Corrigendum: Sex differences in the genetics of sarcoidosis across European and African ancestry populations.

[This corrects the article DOI: 10.3389/fmed.2023.

Multiple Correspondence Analysis and HLA-Associations of Organ Involvement in a Large Cohort of African-American and European-American Patients with Sarcoidosis.

Sarcoidosis is a systemic granulomatous disease with predominant pulmonary involvement and vast heterogeneity of clinical manifestations and disease outcomes. African American (AA) patients suffer greater morbidity and mortality. Using Multiple Correspondence Analysis, we identified seven clusters of organ involvement in European American (EA; n = 385) patients which were similar to those previously described in a Pan-European (GenPhenReSa) and a Spanish cohort (SARCOGEAS).

Sex differences in the genetics of sarcoidosis across European and African ancestry populations.

Background: Sex differences in the susceptibility of sarcoidosis are unknown. The study aims to identify sex-dependent genetic variations in two clinical sarcoidosis phenotypes: Löfgren's syndrome (LS) and non-Löfgren's syndrome (non-LS).

Methods: A meta-analysis of genome-wide association studies was conducted on Europeans and African Americans, totaling 10,103 individuals from three population-based cohorts, Sweden ( = 3,843), Germany ( = 3,342), and the United States ( = 2,918), followed by an SNP lookup in the UK Biobank (UKB, = 387,945).

Novel HLA associations with outcomes of Mycobacterium tuberculosis exposure and sarcoidosis in individuals of African ancestry using nearest-neighbor feature selection.

Tuberculosis and sarcoidosis are inflammatory diseases characterized by granulomas that may occur in any organ but are often found in the lung. The panoply of classical human leukocyte antigen (HLA) alleles associated with occurrence and/or severity of both diseases varies considerably across studies. This heterogeneity of results, due to variation in factors like ancestry and disease subphenotype, as well as the use of simple modeling strategies to elucidate likely complex relationships, has made conclusions about underlying commonalities difficult.

Genome-Wide Association Study of Ocular Sarcoidosis Confirms HLA Associations and Implicates Barrier Function and Autoimmunity in African Americans.

: Identify genes associated with ocular sarcoidosis (OS).: We genotyped 1.1 million genetic variants to identify significant OS associations, defined as those that achieved < 5 × 10 in a genome-wide comparison of OS cases to healthy controls in our European- or African-American cohorts (EA, AA).

Myocardial contractile patterns predict future cardiac events in sarcoidosis.

The poor prognosis of cardiac sarcoidosis (CS) underscores the need for risk stratification. We evaluated 84 consecutive sarcoidosis patients who were referred for echocardiographic studies for cardiac symptoms or abnormal electrocardiograms. In 54 patients without previous diagnosis of CS or other known structural heart disease, 13 reached endpoints during (median) 24 months follow up.

Isolated extraocular orbital mass: a rare presentation of sarcoidosis.

We report a case of orbital sarcoidosis in a 66 year old male who presented with one month history of right eye swelling and intermittent diplopia. MRI revealed an enhancing infiltrative soft tissue mass in the inferior aspect of the right orbit and biopsy of the mass demonstrated non-necrotizing granulomas. Chest CT scan was normal and PET scan showed no other organ involvement.

High-Density Genetic Mapping Identifies New Susceptibility Variants in Sarcoidosis Phenotypes and Shows Genomic-driven Phenotypic Differences.

Rationale: Sarcoidosis is a multisystem disease of unknown cause. Löfgren's syndrome (LS) is a characteristic subgroup of sarcoidosis that is associated with a good prognosis in sarcoidosis. However, little is known about its genetic architecture or its broader phenotype, non-LS sarcoidosis.

Fine mapping of chromosome 15q25 implicates ZNF592 in neurosarcoidosis patients.

Neurosarcoidosis is a clinical subtype of sarcoidosis characterized by the presence of granulomas in the nervous system. Here, we report a highly significant association with a variant (rs75652600, P = 3.12 × 10(-8), odds ratios = 4.

Novel pharmacotherapy of sarcoidosis.

Sarcoidosis is a multisystem granulomatous disease of unknown etiology that most commonly affects the lungs. Treatment of sarcoidosis can be challenging as it is often difficult to measure disease activity and distinguish active inflammation from fibrosis. Identifying the inflammatory mediators in sarcoidosis has led to the development and use of novel therapeutic agents.

Comparing Hospitalist-Resident to Hospitalist-Midlevel Practitioner Team Performance on Length of Stay and Direct Patient Care Cost.

Background: A perception exists that residents are more costly than midlevel providers (MLPs). Since graduate medical education (GME) funding is a key issue for teaching programs, hospitals should conduct cost-benefit analyses when considering staffing models.

