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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

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.

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.

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.

Patterns of adoption behaviour are starkly asymmetric across populations. To better understand this phenomenon we conducted a systematic review of transracial adoption and adoption in general. We f ...

The aim of this study was to examine whether the vitamin D level is causally associated with risk of systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA). We performed two-sample Mendelian randomization (MR) analyses using the inverse-variance weighted (IVW), weighted median, and MR-Egger regression methods on publicly available summary statistics datasets using two vitamin D level genome-wide association studies (GWASs) as exposure and SLE and RA GWASs on people of European descent as outcomes. We selected three independent single-nucleotide polymorphisms located at SSTR4 (rs2207173), GC (rs2282679), and NADSYN1 (3829251) with genome-wide significance from two GWASs on vitamin D levels as instrumental variables. The IVW, weighted median, and MR-Egger regression methods yielded no evidence of a causal association between vitamin D level and risk of SLE (beta = 0.032, SE = 0.119, p = 0.789; beta = 0.233, SE = 0.274, p = 0.552; beta = 0.054, SE = 0.125, p = 0.665; respectively) or RA (beta = 0.026, SE = 0.061, p = 0.664; beta = 0.025, SE = 0.065, p = 0.695; beta = 0.025, SE = 0.065, p = 0.695; respectively). In addition, MR-Egger regression revealed directional pleiotropy was unlikely to be biasing the result for SLE (intercept = - 0.058, p = 0.545) or RA (intercept = - 0.027, p = 0.558). The MR estimates from IVW, weighted median, and MR-Egger regression analyses were consistent. MR analysis did not support a causal association between the vitamin D level and SLE or RA.

This article reviews evidence from the literature suggesting that primary open angle glaucoma (POAG) represents a group of heterogeneous diseases with varying clinical features rather than a single disease. A growing body of evidence has been made available recently indicating that POAG behaves differently in different subpopulations. Although normal tension glaucoma has long been regarded as a diagnosis distinct from POAG, a considerable degree of overlap exists in their pathophysiology and clinical characteristics and suggests that intraocular pressure alone is not a reliable means of separating POAG into different subtypes. Meanwhile, POAG patients with initial paracentral visual field defects rather than early peripheral defects more often exhibit systemic vascular dysregulation, regardless of whether their intraocular pressures are high or low. Patients of African and Afro-Caribbean heritage develop a subtype of POAG that manifests at an earlier age, displays a more rapid disease course, and leads to blindness more frequently than do patients of European descent. Recognizing the existence of various POAG subtypes differentiated by factors other than intraocular pressure alone will allow clinicians to diagnose glaucoma more accurately and provide more individualized care.

Breast cancer is the most frequent cancer in women worldwide. It is classified into intrinsic subtypes characterized by different molecular profiles and prognosis. The prevalence of the different intrinsic subtypes varies between population groups. IHC surrogates based on the expression of the estrogen receptor, progesterone receptor, and HER2 have been widely used to study the distribution of intrinsic subtypes in non-Hispanic whites and African Americans, but data are limited for Hispanic/Latina women. Similarly, most studies analyzing gene expression profiles only include women of European descent. This review focuses on studies that describe the distribution of breast cancer subtypes in Hispanic/Latina women and highlights the need for more research in this population. Cancer Epidemiol Biomarkers Prev; 27(1); 3–10. ©2017 AACR.

Nonsyndromic cleft lip with or without cleft palate (nsCL/P) is one of the most common congenital malformation worldwide, and its etiology involves both genetic and environmental factors. Recent genome-wide and targeted genetic studies of nsCL/P have identified numerous genetic risk loci, under the hypothesis of a multiplicative mode of inheritance. The present study investigated whether novel nsCL/P risk loci could be identified by analyzing dominant/recessive genetic effects in single nucleotide polymorphism (SNP) data from genome-wide association studies. For this purpose, a genome-wide investigation of dominant/recessive common SNP effects was performed in our previously published meta-analysis data set. Twenty-four loci were identified as candidate regions. In a subsequent association analysis in an independent study cohort of 224 nsCL/P patients and 986 controls of European descent, none of the loci could be replicated. Therefore, our strategy of identifying novel loci by applying different genetic models did not yield any novel findings, suggesting that recessive/dominant common variation only make a limited contribution to nsCL/P in Europeans. However, we cannot rule out that such effects are present at some of the loci that have previously been identified, or are present in different populations.

