Novel genes and sex differences in COVID-19 severity.

Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10-8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10-22 and P = 8.1 × 10-12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10-8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10-8) and ARHGAP33 (P = 1.3 × 10-8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10-8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.

Runs of homozygosity: windows into population history and trait architecture.

Long runs of homozygosity (ROH) arise when identical haplotypes are inherited from each parent and thus a long tract of genotypes is homozygous. Cousin marriage or inbreeding gives rise to such autozygosity; however, genome-wide data reveal that ROH are universally common in human genomes even among outbred individuals. The number and length of ROH reflect individual demographic history, while the homozygosity burden can be used to investigate the genetic architecture of complex disease. We discuss how to identify ROH in genome-wide microarray and sequence data, their distribution in human populations and their application to the understanding of inbreeding depression and disease risk.

Frequency, location, and diameter of the anastomosis between the posterior superior alveolar artery and the infraorbital artery in imaging studies: systematic review and meta-analysis.

The anastomosis between the posterior superior alveolar artery (PSAA) and the infraorbital artery (IOA) courses along half of the lateral wall of the maxillary sinus. Risk of injury to the anastomosis between PSAA and IOA during surgical procedures has been reported. The aim of the present study was to carry out a systematic review and meta-analysis to determine the frequency, location, and diameter of the anastomosis between PSAA and IOA in imaging studies (cone-beam computed tomography, spiral cone-beam computed tomography, and computed tomography). A search was carried out in the PubMed, EMBASE, and LILACS. Original works were included reporting imaging studies to analyze the frequency, location, and diameter of the anastomosis in humans. The risks of bias were analyzed using the AQUA tool. Generalized linear mixed models were used to estimate the frequency and the 95% CI in the meta-analysis. The variance in prevalence estimates was stabilized by logit transformation. The qualitative analysis included 49 studies with 10,837 patients. The frequency of the anastomosis between PSAA and IOA was 74% (prediction interval 0.20-0.97%). The anastomosis was most frequently located in the intraosseous region (60.0%), followed by the submembranous region (33.0%), and least frequently in an extraosseous location (5.0%). Arteries with diameter of 1.0-1.9 mm were most frequent (32.0%), followed by arteries with diameter less than 1 mm (23.0%); a small number with diameter greater than 2 mm was recorded (4.0%). These data can be used as a reference to help surgeons when planning interventions in the lateral wall of the maxillary sinus. Registration number: INPLASY, number 202120071.

Differences in the hepatitis C virus cascade of care and time to initiation of therapy among vulnerable subpopulations using a mobile unit as point-of-care.

BACKGROUND AND AIMS: People who inject drugs (PWID) and other marginalized populations with high hepatitis C virus (HCV) infection rates represent a unique challenge for treatment initiation due to health, administrative and social barriers. We analysed the HCV cascade of care (CoC) in some vulnerable subpopulations in Madrid, Spain, when using a mobile point-of-care (PoC). METHODS: From 2019 to 2021, a mobile unit was used to screen active HCV using a linkage-to-care and two-step PoC-based strategy. Viremic participants were grouped into four subgroups: PWID, homeless individuals and people with a mental health disorder (MHD) and alcohol use disorder (AUD). Logistic regression, and Cox and Aalen's additive models were used to analyse associated factors and differences between groups. RESULTS: A prospectively recruited cohort of 214 HCV-infected individuals (73 PWID, 141 homeless, 57 with a MHD and 91 with AUD) participated in the study. The overall HCV CoC analysis found that 178 (83.1%) attended a hospital, 164 (76.6%) initiated direct-acting antiviral therapy and 141 (65.8%) completed therapy, of which 99 (95.2%) achieved sustained virological response (SVR). PWID were significantly less likely to initiate treatment, whereas individuals with AUD waited longer before starting the treatment. Both people with AUD and PWID were significantly less likely to complete HCV treatment. CONCLUSIONS: Overall, SVR was achieved in the majority of the participants treated. However, PWID need better linkage to care and treatment, whereas PWID and AUD need more support for treatment completion.

Implication of mucus-secreting cells, acidophilic granulocytes and monocytes/macrophages in the resolution of skin inflammation caused by subcutaneous injection of λ/κ-carrageenin to gilthead seabream (Sparus aurata) specimens.

