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The supracondylar process is a nonpathological projection from the distal humerus that in some patients, can result in compression of regional neurovascular structures, for example, median nerve. Since the first description of the supracondylar process in 1818, it has also been a focus of anthropological study because of its possible relevance to human origins and relationships to other species. Although its overall incidence is low, it is more common in races of European descent. It is particularly interesting for anatomists and anthropologists, but knowledge of its anatomical relationships and effect on pathological processes helps in the diagnosis and treatment of supracondylar process syndrome. One of the most detailed descriptions of this variant process stems from the work of Buntaro Adachi. Herein, a translation of his findings is provided and a review of the supracondylar process and its potential pathological presentations presented.

BACKGROUND The prevalence of myopia is increasing globally including in Europe and parts of Asia but Australian data are lacking. This study aim described the change in myopia prevalence in middle-aged Australian adults over approximately a 20-year period. METHODS Two contemporary Western Australian studies (conducted in mid-late 2010s): the coastal-regional Busselton Healthy Ageing Study (BHAS) and the urban Gen1 of the Raine Study (G1RS) were compared to two earlier studies (early-mid 1990s) in Australia: the urban Blue Mountains Eye Study (BMES) and urban/regional Melbourne Visual Impairment Project (MVIP). Refractive error was measured by autorefraction, vertometry, or subjective refraction. Participants (49-70 years) of European descent without self-reported/diagnosed cataract, corneal disease, or refractive or corneal surgery were included. RESULTS After exclusions, data were available from 2217, 1760, 700, 2987 and 756 participants from BMES, urban MVIP, regional MVIP, BHAS, and G1RS, respectively. The mean age ranged from 57.1 ± 4.6 years in the G1RS to 60.1 ± 6.0 years in the BMES; 44-48% of participants were male. When stratified by location, the contemporary urban G1RS cohort had a higher age-standardised myopia prevalence than the urban MVIP and BMES cohorts (29.2%, 16.4%, and 23.9%, p

While the student population in higher education has become more ethnically diverse the professoriate in universities remain predominantly of European descent. Reflecting this disparity of represen...

To investigate cross-ancestry genetics of complex traits, we conducted a phenome-wide analysis of loci with heterogeneous effects across African, Admixed-American, Central/South Asian, East Asian, European and Middle Eastern participants of the UK Biobank (N = 441 331). Testing 843 phenotypes, we identified 82 independent genomic regions mapping variants showing genome-wide significant (GWS) associations (P

In the present study a software tool for craniometric ancestry estimation, AncesTrees, was evaluated in an identified Brazilian skeletal sample with known self-reported ancestry. Twenty-three craniometric measures were obtained from each skull and analyzed using AncesTrees software, with two classification strategies—tournamentForest and ancestralForest algorithm. The tournamentForest (53.54%) and ancestralForest algorithms with three ancestry groups (50.96%) were more accurate to classify Europeans, while the ancestralForest algorithm with six (50.00%) and two (67.64%) groups were more accurate to estimate the ancestry of African descents. Admixed ancestry specimens were classified predominantly as European descent. The use of the ancestralForest algorithm considering only European and African origin (58.42%) was the most accurate setup for ancestry estimation in Brazilian skulls. Supervised classification algorithms and tools such as the AncesTrees work based on data analysis and pattern matching, and there is no Brazilian sample in its database, the software showed a low accuracy Brazilian samples. The incorporation of representative craniometric data obtained from Brazilian skulls into the software database may significantly increase the accuracy of ancestry estimates.

Previous genetic studies on hair morphology focused on the overall morphology of the hair using data collected by self-report or researcher observation. Here, we present the first genome-wide association study (GWAS) of a micro-level quantitative measure of hair curvature. We compare these results to GWAS results obtained using a macro-level classification of observable hair curvature performed in the same sample of twins and siblings of European descent. Observational data were collected by trained observers, while quantitative data were acquired using an Optical Fibre Diameter Analyser (OFDA). The GWAS for both the observational and quantitative measures of hair curvature resulted in genome-wide significant signals at chromosome 1q21.3 close to the trichohyalin (TCHH) gene, previously shown to harbor variants associated with straight hair morphology in Europeans. All genetic variants reaching genome-wide significance for both GWAS (quantitative measure lead single-nucleotide polymorphism [SNP] rs12130862, p = 9.5 × 10–09; observational measure lead SNP rs11803731, p = 2.1 × 10–17) were in moderate to very high linkage disequilibrium (LD) with each other (minimum r2 = .45), indicating they represent the same genetic locus. Conditional analyses confirmed the presence of only one signal associated with each measure at this locus. Results from the quantitative measures reconfirmed the accuracy of observational measures.