The introduction of the genome-wide association study transformed schizophrenia genetics research and has promoted a genome-wide mindset that has stimulated the development of genomic technology, enabling departures from the traditional candidate gene approach. As result, we have witnessed a decade of major discoveries in schizophrenia genetics and the development of genome-wide approaches to the study of copy number variants. These genomic technologies have primarily been applied in populations of European descent. However, more recently both genome-wide association study and copy number variant studies in Asian populations have begun to emerge. In this invited review, we provide concise summaries of the schizophrenia genome-wide association study and copy number variant literature with specific focus on studies conducted in the Japanese population. When applicable, we compare findings observed in the Japanese population with those found in other populations. We conclude with recommendations for future research in schizophrenia genetics, relevant to Japan and beyond.

This article presents an analysis of how scientists are portrayed in the Lebanese national science textbooks. The purpose of this study was twofold. First, to develop a comprehensive analytical framework that can serve as a tool to analyze the image of scientists portrayed in educational resources. Second, to analyze the image of scientists portrayed in the Lebanese national science textbooks that are used in Basic Education. An analytical framework, based on an extensive review of the relevant literature, was constructed that served as a tool for analyzing the textbooks. Based on evidence-based stereotypes, the framework focused on the individual and work-related characteristics of scientists. Fifteen science textbooks were analyzed using both quantitative and qualitative measures. Our analysis of the textbooks showed the presence of a number of stereotypical images. The scientists are predominantly white males of European descent. Non-Western scientists, including Lebanese and/or Arab scientists are mostly absent in the textbooks. In addition, the scientists are portrayed as rational individuals who work alone, who conduct experiments in their labs by following the scientific method, and by operating within Eurocentric paradigms. External factors do not influence their work. They are engaged in an enterprise which is objective, which aims for discovering the truth out there, and which involves dealing with direct evidence. Implications for science education are discussed.

Creating a facial appearance for individuals from the distant past is often highly problematic, even when verified methods are used. This is especially so in the case of non-European individuals, as the reference populations used to estimate the face tend to be heavily biased towards the average facial variation of recent people of European descent. To evaluate the problem, a facial approximation of a young woman from the Late Pleistocene rockshelter of Tham Lod in north-western Thailand was compared against the average facial variation of datasets from recent populations. The analysis indicated that the Tham Lod facial approximation was neither overtly recent in facial morphology, nor overtly European. The case is of particular interest as the Tham Lod individual probably belonged to a population ancestral to extant Australo-Melanesian peoples.

Dupuytren’s disorder is considered a genetic disorder and therefore not covered under workers’ compensation. Personal risk factors include workers of Northern European descent and workers that are older than 50 years. However, new evidence has shown that certain occupational activities may increase the risk of developing this disorder. This article is a review of the literature with a case study. Work-related and personal risk factors are explored, as well as interventions and return to work recommendations.

Contains fulltext : 170602.pdf (Publisher’s version ) (Open Access) Between 2001 and 2012, the number of unrelated donors registered worldwide increased from 7 to 21 million, and the number of public cord blood units increased to over 500,000. We addressed the question of whether this expansion resulted in higher percentages of patients reaching transplantation. Unrelated donor searches were evaluated for 3,124 eligible patients in the Netherlands in two cohorts (2001-2006, n=995; 2007-2012, n=2129), comparing results for patients of Northwestern European and non-Northwestern European origin. Endpoints were 'donor found' and 'transplantation reached'. The substantial growth of the donor inventory over the period studied did not increase the median number of potential unrelated donors (n=7) for non-Northwestern European patients, but almost doubled the number for Northwestern European patients from 42 to 71. Before and after 2007, an unrelated donor or cord blood was identified for 91% and 95%, respectively, of Northwestern European patients and for 65% and 82% of non-Northwestern European patients (P

Dupuytren's contracture is a common disease that principally affects those of northern European descent. It causes a progressive flexion contracture in the digits especially affecting the ulna side of the hand. The prevalence of the disease increases with age and is commoner in men than women. The current treatment is an operative correction of the contracture that generally results in good if not complete correction. However operative release is associated with a high complication rate and although they are mainly minor in nature, recovery following surgery can take many weeks. Dupuytren's disease has a genetic predisposition and as a result recurrence is common following surgery. There is extensive research into the disease to understand the biological basis and to ultimately develop improved treatments that are less invasive and provide a greater disease-free interval.