Objective: Our aim was to compare direct patient care costs and length of stay (LOS) between resident and MLP inpatient teams.

Identification of Immune-Relevant Factors Conferring Sarcoidosis Genetic Risk.

Rationale: Genetic variation plays a significant role in the etiology of sarcoidosis. However, only a small fraction of its heritability has been explained so far.

Objectives: To define further genetic risk loci for sarcoidosis, we used the Immunochip for a candidate gene association study of immune-associated loci.

Association of HLA-DRB1 with Sarcoidosis Susceptibility and Progression in African Americans.

HLA-DRB1 is a sarcoidosis risk gene, and the *03:01 allele is strongly associated with disease resolution in European sarcoidosis cases. Whereas the HLA-DRB1 variation is associated with sarcoidosis susceptibility in African Americans, DRB1 risk alleles are not as well defined, and associations with disease resolution have not been studied. Associations between genotyped and imputed HLA-DRB1 alleles and disease susceptibility/resolution were evaluated in a sample of 1,277 African-American patients with sarcoidosis and 1,467 control subjects.

Performance of HLA allele prediction methods in African Americans for class II genes HLA-DRB1, -DQB1, and -DPB1.

Background: The expense of human leukocyte antigen (HLA) allele genotyping has motivated the development of imputation methods that use dense single nucleotide polymorphism (SNP) genotype data and the region's haplotype structure, but the performance of these methods in admixed populations (such as African Americans) has not been adequately evaluated. We compared genotype-based-derived from both genome-wide genotyping and targeted sequencing-imputation results to existing allele data for HLA-DRB1, -DQB1, and -DPB1.

Results: In European Americans, the newly-developed HLA Genotype Imputation with Attribute Bagging (HIBAG) method outperformed HLA*IMP:02.

Efficient generalized least squares method for mixed population and family-based samples in genome-wide association studies.

Genome-wide association studies (GWAS) that draw samples from multiple studies with a mixture of relationship structures are becoming more common. Analytical methods exist for using mixed-sample data, but few methods have been proposed for the analysis of genotype-by-environment (G×E) interactions. Using GWAS data from a study of sarcoidosis susceptibility genes in related and unrelated African Americans, we explored the current analytic options for genotype association testing in studies using both unrelated and family-based designs.

New brain lesions in a patient with sarcoidosis: is it neurosarcoidosis?

A 45-year-old woman with pulmonary sarcoidosis diagnosed 5 years previously, who was on treatment with prednisone and methotrexate for 1year, developed partial seizure with secondary generalization. MRI showed three non-cavitary enhancing lesions in the cerebello-occipital region. These lesions were presumed to be neurosarcoidosis.

The most common cause of hemoptysis worldwide: a fluke?

Global travel is associated with an increasing incidence of helminthic infections in nonendemic regions. We describe a patient with recurrent hemoptysis from a chronic infection not commonly found in the USA.

Admixture fine-mapping in African Americans implicates XAF1 as a possible sarcoidosis risk gene.

Sarcoidosis is a complex, multi-organ granulomatous disease with a likely genetic component. West African ancestry confers a higher risk for sarcoidosis than European ancestry. Admixture mapping provides the most direct method to locate genes that underlie such ethnic variation in disease risk.

A case of hut lung: scanning electron microscopy with energy dispersive x-ray spectroscopy analysis of a domestically acquired form of pneumoconiosis.

Hut lung is a pneumoconiosis caused by exposure to smoke derived from biomass fuels used for cooking in poorly ventilated huts. We report, to our knowledge, the first analysis of the dust deposited in the lungs in hut lung by scanning electron microscopy with energy dispersive x-ray spectroscopy (SEM/EDS). A Bhutanese woman presented with shortness of breath and an abnormal chest radiograph.

Extending admixture mapping to nuclear pedigrees: application to sarcoidosis.

We describe statistical methods that extend the application of admixture mapping from unrelated individuals to nuclear pedigrees, allowing existing pedigree-based collections to be fully exploited. Computational challenges have been overcome by developing a fast algorithm that exploits the factorial structure of the underlying model of ancestry transitions. This has been implemented as an extension of the program ADMIXMAP.

Genome-wide association study of African and European Americans implicates multiple shared and ethnic specific loci in sarcoidosis susceptibility.

Sarcoidosis is a systemic inflammatory disease characterized by the formation of granulomas in affected organs. Genome-wide association studies (GWASs) of this disease have been conducted only in European population. We present the first sarcoidosis GWAS in African Americans (AAs, 818 cases and 1,088 related controls) followed by replication in independent sets of AAs (455 cases and 557 controls) and European Americans (EAs, 442 cases and 2,284 controls).