Unfortunately, many patients referred for hematopoietic cell transplant will not have a fully matched related donor, and finding matched unrelated donors through the registry may be difficult, especially if the recipient is not of Northern European descent [N Engl J Med 2014;371:339‐348]. Umbilical cord blood (UCB) has been an available graft source for hematopoietic cell transplant for more than 30 years, since the first UCB transplant was performed in the late 1980s [N Engl J Med 1989;321:1174‐1178]. UCB is readily available, has low immunogenicity, and does not require as strict of human leukocyte antigen (HLA) matching compared to other graft sources [N Engl J Med 2004;351:2265‐2275]. According to data from the Center for International Blood and Marrow Transplant Research (CIBMTR), an estimated 500 patients in the US will have received a UCB transplant in 2018. Since 2014, haploidentical transplants have surpassed UCB transplants performed in the United States (CIBMTR Summary Slides, 2018, available at https://www.cibmtr.org). Increased use of haploidentical transplants has brought to light concerns about UCB transplants, including delayed engraftment and graft failure, increased nonrelapse mortality, increased infection risk, and UCB acquisition costs [Lancet Oncol 2010;11:653‐660; Biol Blood Marrow Transplant 2019;1456‐1464]. These concerns will need to be addressed for UCB to remain a viable option as a graft source for hematopoietic cell transplant. Other promising therapeutic benefits for UCB, in addition to hematopoietic cell transplant, is its use in regenerative medicine and immune modulation, which is currently being evaluated in ongoing clinical trials., Alternative donors, haploidentical donors and umbilical cord blood (UCB), are viable graft options for hematopoietic transplant if a patient does not have a matched related or unrelated donor. UCB is rapidly available, has low immunogenicity, and a potentially lower incidence of chronic graft vs host disease compared to other graft sources. However, UCB has several disadvantages that may impact the success of a hematopoietic transplant including delayed engraftment, graft failure, increased infection, and increased transplant‐related mortality. Ongoing studies in ex vivo expansion, homing, and combined grafts are evaluating ways to reduce or eliminate the disadvantages associated with UCB grafts and improve hematopoietic transplant outcomes.

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, with few known risk factors and biomarkers. Several blood protein biomarkers have been linked to PDAC in previous studies, but these studies have assessed only a limited number of biomarkers, usually in small samples. In this study, we evaluated associations of circulating protein levels and PDAC risk using genetic instruments. Methods: To identify novel circulating protein biomarkers of PDAC, we studied 8,280 cases and 6,728 controls of European descent from the Pancreatic Cancer Cohort Consortium and the Pancreatic Cancer Case-Control Consortium, using genetic instruments of protein quantitative trait loci. Results: We observed associations between predicted concentrations of 38 proteins and PDAC risk at an FDR of < 0.05, including 23 of those proteins that showed an association even after Bonferroni correction. These include the protein encoded by ABO, which has been implicated as a potential target gene of PDAC risk variant. Eight of the identified proteins (LMA2L, TM11D, IP-10, ADH1B, STOM, TENC1, DOCK9, and CRBB2) were associated with PDAC risk after adjusting for previously reported PDAC risk variants (OR ranged from 0.79 to 1.52). Pathway enrichment analysis showed that the encoding genes for implicated proteins were significantly enriched in cancer-related pathways, such as STAT3 and IL15 production. Conclusions: We identified 38 candidates of protein biomarkers for PDAC risk. Impact: This study identifies novel protein biomarker candidates for PDAC, which if validated by additional studies, may contribute to the etiologic understanding of PDAC development.

When Gee described coeliac disease in 1888 and Dicke introduced the gluten-free diet in 1950, neither could have known the implications of what they had launched. Coeliac disease has moved from being an uncommon illness confined to children of European descent to one of the most common chronic disorders encountered in the western world that can occur at any age and in many other countries. Gluten-related disorders now include not only coeliac disease and dermatitis herpetiformis but also non-coeliac gluten sensitivity, wheat allergy and gluten ataxia (neuropathy). This chapter traces the early recognition of gluten-related disorders to the present time, highlighting some of the more important developments.

The purpose of estimating each part of the biological profile is to reduce the number of missing persons for comparison with unknown human remains. To serve this purpose each part must: 1) derive from information garnered from the remains, and 2) provide information that missing person’s community will generally agree describes them. Observer and statistical error, sampling error, and the disconnect between biological and social categories are all associated with each step of estimation, and can render aspects of the biological profile useless, or even harmful, to the ultimate goal of identification. Here, we examine patterns of phenetic variation within a group usually treated as homogeneous, European-descended populations in the United States and Australia, usually described as “White” (n = 365). We analyzed dental morphological data for biological distances and using several classification techniques. We find that structure exists among these groups. Accuracy of classification of individuals from contemporary Tennessee approaches forensic significance, compared to samples from New York, Ohio, and Australia. These results point out that researchers commonly seek structured variation among some populations but not others. We examine this point, and make recommendations to the field to change our approach to the estimation of population affinity so that it reflects the biological variation associated with social meaning relevant in local communities. Additionally, our approach to population affinity should be iterative, reflecting cultural changes over time, and reflexive, aware and responding to our own biases.

Context A recent study identified 14 low-frequency coding variants associated with body mass index (BMI) in 718 734 individuals predominantly of European ancestry. Objective We investigated the association of 2 genetic scores (GS) with i) the risk of severe/morbid obesity, ii) BMI variation before weight-loss intervention, iii) BMI change in response to an 18-month lifestyle/behavioral intervention program, and iv) BMI change up to 24 months after bariatric surgery. Methods The 14 low-frequency coding variants were genotyped or sequenced in 342 French adults with severe/morbid obesity and 574 French adult controls from the general population. We built risk and protective GS based on 6 BMI-increasing and 5 BMI-decreasing low-frequency coding variants that were polymorphic in our study. Results While the risk GS was not associated with severe/morbid obesity status, BMI-decreasing low-frequency coding variants were significantly less frequent in patients with severe/morbid obesity than in French adults from the general population. Neither the risk nor the protective GS was associated with BMI before intervention in patients with severe/morbid obesity, nor did they affect BMI change in response to a lifestyle/behavioral modification program. The protective GS was associated with a greater BMI decrease following bariatric surgery. The risk and protective GS were associated with a higher and lower risk of BMI regain after bariatric surgery. Conclusion Our data indicate that in populations of European descent, low-frequency coding variants associated with BMI in the general population also affect the outcomes of bariatric surgery in patients with severe/morbid obesity.