To date, the mechanisms of inflammation have been poorly studied in fish of commercial interest, due to the lack of development of appropriate experimental models. The current study evaluated a local inflammation triggered by a polymeric carrageenin mixture (a mucopolysaccharide derived from the red seaweed Chondrus crispus) in the skin of gilthead seabream (Sparus aurata). Fish were injected subcutaneously with phosphate-buffered saline (as control) or λ/κ-carrageenin (1%), and skin samples from the injection sites were collected 1.5, 3 and 6 hr post-injection, processed for inclusion in paraplast and stained with haematoxylin-eosin, Alcian blue or periodic acid-Schiff. Furthermore, immunohistochemistry and expression analyses of several cells' markers and proinflammatory genes were also analysed in samples of the injected sites. Microscopic results indicated an increased number of skin mucus-secreting cells and acidophilic granulocytes in the skin of fish studied at 1.5 hr and 3 hr post-injection with carrageenin, respectively, with respect to the data obtained in control fish. Otherwise, both the gene expression of the non-specific cytotoxic cell marker (granzyme B, grb) and the proinflammatory cytokine (interleukin-1ß, il-1ß) were up-regulated at 1.5 hr in the skin of fish injected with carrageenin compared with the control fish, whilst the gene expression of acidophilic granulocyte markers (NADPH oxidase subunit Phox22 and Phox40, phox22 and phox40) was up-regulated at 3 and 6 hr in the carrageenin group, compared with the control group. In addition, the gene expression of myeloperoxidase (mpo) was also up-regulated at 6 hr in the skin of fish injected with carrageenin in comparison with control samples. The present results indicate the chronological participation of two important immune cells involved in the resolution of the inflammation in the skin of gilthead seabream.

Ultrasonography study of the skin wound healing process in gilthead seabream (Sparus aurata).

This work aimed to carry out an in vivo study of the skin healing process in gilthead seabream (Sparus aurata) after being experimentally wounded. Firstly, the structure of normal skin was studied by real-time ultrasonography (Vevo Lab, VisualSonics) and light microscopy. Besides this, experimental wounds were made on the left flank of each fish with a circular biopsy punch (8 mm diameter) below the lateral line. The healing process was assessed on live fish at 0, 6, 11 and 23 days post-wounding using the real-time ultrasonography in B-mode and Power Doppler mode (Vevo 3100 FUJIFILM, VisualSonics). Through the ultrasonography images, both the skin structure and the evolution of the changes that wounds originated in the surrounding tissues were studied in vivo over time. Concomitantly, the pattern of neovascularization in the wounded area was followed during the healing process and it was demonstrated that, although the neovascularization started very early after the skin damage, it was increased in wounded areas from day 11 post-wounding onwards. The results obtained proved the utility and power of using ultrasounds in fish to evaluate in vivo complex biological processes in real time, which are difficult to study by other methodologies. The present data shed some light on the reparation of external injuries in aquatic vertebrates.

Effects of subcutaneous injection of λ/κ-carrageenin on the immune and liver antioxidant status of gilthead seabream (Sparus aurata).

This study investigated the acute inflammatory response induced by subcutaneous injection of carrageenin (1%) or phosphate-buffered saline (control) in gilthead seabream (Sparus aurata). Skin mucus, serum, head kidney (HK) and liver were sampled at 1.5, 3 and 6 hr post-injection (p.i.) to determine the immune and antioxidant status of this fish species. The skin mucus of the carrageenin group showed increased superoxide dismutase and peroxidase activities, lysozyme abundance, bactericidal activity against Vibrio anguillarum and Photobacterium damselae, and total immunoglobulins compared with those of the control group. However, the carrageenin-injected fish sampled at 6 hr p.i. showed decreased protease activity in the skin mucus and peroxidase activity in the HK leucocytes compared with the control. Moreover, the carrageenin injection had no effects on the systemic immune system, but it reduced the liver catalase activities at both 3 and 6 hr in the carrageenin group relative to those in the control group. The expression levels of several proinflammatory and cell marker genes in the HK and liver were also determined. In the HK, the expression levels of interleukin-1ß and prostaglandin D synthase 1 were upregulated at 1.5 and 3 hr, respectively, in the carrageenin group compared with those in the control group. Contrarily, the expression of the NADPH oxidase subunit phox40 (an acidophilic granulocyte marker) in the carrageenin group at 6 hr was downregulated compared with that in the control group. These results suggested that subcutaneous injection of κ/λ-carrageenin in gilthead seabream triggered an acute skin inflammation characterized by the rapid recruitment of acidophilic granulocytes and the release of humoral mediators into the skin mucus.