International audience; Mutations in the sphingomyelin phosphodiesterase 1 (SMPD1) gene were reported to be associated with Parkinson's disease and dementia with Lewy bodies. In the current study, we aimed to evaluate the role of SMPD1 variants in isolated rapid eye movement sleep behavior disorder (iRBD). SMPD1 and its untranslated regions were sequenced using targeted next-generation sequencing in 959 iRBD patients and 1287 controls from European descent. Our study reports no statistically significant association of SMPD1 variants and iRBD. It is hence unlikely that SMPD1 plays a major role in iRBD.

This study underscored the importance of addressing the well-being of college students of Asian descent, because these students had higher rates of depression and lower positive feelings about their ethnic group compared with students of European descent, as measured by the Affirmation subscale of the Ethnic Identity Scale. Affirmation mediated the depression difference between these groups. Within the Asian group, affirmation and depression were inversely correlated, and this relationship was mediated by acculturative stress.

CALR mutations are detected in about 50% of persons of predominately European descent with essential thrombocythemia (ET) or primary myelofibrosis (PMF) with wild-type alleles of JAK2 and MPL. We studied 1088 Chinese with diverse myeloproliferative neoplasms including ET (N=234) and PMF (N=50) without JAK2(V617F) or MPL exon 10 mutations. CALR mutation was detected in 53% (95% CI, 46-60%) of subjects with ET and 56% (95% CI, 41-70%) of subjects with PMF. 152 CALR mutations were identified clustering into 15 types including deletions (N=8), insertions (N=3) and complex indels (N=4). We also identified 9 new mutations. Mean (±SD) mutant allele burden was 31±12% (range, 0.5-69%). Persons with PMF had higher CALR mutant allele burdens than those with ET (38±8% vs. 29±12%; P0.001). Amongst persons with CALR mutations, those with PMF had different clinical features from those with ET. These data may be useful for diagnosing ET and PMF in Chinese who are about 40% of all persons with ET and PMF and for monitoring therapy-response. They also highlight similarities and differences in CALR mutations between Chinese and persons of predominately European descent with these diseases.

Objectives To evaluate the expression of Th1, Th2, and Th17 cytokines in patients with systemic lupus erythematosus (SLE), and verify the association between serum cytokine levels and vitamin D concentration. Methods The sample consisted of 172 patients with SLE. 25-Hydroxyvitamin D (25(OH)D) levels were measured by chemiluminescence and 25(OH)D levels Results One hundred and sixty-one (93.6%) patients were women and 128 (74.4%) were of European descent. Mean patient age was 40.5 ± 13.8 years, and mean age at diagnosis was 31.5 ± 13.4 years. At the time of study entry, patients had a median (IQR) SLEDAI of 2 (1–4) and SLICC of 0 (0–1). Mean 25(OH)D concentration was 25.4 ± 11.04 ng/mL. Fifty-nine (34.3%) patients had a vitamin D deficiency. No statistically significant associations were identified between cytokine and vitamin D levels. The most significant finding was a positive correlation between INF-α levels and SLEDAI ( rs = 0.22, p = 0.04). Conclusion Although vitamin D deficiencies are highly prevalent in patients with SLE, vitamin D levels were not significantly associated with patient cytokine profiles. The positive correlation between IFN-α levels and SLEDAI showed in this study corroborates other findings in the literature. The present results did not replicate those of in vitro studies of the effect of vitamin D levels on cytokine profiles. Placebo-controlled intervention trials of the effect of vitamin D on cytokine profiles are still required before any definitive conclusions can be drawn regarding the association between these variables.

PURPOSE To determine how accurately a ray through the anterior and posterior ethmoidal foramina predicts the location of the optic foramen. METHODS Dried, well-preserved, complete human skulls without bony defects belonging to the Hamann-Todd osteological collection of the Cleveland Museum of Natural History were examined. Photography was performed and a ray was drawn on orbit photographs extending through the center of the anterior and posterior ethmoidal foramina toward the optic canal. The location of the ray at the anterior aspect of the optic canal was recorded. RESULTS Sixty-six total orbits were examined from 36 skulls with 6 skulls with only unilateral data. Thirty-eight orbits were of African descent and 28 were of European descent with an average age 45.25 years (range = 19-89 years). The anterior-posterior ethmoidal foramen ray extended superior (12/66), through (53/66), and inferior (1/66) to the optic canal. Of those rays passing through the optic canal, 32/53 (60%) passed through the upper one-third, 19/53 (36%) passed through the middle one-third, and 2/53 (4%) passed through the lower one-third of the optic canal. CONCLUSIONS The anterior-posterior ethmoidal foramen ray highly predicts the superior aspect of the optic canal. This information can guide medial orbital wall surgery.