Schizophrenia is a common, chronic and debilitating neuropsychiatric syndrome affecting tens of millions of individuals worldwide. While rare genetic variants play a role in the etiology of schizophrenia, most of the currently explained liability is within common variation, suggesting that variation predating the human diaspora out of Africa harbors a large fraction of the common variant attributable heritability. However, common variant association studies in schizophrenia have concentrated mainly on cohorts of European descent. We describe genome-wide association studies of 6152 cases and 3918 controls of admixed African ancestry, and of 1234 cases and 3090 controls of Latino ancestry, representing the largest such study in these populations to date. Combining results from the samples with African ancestry with summary statistics from the Psychiatric Genomics Consortium (PGC) study of schizophrenia yielded seven newly genome-wide significant loci, and we identified an additional eight loci by incorporating the results from samples with Latino ancestry. Leveraging population differences in patterns of linkage disequilibrium, we achieve improved fine-mapping resolution at 22 previously reported and 4 newly significant loci. Polygenic risk score profiling revealed improved prediction based on trans-ancestry meta-analysis results for admixed African (Nagelkerke’s R2 = 0.032; liability R2 = 0.017; P −52), Latino (Nagelkerke’s R2 = 0.089; liability R2 = 0.021; P −58), and European individuals (Nagelkerke’s R2 = 0.089; liability R2 = 0.037; P −113), further highlighting the advantages of incorporating data from diverse human populations.

Genome-wide association studies (GWASs) have focused primarily on populations of European descent, but it is essential that diverse populations become better represented. Increasing diversity among study participants will advance our understanding of genetic architecture in all populations and ensure that genetic research is broadly applicable. To facilitate and promote research in multi-ancestry and admixed cohorts, we outline key methodological considerations and highlight opportunities, challenges, solutions, and areas in need of development. Despite the perception that analyzing genetic data from diverse populations is difficult, it is scientifically and ethically imperative, and there is an expanding analytical toolbox to do it well.

Over the past 50 years, it has been increasingly evident that there are population differences in bone mass and the risk of osteoporosis. In the United States, many studies have reported a lower prevalence of osteoporosis in African Americans compared with people of European descent. If we trace the trajectory of changes in lifeways from the earliest migrations of early Homo out of Africa over the past two million years or so, to include lower vitamin D levels in higher latitudes; more meat in the diet; increasing sedentism; and a longer lifespan/longer postmenopausal period, it is not surprising that osteoporosis occurs more frequently in populations of European descent. While many scholars have explored the apparent "paradox" of higher bone mass, lower vitamin D levels, and higher parathyroid hormone levels among African Americans, this brief review of evolutionary shifts that affected our species may change the approach to understanding the current population differences in the United States.

PURPOSE The purpose was to identify factors associated with older glaucoma patients' knowledge of, perceptions of, and predispositions for telemedicine use. MATERIALS AND METHODS Established patients age 60 years and above with a diagnosis of primary open-angle glaucoma, glaucoma suspect, or ocular hypertension followed by a glaucoma fellowship-trained ophthalmologist were enrolled in the study at an academic, urban, tertiary referral eye clinic. Enrolled patients were administered a Life Space Questionnaire (LSQ), scored 0 to 9, and Preferences for Telemedicine Questionnaire (PTQ), a Likert scale validated tool. χ testing analyzed PTQ responses by age, race, education, employment status, LSQ score, and distance traveled from home address to clinic. A Mann-Whitney U test was used to compare PTQ responses by visual field index and visual acuity for the better and worse eye. RESULTS Of 110 patients enrolled, 71% of patients agreed or were neutral to receiving telediagnosis and 74% of patients agreed or were neutral to receiving teleintervention. Patients aged 60 to 69 years compared with those 70 and above had significantly greater knowledge about types of telemedicine: telediagnosis (53% vs. 31%, P=0.02), teleintervention (49% vs. 24%, P=0.006), teletriage (80% vs. 47%, P=0.0004), and telemonitoring (55% vs. 27%, P=0.003). Patients of European descent had significantly more knowledge about teletriage compared with those of non-European descent (72% vs. 53%, P=0.04). Patients with more education (>high school) compared with those with less education (≤high school) had more knowledge about telemedicine (39% vs. 16%, P=0.007) and all the uses of it: telediagnosis (61% vs. 45%, P

SUMMARY Atkins et al conducted a study examining the community incidence of hepatic malignancy in 451,186 UK Biobank participants of European ancestry, and stratified by carriage of C282Y and H63D variants in the HFE gene (JAMA 2020;324:2048-57). This study has its background in exploring the clinical penetrance of HFE Hemochromatosis. The commonest cause of HFE Hemochromatosis is C282Y homozygosity, which affects 0.5-0.6% of individuals of northern European descent. Whilst studies prior to discovery of the underlying genetic defect reported a significant association of clinically diagnosed Hemochromatosis with liver disease and liver cancer, there was limited contemporary data reporting liver-related outcomes, thus justifying the current population study.