Oral ingestion versus endoscopic delivery of endoscopic capsule in patients with previous gastrointestinal surgery (ORENCES study): A Spanish multicentre observational study.

BACKGROUND: Small Bowel Capsule Endoscopy is the first-choice technique for investigating the majority of small bowel diseases. Its most common complications are related to incomplete examinations and capsule retention. There is no consensus on how patients with previous gastrointestinal surgery should receive the capsule. OBJECTIVE: The primary endpoint was to compare the rate of complete small-bowel examinations (completion rate) between oral ingestion and endoscopic delivery of the capsule. The secondary endpoint was to compare diagnostic yield and adverse events in the two groups. METHODS: A retrospective observational study was conducted in nine hospitals in Spain. Demographic data, previous surgery, indication for capsule endoscopy, intestinal transit time, diagnosis, completion rate (percentage of capsules reaching the caecum), diagnostic yield (percentage of results compatible with indication for the exam) and adverse events were collected. RESULTS: From January 2009 to May 2019 fifty-seven patients were included (39 male, mean age 66±15 years). The most common indications for the exam were "overt" (50.9%) and "occult" (35.1%) small bowel bleeding. Previous Billroth II gastrectomy and Roux-en-Y gastric bypass were present in 52.6% and 17.5% of patients respectively. The capsule was swallowed in 34 patients and placed endoscopically in 23 patients. No significant differences were observed between the oral ingestion and endoscopic delivery groups in terms of completion rate (82.4% vs. 78.3%; p=0.742), diagnostic yield (41.2% vs. 52.2%; p=0.432) or small bowel transit time (301 vs. 377min, p=0.118). No capsule retention occurred. Only one severe adverse event (anastomotic perforation) was observed in the endoscopic delivery group. CONCLUSIONS: In our case series, there were no significant differences between oral ingestion and endoscopic delivery in terms of completion rate, diagnostic yield or safety. Being less invasive, oral ingestion of the capsule should be the first-choice method in patients with previous gastrointestinal surgery.

Short-term impacts of COVID-19 on food security and nutrition in rural Guatemala: Phone-based farm household survey evidence.

This article examines the short-term effects of the COVID-19 lockdown on food security and nutrition in rural Guatemala. We rely on a comprehensive panel dataset of 1,824 small agricultural households collected over two survey rounds, on November-December 2019 and May-June 2020. We place special emphasis on changes in agricultural and nonagricultural income sources, including remittances, and changes in dietary diversity, including consumption of animal source foods (ASF) and fruits and vegetables (F&V). We find that COVID-19 affected the incomes, food security, and dietary patterns of households, with a decrease in ASF diversity and an increase in F&V diversity, and an overall net decrease in dietary diversity across all food groups. Dietary diversity among women in reproductive age, however, remained unchanged, and increased among children under 2 years old. Interestingly, households with relatively higher incomes appear to have reduced their dietary diversity to a larger extent than lower income ones, as well as households located in communities with more severe access restrictions. The focus of the study in a region with a high prevalence of poverty and chronic malnutrition provides an important perspective into the consequences of the lockdown in complex rural contexts with vulnerable populations and contributes to inform eventual recovery measures.

Crop prices, farm incomes, and food security during the COVID-19 pandemic in India: Phone-based producer survey evidence from Haryana State.

In March 2020, India declared a nationwide lockdown in response to the COVID-19 pandemic. Such restrictions on mobility interrupted the normal functioning of agricultural value chains. For a sample of 1767 tomato and wheat producers in the state of Haryana, we study to what extent the lockdown limited access to inputs, labor, machinery, and markets to produce, harvest, and sell their crops. We quantify crop income reductions during the first months of the lockdown and analyze to what extent these are associated with borrowing and food insecurity. We find that wheat producers, for whom state-led procurement guaranteed market access at fixed prices, suffered minimal declines in income. For tomato producers-an already more vulnerable population-income fell by 50% relative to their expected income in a normal year, largely due to a steep fall of tomato prices as they shifted from wholesale markets to local retail markets, resulting in a sharp increase in local supply. Relative to wheat producers affected by the lockdown, reduced income for tomato producers was associated with an increase in borrowing and reduced food security. We conclude that targeting producers of crops that face substantial price risk and introducing policies that stabilize market prices are important in efforts to aid recovery and build resilience of smallholder farmers.