There are a small group of mature adults in their 50s and 60s, members of the so-called third age that arrive at the door for psychotherapy. As clients, they want to explore an overwhelming sense of being dis-located in space and time, and at odds with where they find themselves living. They have a deep and profound sense of not belonging and of being rootless. These older, white, adults are the baby-boomers of post World War II, and I refer to them as the adult children of the colonies because they are of European descent but born in the colonies of Africa. This paper describes the experiences of two clients, Robert and Caitlin, who find themselves feeling progressively psychically dis-located in South Africa and confronting not only their limited future in terms of impending death, but confronting existential givens of life that prevent them at this late stage of life from returning home to their ancestral lands. They present a unique group of older adult clients, and like fish out of water, they have no sense of belonging to Africa, and as a result, they experience a range of emotions such as despair and depression with a concomitant sense of fragmented identities. Discussion of the cases ensues and includes the concept of intergenerational transmission of trauma, fragmented identities, and belonging as linked to ancestral lands.

Attention Deficit Hyperactivity Disorder(ADHD) is a highly heritable childhood behavioural disorder affecting 5% of school-age children and 2.5% of adults worldwide. Recently, the Psychiatric Genomics Consortium and iPSYCH successfully identified 12 independent loci significantly associated with ADHD in genome-wide meta-analysis of 20,183 ADHD cases and 35,191 controls of predominantly European ancestry (Demontis et al., in preparation). We expand upon this result by incorporating additional samples of non-European ancestry in order to advance genome-wide variant discovery, improve fine-mapping, and evaluate transferability of ADHD risk prediction across ancestries. To date, most genome-wide association studies (GWAS) have focused on samples of European descent. As a result, current GWAS results are overly enriched for alleles that are common in European populations, which can yield unexpected biases when trying to evaluate those risk variants in other populations (Martin et al., 2017). Incorporating diverse populations in GWAS can not only address this bias, but improve the resolution of fine-mapping for GWAS effects by allowing comparison of the effects across different LD structures in samples of different ancestry (Zaitlen et al., 2010). Therefore, the current analysis focuses on GWAS of ADHD in non-European ancestry samples for comparison to the existing European-ancestry GWAS results. In particular, we perform GWAS for more than 4,000 ADHD cases and ancestry-matched controls, including cohorts from China and Brazil, and individuals of admixed and predominantly non-European ancestry from large population samples of Denmark and United Kingdom. Logistic mixed models (Chen et al., 2016) are used to analyze the diverse admixed samples while correctly controlling for sample ascertainment. These results are then combined with the European-ancestry GWAS in order to identify additional ADHD-associated loci through trans-ethnic meta-analysis. Fine-mapping is also performed for the 12 previously identified loci. In addition to the trans-ethnic meta-analysis, we also evaluate the transferability of the European ancestry results to other populations using polygenic scores computed from the European ancestry GWAS results as the discovery sample. We quantify the reduced performance of the polygenic scores in non-European ancestry individuals compared to other independent European-ancestry cohorts.

We tested 357 Chinese with primary myelofibrosis for mutations in CALR, JAK2 and MPL. CALR mutations were detected in 76 subjects (21%). There were 24 (32%) type-1 (L367fs*46) and 49 (64%) type-2 (K385fs*47) mutations. Seventy-two of 168 subjects (43%) without a JAK2 or MPL mutation had a CALR mutation. Subjects with a type-2 CALR mutation had lower hemoglobin concentrations (P=0.001), lower WBC counts (P450 × 109/L, P=0.042) and no splenomegaly (P=0.004). Type-2 CALR mutation or no detectable mutation was an independent high-risk factor for survival in multivariate analyses. These data suggest the ratio between type-1 and type-2 mutations is reversed in Chinese with primary myelofibrosis compared with populations of subjects with primary myelofibrosis of predominately European descent. The unfavorable prognostic impact of CALR mutations in Chinese with primary myelofibrosis is only seen in those with type-2 mutations. These data underscore the need to evaluate the prognostic impact of genetic mutations in different populations.

We report a term male infant born to parents of Danish descent, who on the second day of life developed jaundice peaking at 67 hours and decreasing on applied double-sided phototherapy. In the weeks following, the infant showed signs of ongoing hemolysis. Laboratory tests showed very low glucose-6-phosphate dehydrogenase (G6PD) enzymatic activity, and sequencing of the G6PD gene revealed a previously uncharacterized missense mutation c. 592 C>A (Arg198Ser). Oral DNA from the infant had the same G6PD mutation, suggesting a spontaneous maternal germline mutation as the mutation was not observed in leukocytes from the mother.