Comparatively little is known about the content and form of family memory among Pākehā (New Zealanders of European descent) in contrast to the centrality of whakapapa/genealogy in mātauranga Māori. To address this lacuna, the Marsden-funded research project “The Missing Link” recorded oral history interviews with sixty multigenerational families descended from European migrants who arrived in New Zealand before 1914. We asked our participants what they knew about their family past, the stories that had been passed down, and why particular ancestors interested them. The analysis of these oral history interviews is in progress. This article focuses on the decision to employ a mixed methods research methodology, including an analytical conceptual framework drawn from memory studies, and draws some preliminary conclusions regarding the Pākehā family as a mnemonic community.

Background Posttraumatic stress disorder (PTSD) often co-occurs with alcohol consumption (AC) and alcohol use disorder (AUD). However, it is unknown whether the same etiologic influences that underlie PTSD co-occurring with AUD are those that underlie PTSD and AC individually. Methods This study used large-scale genome-wide association study (GWAS) data to test whether PTSD and drinks per week [DPW]/AUD are causally related to one another, and, if so, whether PTSD precedes DPW/AUD and/or vice versa. We used Mendelian Randomization methods to analyze European ancestry GWAS summary statistics from the Psychiatric Genomics Consortium (PGC; PTSD), GWAS & Sequencing Consortium of Alcohol and Nicotine Use (GSCAN; DPW), and the Million Veteran Program (MVP; AUD). Results PTSD exerted a potentially causal effect on AUD (β = 0.039, SE = 0.014, p = 0.005), but not on DPW (β = 0.002, SE = 0.003, p = 0.414). Additionally, neither DPW (β = 0.019, SE = 0.041, p = 0.637) nor AUD (β = 8.87 × 10-4 , SE = 0.001, p = 0.441) exerted a causal effect on PTSD. Conclusions These findings are consistent with the self-medication model, in which individuals misuse alcohol to cope with aversive trauma-related symptoms. These findings extend latent analysis and molecular findings of shared and correlated risk between PTSD and alcohol phenotypes. Given the health behaviors associated with these phenotypes, these findings are important in that they suggest groups to prioritize for prevention efforts. Further, they provide a rationale for future preclinical and clinical studies examining the biological mechanisms by which PTSD may impact AUD.

UNLABELLED: Background and Objective; Genetic risk factors for childhood cancer may also influence facial morphology. 3D photography can be used in the recognition of differences in face shape among individuals. In previous research, 3D facial photography was used to identify increased facial asymmetry and greater deviation from normal facial morphology in a group of individuals with distinct morphological features who had childhood cancer compared to healthy controls. In this study, we aim to determine whether there is a difference in facial morphology between children with cancer without previously selected morphological features and healthy controls, detected with 3D facial photography. METHODS: Facial 3D photographic images were obtained of children with a newly diagnosed malignancy. The resulting sample comprised 13 different cancer types. Patients were excluded if they had a known genetic cause of the cancer. Patients were compared to healthy controls, matched for sex, age and ethnic background. The degree of asymmetry and overall deviation of an individual's face from an age and sex typical control face were measured. RESULTS: A total of 163 patients of European descent were included. No significant difference in asymmetry between patients and controls could be identified. On average, patients deviated more from an age and sex typical face than the controls. CONCLUSION: This study shows that children with cancer deviate more than controls, possibly suggesting a higher prevalence of genetic anomalies within this group. The results suggest that this is not sufficient to discriminate patients from controls. Further research is necessary to explore the patterns of individual variation among the overall deviation of patients and controls. The open access fees have been paid for this paper, so the paper is open-access in this normally closed-access journal ispartof: Computer Methods And Programs In Biomedicine vol:205 ispartof: location:Ireland status: Published online

Multiple sclerosis (MS) is an autoimmune disorder influenced by genetic and environmental factors. Many studies have provided insights into genetic factors’ contribution to MS via large-scale genome-wide association study (GWAS) datasets. However, genetic variants identified to date do not adequately explain genetic risks for MS. This study hypothesized that novel MS risk genes could be identified by analyzing the MS-GWAS dataset using gene-based tests. We analyzed a GWAS dataset consisting of 9,772 MS cases and 17,376 healthy controls of European descent. We performed gene-based tests of 464,357 autosomal single nucleotide polymorphisms (SNPs) using two methods (PLINK and VEGAS2) and identified 28 shared genes satisfied p-value < 4.56 × 10–6. In further gene expression analysis, ten of the 28 genes were significantly differentially expressed in the MS case-control gene expression omnibus (GEO) database. GALC and HLA-DOB showed the most prominent differences in gene expression (two- and three-fold, respectively) between MS patients and healthy controls. In conclusion, our results reveal more information about MS hereditary characteristics and provide a basis for further studies.

Cystic fibrosis (CF) commonly affects those of European descent; however, it can also be found in those of Asian, African, and Caribbean descent. Patients with CF may have significant lung disease, and their perioperative management can be challenging for the anesthesiologist. In this case report, we describe the use of serratus anterior plane block (SAPB) and IV sedation as an alternative to general anesthesia with an endotracheal tube in a patient with CF pulmonary exacerbation presenting to the operating room for a video-assisted thoracic surgery (VATS).