Influence of skin wounds on the intestinal inflammatory response and barrier function: Protective role of dietary Shewanella putrefaciens SpPdp11 administration to gilthead seabream (Sparus aurata L.).

The effects of skin wounds on the intestinal barrier function and the beneficial effects of the dietary administration of Shewanella putrefaciens (known as SpPdp11) in gilthead seabream (Sparus aurata L.) were studied. Two replicates of fish were fed a commercial diet (control, CON) or CON diet enriched with 109 cfu g-1 SpPdp11 (SP diet) for 30 days. After this time, half of the fish were sampled, while the others were injured below the lateral line (wounded fish, W) and fed the same diets for an extra week before sampling (CON + W and SP + W groups). The intestinal histology and gene expression of different genes relevant for the intestinal barrier function were studied. The results showed that injured fish had a disordered enterocyte nucleus disposition, a more intense infiltration of mixed leucocytes and a thicker lamina propria in the intestine compared to the control fish. However, the fish in the SP + W group did not present these pathological symptoms in the intestine. No significant variations in the number of goblet cells were detected among the different experimental groups. Pro-inflammatory cytokines (colony-stimulating factor receptor 1, CSF1R, myeloperoxidase, MPO and interleukin-1ß, IL-1ß), mucins (intestinal mucin, IMUC and mucin 2, MUC2), and immunoglobulin T heavy chain (IGHT) were up-regulated, while tight junction protein occludin was down-regulated in the intestine from fish of the CON + W group. Similarly, the dietary administration of SpPdp11 markedly depressed the gene expression of pro-inflammatory cytokines, MUC2 and IGHT, but increased the gene expression of anti-inflammatory cytokine transforming growth factor-ß1 (TGF-ß1) and the tight junction proteins tricellulin and occluding after wounding. In brief, the skin wounds provoked an intestinal inflammatory response that included changes in the mucus layer and tight junction disruptions. Besides this, preventive administration of SpPdp11 alleviated the intestinal dysfunctions caused by skin wounds in gilthead seabream.

The alleviation of skin wound-induced intestinal barrier dysfunction via modulation of TLR signalling using arginine in gilthead seabream (Sparus aurata L).

The present study sought to investigate the effect of arginine on the involvement of toll-like receptors (TLRs) in skin wound-induced intestinal barrier dysfunction in gilthead seabream (Sparus aurata L.). Two replicates of fish (n = 8) were fed a commercial diet (CON, total 2.75% arginine), CON diet enriched with 1% arginine (ARG1, total 3.65% arginine) and 2% arginine (ARG2, total 4.53% arginine) for 30 days. Half of the fish were sampled, whereas the others were injured and sampled 7 days post-wounding. The intestinal histology results showed that a more intense infiltration of mixed leucocytes was evident in the wounded fish, which was remarkably reduced in fish that were fed the ARG1 diet. Serum IgM levels were significantly higher in the ARG1 group than levels in the CON group at 7 days post-wounding. Compared with the fish in the CON group after wounding, dietary administration of 1% arginine markedly downregulated the gene expression of TLRs (TLR2 and TLR5), MyD88, and proinflammatory cytokines (CSF1R, IL-1ß, and TNFα), but significantly enhanced the gene expression of IκBα, the anti-inflammatory cytokine TGF-ß1, and tight junction proteins (tricellulin and occludin) in wounded fish. Furthermore, the ARG2 diet demonstrated no additional benefits on intestinal cells, compared to both the ARG1 and the CON diets, and it even appeared to induce negative effects. In summary, dietary administration of 1% arginine significantly inhibited intestinal inflammatory response and tight junction disruption in skin-wounded gilthead seabream by modulating TLR signalling in the intestine.

Skin wound healing in gilthead seabream (Sparus aurata L.) fed diets supplemented with arginine.