AimIt is not known whether nutritional status differs between Australian Aboriginal and non Aboriginal haemodialysis subjects. The aim of this study was to investigate the nutritional status of Australian Aboriginal and non-Aboriginal haemodialysis subjects at satellite dialysis centres. MethodSeventy-six (25 Aboriginal, 51 non-Aboriginal) prevalent haemodialysis patients were enrolled in a 3-month cross-sectional study. Each month anthropometric and biochemical measurements were collected. Nutritional status (diet history, patient-generated subjective global assessment (PG-SGA), handgrip strength) was assessed by a dietitian. ResultsPG-SGA detected mild to moderate malnutrition in 35% of Aboriginal patients and 25% of non-Aboriginal patients. The overall physical rating on the PG-SGA was significantly higher in Aboriginal patients, indicating the presence of a greater deficit in muscle mass in this population. Inter-dialytic weight gain was significantly greater in Aboriginal subjects (median [range] 3.0 [2.1-5.7] vs 2.5 [-0.3-5.0] kg, P 1.6 and median normalized protein catabolic rate 1.5). Difficulties were encountered in obtaining dietary information from Aboriginal subjects using the diet history method. ConclusionSubjects had acceptable parameters of dialysis adequacy; however, 35% had evidence of malnutrition. Further research should focus on establishing a knowledge base for the nutritional management for Aboriginal dialysis subjects, and the development of a validated individual dietary assessment method for use in this population group. Summary at a Glance In this first study of dietetic assessment of Australian Aboriginal maintenance haemodialysis subjects, 35% showed evidence of malnutrition despite adequate dialysis. This paper illustrates the need for more research in an over-represented haemodialysis patient population.

This study suggests that generational affiliation is significant in explaining distinctive ethnic perceptions among dominant groups. In Israel, the Ashkenazim, Jews of European descent, constitute the political, social, and economic elite. In-depth interviews with two generations of Ashkenazim showed similarities in ethnic perceptions, but also revealed important differences among the two generations. For the older group, Ashkenaziness is both an ethnicity-free norm of Israeliness and a product of European culture performed by both the marking and unmarking of cultural boundaries. The younger group, on the other hand, self-identifies as Ashkenazi, but interprets Ashkenaziness as a thin ethnicity and primarily a position of social power. This evolution in ethnic perceptions is explained by the historical specific interface of three factors: dominant discursive orders of the era, state institutions and policies, and the encounter with the “other.”

We describe three unrelated patients of European descent carrying an overlapping 3q26.33–3q27.2 microdeletion who share common clinical features: neonatal hypotonia, severe feeding problems, specific facial features, abnormal dentition, recurrent upper airways infections, developmental delay and severe growth impairment. One of the patients carries a smaller deletion and presents a milder phenotype. We propose that 3q26.33–3q27.2 microdeletion may represent a novel condition caused by the haploinsufficiency of dosage sensitive genes, several of which are involved in brain development.

Idiopathic pulmonary fibrosis (IPF) affects lung parenchyma with progressing fibrosis. In this study, we aimed to replicate MUC5B rs35705950 variants and determine new plausible candidate variants for IPF among four different European populations. We genotyped 26 IPF candidate loci in 165 IPF patients from four European countries, such as Czech Republic (n = 41), Germany (n = 33), Greece (n = 40), France (n = 51), and performed association study comparing observed variant distribution with that obtained in a genetically similar Czech healthy control population (n = 96) described in our earlier data report. A highly significant association for a promoter variant (rs35705950) of mucin encoding MUC5B gene was observed in all IPF populations, individually and combined [odds ratio (95% confidence interval); p-value as 5.23 (8.94-3.06); 1.80 × 10(-11)]. Another non-coding variant, rs7934606 in MUC2 was significant among German patients [2.85 (5.05-1.60); 4.03 × 10(-4)] and combined European IPF cases [2.18 (3.16-1.50); 3.73 × 10(-5)]. The network analysis for these variants indicated gene-gene and gene-phenotype interactions in IPF and lung biology. With replication of MUC5B rs35705950 previously reported in U.S. populations of European descent and indicating other plausible polymorphic variants relevant for IPF, we provide additional reference information for future extended functional and population studies aimed, ideally with inclusion of clinical parameters, at identification of IPF genetic markers.