Osteoporosis is a common skeletal disease, affecting ~200 million people around the world. As a complex disease, osteoporosis is influenced by many factors, including diet (e.g. calcium and protein intake), physical activity, endocrine status, coexisting diseases and genetic factors. In this review, we first summarize the discovery from genome-wide association studies (GWASs) in the bone field in the last 12 years. To date, GWASs and meta-analyses have discovered hundreds of loci that are associated with bone mineral density (BMD), osteoporosis, and osteoporotic fractures. However, the GWAS approach has sometimes been criticized because of the small effect size of the discovered variants and the mystery of missing heritability, these two questions could be partially explained by the newly raised conceptual models, such as omnigenic model and natural selection. Finally, we introduce the clinical use of GWAS findings in the bone field, such as the identification of causal clinical risk factors, the development of drug targets and disease prediction. Despite the fruitful GWAS discoveries in the bone field, most of these GWAS participants were of European descent, and more genetic studies should be carried out in other ethnic populations to benefit disease prediction in the corresponding population.

Polymyalgia rheumatica (PMR) is a common inflammatory disease found in people older than 50 years of Northern European descent. It is characterized by pain and stiffness in the shoulders, arms, hips, and neck. Relapses are common in patients with PMR.This review describes when and how relapses occur in patients with PMR. Potential predisposing factors associated with relapses and management are also discussed. An extensive literature search on the PubMed database was conducted for publications on 'polymyalgia rheumatica' AND 'relapses' AND 'risk factors'.Relapses are common in PMR being observed in approximately half of the patients. They often occur when the dose of prednisone is below 5-7.5 mg/day. The speed of glucocorticoid tapering is considered to be the main factor influencing the development of relapses in isolated PMRs. In addition, a genetic component may favor the presence of relapses in isolated PMRs. HLA-DRB1*0401 alleles were associated with an increased risk of relapse. An implication of the IL-6 promoter -174 G/C polymorphism and the GG241 ICAM-1 genotype was also reported. With regard to serological biomarkers, elevated levels of angiopoietin-2 were associated with an unfavorable course of PMR. Methotrexate and anti-IL6 receptor antibody tocilizumab may be required in PMR patients with multiple relapses.

To identify rare variants associated with prostate cancer (PrCa) susceptibility and better characterize the mechanisms and cumulative disease risk associated with common risk variants, we conducted an integrated study of PrCa genetic etiology in two cohorts using custom genotyping microarrays, large imputation reference panels, and functional annotation approaches. Specifically, 11,984 men (6,196 PrCa cases, 5,788 controls) of European ancestry from Northern California Kaiser Permanente were genotyped and meta-analyzed with 196,269 men of European ancestry (7,917 PrCa cases, 188,352 controls) from the UK Biobank. Three novel loci, including two rare variants (European ancestry minor allele frequency < 0.01, at 3p21.31 and 8p12), were significant genome-wide in a meta-analysis. Gene-based rare variant tests implicated a known PrCa gene (HOXB13), as well as a novel candidate gene (ILDR1), which encodes a receptor highly expressed in prostate tissue and is related to the B7/CD28 family of T cell immune checkpoint markers. Haplotypic patterns of long-range linkage disequilibrium were observed for rare genetic variants at HOXB13 and other loci, reflecting their evolutionary history. Additionally, a polygenic risk score (PRS) of 188 PrCa variants was strongly associated with risk (90th vs. 40–60th percentile OR = 2.62, P = 2.55*10(−191)). Many of the 188 variants exhibited functional signatures of gene expression regulation or transcription factor binding, including a six-fold difference in log-probability of Androgen Receptor binding at the variant rs2680708 (17q22). Rare variant and PRS associations, with concomitant functional interpretation of risk mechanisms can help clarify the full genetic architecture of PrCa and other complex traits.

Polygenic risk scores (PRS) have attenuated cross-population predictive performance. As existing genome-wide association studies (GWAS) were predominantly conducted in individuals of European descent, the limited transferability of PRS reduces its clinical value in non-European populations and may exacerbate healthcare disparities. Recent efforts to level ancestry imbalance in genomic research have expanded the scale of non-European GWAS, although most of them remain under-powered. Here we present a novel PRS construction method, PRS-CSx, which improves cross-population polygenic prediction by integrating GWAS summary statistics from multiple populations. PRS-CSx couples genetic effects across populations via a shared continuous shrinkage prior, enabling more accurate effect size estimation by sharing information between summary statistics and leveraging linkage disequilibrium (LD) diversity across discovery samples, while inheriting computational efficiency and robustness from PRS-CS. We show that PRS-CSx outperforms alternative methods across traits with a wide range of genetic architectures, cross-population genetic overlaps and discovery GWAS sample sizes in simulations, and improves the prediction of quantitative traits and schizophrenia risk in non-European populations.

