinical and therapeutic implications.

Journal Article↗

PubMed2025

Genome-wide association study of long COVID.

Infections can lead to persistent symptoms and diseases such as shingles after varicella zoster or rheumatic fever after streptococcal infections. Similarly, severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection can result in long coronavirus disease (COVID), typically manifesting as fatigue, pulmonary symptoms and cognitive dysfunction. The biological mechanisms behind long COVID remain unclear. We performed a genome-wide association study for long COVID including up to 6,450 long COVID cases and 1,093,995 population controls from 24 studies across 16 countries. We discovered an association of FOXP4 with long COVID, independent of its previously identified association with severe COVID-19. The signal was replicated in 9,500 long COVID cases and 798,835 population controls. Given the transcription factor FOXP4's role in lung physiology and pathology, our findings highlight the importance of lung function in the pathophysiology of long COVID.

Humans↗

PubMed2025

Genome-wide association study meta-analysis provides insights into the etiology of heart failure and its subtypes.

Heart failure (HF) is a major contributor to global morbidity and mortality. While distinct clinical subtypes, defined by etiology and left ventricular ejection fraction, are well recognized, their genetic determinants remain inadequately understood. In this study, we report a genome-wide association study of HF and its subtypes in a sample of 1.9 million individuals. A total of 153,174 individuals had HF, of whom 44,012 had a nonischemic etiology (ni-HF). A subset of patients with ni-HF were stratified based on left ventricular systolic function, where data were available, identifying 5,406 individuals with reduced ejection fraction and 3,841 with preserved ejection fraction. We identify 66 genetic loci associated with HF and its subtypes, 37 of which have not previously been reported. Using functionally informed gene prioritization methods, we predict effector genes for each identified locus, and map these to etiologic disease clusters through phenome-wide association analysis, network analysis and colocalization. Through heritability enrichment analysis, we highlight the role of extracardiac tissues in disease etiology. We then examine the differential associations of upstream risk factors with HF subtypes using Mendelian randomization. These findings extend our understanding of the mechanisms underlying HF etiology and may inform future approaches to prevention and treatment.

Humans↗

PubMed2024

Genome-Wide Association Study of Accessory Atrioventricular Pathways.

IMPORTANCE: Understanding of the genetics of accessory atrioventricular pathways (APs) and affiliated arrhythmias is limited. OBJECTIVE: To investigate the genetics of APs and affiliated arrhythmias. DESIGN, SETTING, AND PARTICIPANTS: This was a genome-wide association study (GWAS) of APs, defined by International Classification of Diseases (ICD) codes and/or confirmed by electrophysiology (EP) study. Genome-wide significant AP variants were tested for association with AP-affiliated arrhythmias: paroxysmal supraventricular tachycardia (PSVT), atrial fibrillation (AF), ventricular tachycardia, and cardiac arrest. AP variants were also tested in data on other heart diseases and measures of cardiac physiology. Individuals with APs and control individuals from Iceland (deCODE Genetics), Denmark (Copenhagen Hospital Biobank, Danish Blood Donor Study, and SupraGen/the Danish General Suburban Population Study [GESUS]), the US (Intermountain Healthcare), and the United Kingdom (UK Biobank) were included. Time of phenotype data collection ranged from January 1983 to December 2022. Data were analyzed from August 2022 to January 2024. EXPOSURES: Sequence variants. MAIN OUTCOMES AND MEASURES: Genome-wide significant association of sequence variants with APs. RESULTS: The GWAS included 2310 individuals with APs (median [IQR] age, 43 [28-57] years; 1252 [54.2%] male and 1058 [45.8%] female) and 1 206 977 control individuals (median [IQR] year of birth, 1955 [1945-1970]; 632 888 [52.4%] female and 574 089 [47.6%] male). Of the individuals with APs, 909 had been confirmed in EP study. Three common missense variants were associated with APs, in the genes CCDC141 (p.Arg935Trp: adjusted odds ratio [aOR], 1.37; 95% CI, 1.24-1.52, and p.Ala141Val: aOR, 1.55; 95% CI 1.34-1.80) and SCN10A (p.Ala1073Val: OR, 1.22; 95% CI, 1.15-1.30). The 3 variants associated with PSVT and the SCN10A variant associated with AF, supporting an effect on AP-affiliated arrhythmias. All 3 AP risk alleles were associated with higher heart rate and shorter PR interval, and have reported associations with chronotropic response. CONCLUSIONS AND RELEVANCE: Associations were found between sequence variants and APs that were also associated with risk of PSVT, and thus likely atrioventricular reentrant tachycardia, but had allele-specific associations with AF and conduction disorders. Genetic variation in the modulation of heart rate, chronotropic response, and atrial or atrioventricular node conduction velocity may play a role in the risk of AP-affiliated arrhythmias. Further research into CCDC141 could provide insights for antiarrhythmic therapeutic targeting in the presence of an AP.

Humans↗