Dietary administration of arginine on the wound healing process of gilthead seabream was studied. Two replicates of fish (n = 8) were fed with either a commercial diet [control diet (CON), no arginine added] and the CON diet supplemented with 1% arginine (ARG1) or with 2% arginine (ARG2) for 30 days. Afterward, half of the fish were sampled while the other half were injured and continued to be fed the same diet for an extra week. Results by image analysis showed that the wound closure rate was significantly improved in fish that were fed the ARG1 diet, compared with those in the CON group. After seven days of wound healing, the aminotransferase and creatine kinase levels in the serum and the protease and peroxidase activities in the skin mucus were down-regulated, while the immunoglobulin M level in the skin mucus was up-regulated in the ARG1 group after wounding and in the CON group before wounding. Compared with the CON diet, the ARG1 diet remarkedly depressed the gene expression of mpo, il-8, and tnf-α, and enhanced the gene expression of tgf-ß1, igf-1, pcna, krt2, mmp9, fn1α, and colIα and the antioxidant enzyme cat in the skin tissues after wounding. Furthermore, compared with both the ARG1 and the CON groups, negative effects of the ARG2 diet on wound healing were demonstrated. In conclusion, a 1% arginine supplementation facilitates skin wound healing and prevents a systemic inflammation reaction by alleviating the inflammatory response and enhancing the re-epithelialization and ECM biosynthesis in skin wound sites.

Radiological characterization of gilthead seabream (Sparus aurata) by X-ray computed tomography.

In recent years, the increasing use of fish as new animal models in scientific research and the growth of fish farming (mainly for human consumption) have highlighted the need for advanced technology to deepen our knowledge of fish biology. Hence, the present study was carried out to radiologically analyse the whole body of gilthead seabream (Sparus aurata) specimens using X-ray computed tomography (CT). Images were acquired in an Albira SPECT/PET/CT tri-modal preclinical-scanner. Segmentation, measurements and three-dimensional reconstruction were made using the Carestream Molecular imaging Albira CT system in conjunction with Pmod, AMIDE and Amira software packages. The results showed that the density values of gilthead seabream are in the range -700 to +2500 HU for the whole body. We also determined the density ranges that topographically coincide with the swim bladder, soft tissues, fat, skin and skeleton. This work describes, validates and demonstrates the application of a fully automated image analysis technique to study and quantify fish body composition, whether segmented or as a whole. In addition, the basis for applying this image technique in other in vivo studies is established.

Dietary supplementation of drumstick tree, Moringa oleifera, improves mucosal immune response in skin and gills of seabream, Sparus aurata, and attenuates the effect of hydrogen peroxide exposure.

In aquatic animals, the mucosal barrier is the first line of innate immune defence against external chemicals and pathogens. In this study, the effects of dietary Moringa oleifera leaf (MOL) supplementation on skin and gill mucosal immunity, antioxidants and stress responses were evaluated in seabream (Sparus aurata) fingerlings exposed to hydrogen peroxide (H2O2). A total of 144 specimens (10.11 ± 0.41 g) were divided into four treatments (three replicates per treatment contained 12 specimens each) and fed a non-supplemented control diet or a 1, 2.5 or 5% MOL-supplemented diet. After three weeks of feeding, six specimens from each aquarium were sampled for blood, mucus and tissues. The other six fish in each aquarium were subjected to H2O2 exposure. The results revealed that MOL did not negatively affect either cortisol or glucose levels. MOL supplementation significantly (P < 0.05) improved skin mucosal immunity-related characteristics, including phosphatase, peroxidase and lysozyme activity and IgM levels. Additionally, MOL upregulated the expression of antioxidant genes (sod and cat), an anti-inflammatory gene (tgf-ß), tight junction protein genes (occludin and zo-1), c3, and igm in both the skin and gills. However, H2O2 exposure significantly (P < 0.05) increased both cortisol and glucose levels and disrupted skin mucosal immune function by significantly (P < 0.05) decreasing phosphatase, peroxidase, protease, antiprotease and lysozyme activity and IgM levels. H2O2 exposure severely decreased the mRNA levels of the studied genes. MOL dietary supplementation at the 5% level successfully attenuated the negative effects of H2O2 on the mucosal immune response in both the skin and gills. In conclusion, dietary MOL supplementation at the 5% level is recommended to improve S. aurata mucosal immune function under both normal and stress conditions. Additionally, exposure to H2O2 disrupts the mucosal immunity of fish. This contributes knowledge on the routes involved in mucosal innate immunity and could help to understand the fish resistance against chemicals exposure. Graphical abstract.