The work was partially supported by Fondo de Investigaciones Sanitarias (FIS), Instituto de Salud Carlos III, Spain (PI061614, PI11/01542, PI0902102, PI12/01635, PI12/00815, PI15/01573, PI18/01347); Red Temática de Investigación Cooperativa en Cáncer, Spain (RD12/0036/0034, RD12/0036/ 0050, RD12/0036/0073); Spanish Ministerio de Ciencia, Innovación y Universidades (BFU2017-85926-P), López de Maturana, E., Rodríguez, J.A., Alonso, L., Lao, O., Molina-Montes, E., Martín-Antoniano, I.A., Gómez-Rubio, P., Lawlor, R., Carrato, A., Hidalgo, M., Iglesias, M., Molero, X., Löhr, M., Michalski, C., Perea, J., O’Rorke, M., Barberà, V.M., Tardón, A., Farré, A., Muñoz-Bellvís, L., Crnogorac-Jurcevic, T., Domínguez-Muñoz, E., Gress, T., Greenhalf, W., Sharp, L., Arnes, L., Cecchini, L., Balsells, J., Costello, E., Ilzarbe, L., Kleeff, J., Kong, B., Márquez, M., Mora, J., O’Driscoll, D., Scarpa, A., Ye, W., Yu, J., García-Closas, M., Kogevinas, M., Rothman, N., Silverman, D.T., Albanes, D., Arslan, A.A., Beane-Freeman, L., Bracci, P.M., Brennan, P., Bueno-de-Mesquita, B., Buring, J., Canzian, F., Du, M., Gallinger, S., Gaziano, J.M., Goodman, P.J., Gunter, M., LeMarchand, L., Li, D., Neale, R.E., Peters, U., Petersen, G.M., Risch, H.A., Sánchez, M.J., Shu, X.-O., Thornquist, M.D., Visvanathan, K., Zheng, W., Chanock, S.J., Easton, D., Wolpin, B.M., Stolzenberg-Solomon, R.Z., Klein, A.P., Amundadottir, L.T., Marti-Renom, M.A., Real, F.X., Malats, N., PanGenEU Investigators, SBC/EPICURO Investigators

Facial skin coloration signals information about an individual and plays an important role in social interactions and mate choice, due its putative association with health, attractiveness, and age. Whether skin coloration as an evolutionary significant cue is universal or specific to a particular culture is unclear and current evidence on the universality of skin color as a cue to health and attractiveness are equivocal. The current study used 80 calibrated, high-resolution, non-manipulated images of real human faces, either of Chinese or western European descent, which were rated in terms of attractiveness, healthiness, and perceived age by 44 observers, 22 western European (13 male; mean age ± SD = 24.27 ± 5.30) and 22 Chinese (7 male; mean age ± SD = 26.05 ± 3.96) observers. To elucidate the associations between skin coloration and these perceptual ratings and whether these associations are modulated by observer or image ethnicity, a linear mixed-effect model was setup with skin lightness (L*; CIELAB), redness (a*) and yellowness (b*), observer and image ethnicity as independent variables and perceived attractiveness, healthiness, and estimated age as dependent variables. We found robust positive associations between facial skin lightness (L*) and attractiveness, healthiness, and youthfulness, but only when Chinese observers judge facial images of their own ethnicity. Observers of European descent, on the other hand, associated an increase in yellowness(b*) with greater attractiveness and healthiness in Chinese facial images. We find no evidence that facial redness is positively associated with these attributes; instead, an increase in redness (a*) is associated with an increase in the estimated age of European facial images. We conclude that observers of both ethnicities make use of skin color and lightness to rate attractiveness, healthiness, and perceived age, but to a lesser degree than previously thought. Furthermore, these coloration cues are not universal and are utilized differently within the Chinese and western European ethnic groups. Our study adds to the growing body of work demonstrating the importance of skin color manipulations within an evolutionary meaningful parameter space, ideally using realistic skin models based on physical parameters.

The complete understanding of the genomic contribution to complex traits, diseases, and response to treatments, as well as genomic medicine application to the well-being of all humans will be achieved through the global variome that encompasses fine-scale genetic diversity. Despite significant efforts in recent years, uneven representation still characterizes genomic resources and among the underrepresented European populations are the Western Balkans including the Serbian population. Our research addresses this gap and presents the first ever targeted sequencing dataset of variants in clinically relevant genes. By measuring population differentiation and applying the Principal Component and Admixture analysis we demonstrated that the Serbian population differs little from other European populations, yet we identified several novel and more frequent variants that appear as its unique genetic determinants. We explored thoroughly the functional impact of frequent variants and its correlation with the health burden of the population of Serbia based on a sample of 144 individuals. Our variants catalogue improves the understanding of genetics of modern Serbia, contributes to research on ancestry, and aids in improvements of well-being and health equity. In addition, this resource may also be applicable in neighboring regions and valuable in worldwide functional analyses of genetic variants in individuals of European descent.

Introduction: Cystic fibrosis (CF), the most common life-shortening inherited disorder in people of European descent, also occurs in other ethnicities. The identification of the disease, the isolat...

In Ethiopia, a breast cancer diagnosis is associated with a prognosis significantly worse than that of Europe and the US. Further, patients presenting with breast cancer in Ethiopia are far younger, on average, and patients are typically diagnosed at very late stages, relative to breast cancer patients of European descent. Emerging data suggest that a large proportion of Ethiopian patients have hormone-positive (ER +) breast cancer. This is surprising given 1) the aggressive nature of the disease, 2) that African Americans with breast cancer frequently have triple negative breast cancer (TNBC), and 3) these patients typically receive chemotherapy, not hormone-targeting drugs. To further examine the similarity of Ethiopian breast tumors to those of African Americans or of those of European descent, we sequenced matched normal and tumor tissue from Ethiopian patients from a small pilot collection. We identified mutations in 615 genes across all three patients, unique to the tumor tissue. Across this analysis, we found far more mutations shared between Ethiopian patient tissue and White patients (103) than we did comparing to African Americans (3). Several mutations were found in extracellular matrix encoding genes with known roles in tumor cell growth and metastasis. We suggest future mechanistic studies on this disease focus on these genes first, toward finding new treatment strategies for breast cancer patients in Ethiopia.

BackgroundGenetic studies of biomedical phenotypes in underrepresented populations identify disproportionate numbers of novel associations. However, current genomics infrastructure--including most genotyping arrays and sequenced reference panels--best serves populations of European descent. A critical step for facilitating genetic studies in underrepresented populations is to ensure that genetic technologies accurately capture variation in all populations. Here, we quantify the accuracy of low-coverage sequencing in diverse African populations.ResultsWe sequenced the whole genomes of 91 individuals to high-coverage (≥20X) from the Neuropsychiatric Genetics of African Population-Psychosis (NeuroGAP-Psychosis) study, in which participants were recruited from Ethiopia, Kenya, South Africa, and Uganda. We empirically tested two data generation strategies, GWAS arrays versus low-coverage sequencing, by calculating the concordance of imputed variants from these technologies with those from deep whole genome sequencing data. We show that low-coverage sequencing at a depth of ≥4X captures variants of all frequencies more accurately than all commonly used GWAS arrays investigated and at a comparable cost. Lower depths of sequencing (0.5-1X) performed comparable to commonly used low-density GWAS arrays. Low-coverage sequencing is also sensitive to novel variation, with 4X sequencing detecting 45% of singletons and 95% of common variants identified in high-coverage African whole genomes.ConclusionThese results indicate that low-coverage sequencing approaches surmount the problems induced by the ascertainment of common genotyping arrays, including those that capture variation most common in Europeans and Africans. Low-coverage sequencing effectively identifies novel variation (particularly in underrepresented populations), and presents opportunities to enhance variant discovery at a similar cost to traditional approaches.

ObjectiveTo explore sexually transmitted infection (STI) clinic client attitudes and preferences towards STI vaccines and STI vaccine programming in an urban clinic setting.MethodsA 31-item questionnaire was administered during check-in by clinic clerical staff at two STI clinics in Vancouver, Canada. Demographic characteristics and preferences were summarised descriptively. Multivariable logistic regression models to assess factors associated with STI vaccine interest (reported as ORs) were constructed using a priori clinically relevant variables and factors significant at p≤0.05 in bivariate analysis.Results293 surveys were included in analysis. 71.3% of respondents identified as male, 80.5% had college level education or higher and 52.9% identified as white/of European descent. The median age was 33. 86.5% of respondents reported they would be interested in receiving an STI vaccine, with a primary motivator to protect oneself. Bivariate analysis indicated several factors associated with vaccine interest, with differences for each infection. After adjusting for other variables, willingness to pay for an STI vaccine (OR=3.83, 95% CI 1.29 to 11.38, p=0.02) remained a significant factor for syphilis vaccine interest and intent to engage in future positive health behaviours remained a significant factor for chlamydia (OR=5.94, 95% CI 1.56 to 22.60, p=0.01) and gonorrhoea (OR=5.13, 95% CI 1.45 to 18.07, p=0.01) vaccine interest.ConclusionRespondents expressed a strong willingness to receive STI vaccines. These valuable findings will inform for eventual STI vaccine programme planning and implementation.

In Ethiopia, a breast cancer diagnosis is associated with a prognosis significantly worse than that of Europe and the US. Further, patients presenting with breast cancer in Ethiopia are far younger, on average, and patients are typically diagnosed at very late stages, relative to breast cancer patients of European descent. Emerging data suggest that a large proportion of Ethiopian patients have hormone-positive (ER+) breast cancer. This is surprising given (1) that patients have late-stage breast cancer at the time of diagnosis, (2) that African Americans with breast cancer frequently have triple negative breast cancer (TNBC), and (3) these patients typically receive chemotherapy, not hormone-targeting drugs. To further examine the similarity of Ethiopian breast tumors to those of African Americans or of those of European descent, we sequenced matched tumor and normal adjacent tissue from Ethiopian patients from a small pilot collection. We identified mutations in 615 genes across all three patients, unique to the tumor tissue. Across this analysis, we found far more mutations shared between Ethiopian patient tissue and that from white patients (103) than we did comparing to African Americans (3). Several mutations were found in extracellular matrix encoding genes with known roles in tumor cell growth and metastasis. We suggest future mechanistic studies on this disease focus on these genes first, toward finding new treatment strategies for breast cancer patients in Ethiopia.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by the progressive degeneration of motor neurons. Recently, genetic variants in GLT8D1 and ARPP21 were associated with ALS in a cohort of European descent. A synergistic relationship was proposed between ALS associated variants in GLT8D1 and ARPP21. We aimed to determine the prevalence of genetic variation in GLT8D1 and ARPP21 in an Australian cohort of familial (n = 81) and sporadic ALS (n = 618) cases using whole-exome and whole-genome sequencing data. No novel mutations were identified in either gene, nor was there significant enrichment of protein-altering sequence variation among ALS cases. GLT8D1 and ARPP21 mutations are not a common cause of ALS in Australian familial and sporadic cohorts.