Small bowel enteroscopy - A joint clinical guideline by the Spanish and Portuguese small-bowel study groups.

The present evidence-based guidelines are focused on the use of device-assisted enteroscopy in the management of small-bowel diseases. A panel of experts selected by the Spanish and Portuguese small-bowel study groups reviewed the available evidence focusing on the main indications of this technique, its role in the management algorithm of each indication, and its diagnostic and therapeutic yield. A set of recommendations was issued accordingly.

Runs of homozygosity in sub-Saharan African populations provide insights into complex demographic histories.

The study of runs of homozygosity (ROH) can shed light on population demographic history and cultural practices. We present a fine-scale ROH analysis of 1679 individuals from 28 sub-Saharan African (SSA) populations along with 1384 individuals from 17 worldwide populations. Using high-density SNP coverage, we could accurately identify ROH > 300 kb using PLINK software. The genomic distribution of ROH was analysed through the identification of ROH islands and regions of heterozygosity (RHZ). The analyses showed a heterogeneous distribution of autozygosity across SSA, revealing complex demographic histories. They highlight differences between African groups and can differentiate the impact of consanguineous practices (e.g. among the Somali) from endogamy (e.g. among several Khoe and San groups). Homozygosity cold and hotspots were shown to harbour multiple protein coding genes. Studying ROH therefore not only sheds light on population history, but can also be used to study genetic variation related to adaptation and potentially to the health of extant populations.

Correction to: Runs of homozygosity in sub-Saharan African populations provide insights into complex demographic histories.

In the Original article published, the figure number 5: Genomic distribution of ROH is incorrectly published. The correct figure is given below.

Inbreeding in the last ruling dynasty of Portugal: The house of Braganza.

OBJECTIVES: To determine whether: (1) there are high levels of inbreeding in a European royal dynasty that continues until the 20th century, and (2) whether inbreeding is negatively associated with pre-reproductive survival and longevity. METHODS: Genealogical information of all Braganza monarchs (1640-1910) was used to compute the individual's inbreeding coefficient (F) and the coefficient of kinship (θ) of the marriage which were examined in relation to two life-history traits. RESULTS: Mean F of the monarchs was 0.0530, close to that corresponding to the progeny of first cousins (F = 0.0625). A statistically significant effect of maternal inbreeding on offspring longevity (P = 0.037) and a significant effect of individual's F on survival from birth to 10 years (P = 0.023) were detected. CONCLUSIONS: Another European royal dynasty besides the Habsburgs had high levels of inbreeding, especially high during a period after the early modern age. The lineage showed evidence of inbreeding depression. Results support the hypothesis that an increase in maternal homozygosity affects the lifespan of the progeny.

Is the "Habsburg jaw" related to inbreeding?

Background: The "Habsburg jaw" has long been associated with inbreeding due to the high prevalence of consanguineous marriages in the Habsburg dynasty. However, it is thought that mandibular prognathism (MP) is under the influence of a dominant major gene.Aim: To investigate the relationship between the "Habsburg jaw" and the pedigree-based inbreeding coefficient (F) as a relative measure of genome homozygosity.Subjects and methods: The degree of MP and maxillary deficiency (MD) of 15 members of the Habsburg dynasty was quantified through the clinical analysis of 18 dysmorphic features diagnosed from 66 portraits.Results: A statistically significant correlation (r = 0.711, p = 0.003) between MP and MD was observed among individuals. Only MP showed a statistically significant positive regression on F as evidenced from univariate analysis (b = 6.36 ± 3.34, p = 0.040) and multivariate analysis (PCA) performed from single dysmorphic features (b = 14.10 ± 6.62, p = 0.027, for the first PC).Conclusion: Both MP and MD are generally involved in the "Habsburg jaw." The results showed a greater sensitivity to inbreeding for the lower third of the face and suggest a positive association between the "Habsburg jaw" and homozygosity and therefore a basically recessive inheritance pattern.