Ko koe ki tēnā, ko ahau ki tēnai kīwai o te kete (you at that, and I at this handle of the basket). This Māori (New Zealanders of indigenous descent) saying conveys the principle of cooperation-we achieve more through working together, rather than separately. Despite decades of calls to rectify cultural imbalance in conservation, threatened species management still relies overwhelmingly on ideas from Western science and on top-down implementation. Values-based approaches to decision making can be used to integrate indigenous peoples' values into species conservation in a more meaningful way. We used such a values-based method, structured decision making, to develop comanagement of pekapeka (Mystacina tuberculata) (short-tailed bat) and tara iti (Sternula nereis davisae) (Fairy Tern) between Māori and Pākehā (New Zealanders of European descent). We implemented this framework in a series of workshops in which facilitated discussions were used to gather expert knowledge to predict outcomes and make management recommendations. For both species, stakeholders clearly stated their values as fundamental objectives from the start, which allowed alternative strategies to be devised that naturally addressed their diverse values, including mātauranga Māori (Māori knowledge and perspectives). On this shared basis, all partners willingly engaged in the process, and decisions were largely agreed to by all. Most expectations of conflicts between values of Western science and Māori culture were unfounded. Where required, positive compromises were made by jointly developing alternative strategies. The values-based process successfully taha wairua taha tangata (brought both worlds together to achieve the objective) through codeveloped recovery strategies. This approach challenges the traditional model of scientists first preparing management plans focused on biological objectives, then consulting indigenous groups for approval. We recommend values-based approaches, such as structured decision making, as powerful methods for development of comanagement conservation plans between different peoples.Aplicación de un Proceso de Decisiones Basadas en Valores para Facilitar el Comanejo de Especies Amenazadas en Aotearoa Nueva Zelanda Resumen Ko koe ki tēnā, ko ahau ki tēnai kīwai o te kete (tú en ésa y yo en esta asa de la cesta). Este dicho Māori (neozelandeses con ascendencia indígena) expresa el principio de la cooperación - logramos más trabajando juntos que por separado. A pesar de las décadas de peticiones para rectificar el desbalance ambiental que existe en la conservación, el manejo de especies amenazadas todavía depende abrumadoramente de ideas tomadas de la ciencia occidental y en la implementación de arriba-abajo. Los enfoques para la toma de decisiones basados en valores pueden usarse para integrar de manera más significativa los valores de los pueblos indígenas dentro de la conservación de especies. Usamos un método basado en valores, la toma estructurada de decisiones, para desarrollar una estrategia de comanejo del pekapeka (Mystacina tuberculata) (murciélago de cola corta) y el tara iti (Sternula nereis davisae) (charrancito australiano) entre los Māori y los Pākehā (neozelandeses de ascendencia europea). Implementamos este marco de trabajo en una serie de talleres en los cuales se usaron discusiones facilitadas para recabar el conocimiento de los expertos para pronosticar los resultados y realizar recomendaciones de manejo. Para ambas especies, los actores sociales mencionaron claramente a sus valores como objetivos fundamentales desde el inicio, lo que permitió el diseño de estrategias alternativas que consideraran naturalmente estos diferentes valores, incluyendo el mātauranga Māori (conocimiento y perspectivas Māori). Sobre esta base compartida, todos los colaboradores participaron voluntariamente en el proceso y la mayoría estuvo de acuerdo con las decisiones. La mayoría de los conflictos esperados entre la ciencia occidental y la cultura Māori no tuvieron fundamentos. En donde fueron requeridos, se realizaron concesiones positivas mediante el desarrollo conjunto de estrategias alternativas. El proceso basado en valores logró exitosamente taha wairua taha tangata (juntó a ambos mundos para conseguir el objetivo) por medio de estrategias de recuperación desarrolladas en conjunto. Esta estrategia desafía el modelo tradicional de los científicos preparando primero los planes de manejo enfocados en objetivos biológicos para después consultar a los grupos indígenas para que los aprueben. Recomendamos estos enfoques basados en valores, como la toma estructurada de decisiones, como métodos poderosos para el desarrollo de planes de conservación que incluyan el comanejo entre diferentes pueblos y personas.Ko koe ki tēnā, ko ahau ki tēnai kīwai o te kete(你提篮子的一个把手, 我提另一个把手)。这句毛利人(新西兰原住民)的谚语传达了合作的原则--通过共同努力而不是各自为先来实现更高的目标。尽管几十年来人们都在呼吁纠正保护中的文化不平衡, 但濒危物种管理仍然主要依赖于西方科学理念和自上而下的管理措施。应用基于价值观的决策方法可以通过更有意义的方式将原住民的价值观纳入物种保护之中。本研究采用基于价值观的结构化决策方法, 设计了毛利人与欧洲裔的新西兰人对短尾蝠(Mystacina tuberculata)和眼斑燕鸥(Sternula nereis davisae)的共同管理。我们在一系列研讨会中实施了这一框架, 并在这些研讨会中利用促进协商讨论来收集专家知识, 以预测结果和提出管理建议。对这两个物种来说, 利益相关者可以从一开始就清楚地根据其价值观提出基本目标, 这样有助于制定替代策略来自然地处理不同的价值观, 包括毛利文化和观点。以共享为基础使所有合作者都愿意参与这个过程, 且所有决策基本都得到了同意。大多数关于西方科学与毛利文化价值观之间存在冲突的假想都是没有根据的。双方在必要时通过共同制定替代策略来做出了积极和解。这个基于价值观的过程成功地将两个世界结合在一起, 通过共同制定物种恢复战略来实现目标。这一方法挑战了科学家首先准备好生物目标的管理计划, 然后再与原住民群体商议以获得批准的传统模式。我们推荐基于价值观的方法, 如结构化决策, 作为不同民族之间制定管理保护计划的有效方法。【翻译:胡怡思;审校:聂永刚】.