Aim: To investigate prevalence, time trends and factors associated with rhinitis and rhinoconjunctivitis not related to acute infections in New Zealand. Methods: The International Study of Asthma and Allergies in Childhood (ISAAC) surveyed children aged 6–7 and 13–14 years for symptoms of these conditions. Five New Zealand centres were surveyed on two occasions (Phase One and Phase Three) 8–10 years apart. In Phase Three, questions were included on environmental factors, which might be associated with rhinoconjunctivitis. We report findings related to symptoms of rhinoconjunctivitis among 24 190 New Zealand children. Results: Symptoms of rhinoconjunctivitis in the past year were reported in 11.4% of 6- to 7-year-old children and 18% of 13- to 14-year-old adolescents in Phase Three compared with 9.5 and 19.1%, respectively, in Phase One. Severe symptoms of rhinoconjunctivitis were reported in 0.5% of children and 0.8% of adolescents. Current symptoms were more common in males at 6–7 years and in females of 13–14 years, and Māori and Pacific Island ethnic groups had higher prevalence compared with those of European descent, especially in the older age group. For immigrant children, there was a very strong positive relationship between symptoms and length of time resident in New Zealand, supporting the probable importance of environmental factors. A positive association was found between symptoms and use of paracetamol in infancy or in the last year, and weaker associations were noted for antibiotic use, exercise, and regular pasta ingestion. Conclusions: Further study of environmental factors is recommended.

Little research exists on the body mass index (BMI) values of nineteenth-century Americans of European descent. Examination of a new body mass index data set and robust statistical analysis yields the following conclusion: between 1860 and 1880, BMIs decreased across the distribution; however, after 1880, BMIs in the highest quantiles increased, while those in lower BMI quantiles continued to decrease. Late nineteenth- and early twentieth-century white BMIs increased at older ages in higher quantiles and decreased in lower quantiles, indicating significant net biological disparity by age. During industrialization, white BMIs were lower in Kentucky, Missouri, and urban Philadelphia.

INTRODUCTION: Dupuytren's disease (DD) causes progressive digital flexion contracture and is more common in men of European descent. METHODS: Orthopaedic and plastic surgeons in 12 European countries (the Czech Republic, Denmark, Finland, France, Germany, Hungary, Italy, The Netherlands, Poland, Spain, Sweden and the UK) with3 and30 years experience reviewed the medical charts of five consecutive patients they had treated surgically for DD in 2008. Descriptive statistics are reported. RESULTS: In total, 3,357 patient charts were reviewed. Mean (standard deviation) patient age was 61.9 (10.2) years; 81% were men. At the time of the procedure, 11% of patients were at Tubiana stage Ia (0-20° total flexion); 30%, stage Ib (21-45°); 34%, stage II (46-90°); 17%, stage III (91-135°); and 5%, stage IV (135°). Percutaneous needle fasciotomy was performed in 10%, fasciotomy in 13%, fasciectomy in 69% and dermofasciectomy (DF) in 6% of patients. After surgery, fingers improved a mean of 1.9 Tubiana stages, and 54% of patients had no nodules or contracture. The rate of reported complications during the procedure was 4% overall (11% in patients undergoing DF). The most common postoperative complications reported were haematoma (8%), wound healing complications (6%) and pain (6%). No postoperative complications were reported in 77% of patients. CONCLUSIONS: In this European study of more than 3,000 patients with DD, most patients were diagnosed at Tubiana stage I or II, the majority received fasciectomy and more than half had no nodules or contracture remaining after surgery. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12570-012-0092-z) contains supplementary material, which is available to authorized users.

South-central Pennsylvania, framed by the great folds of the Appalachians to the north and west, by the Mason-Dixon Line to the south, and by the rise of hills that bound the lower Susquehanna River to the east, was claimed by settler-farmers of western European descent during the early and mid-eighteenth century. They utilized river and stream valleys to gain access to the fertile lowlands and rich uplands of the region, following in the steps of surveyors to mark farm boundaries with timber fences cut from the cloak of forest. The social and ecological imprint of these boundary structures has endured for hundreds of years.

Lower than normal leg fat mass and excessive trunk fat mass are predictive of insulin resistance (IR) in obese women of European descent. Whether this regional adiposity relationship applies to moderately overweight women of Chinese descent is undetermined. Thus, the relationship between leg and trunk fat mass and IR of young (22.3 ± 0.3 years) sedentary Australian women of either Chinese (CW; n = 22) or European (EW; n = 36) descent was examined.Subjects underwent a maximal oxygen uptake test, blood draw, and dual energy x-ray absorptiometry to measure body composition. Fasting insulin levels and C-reactive protein (CRP) were assessed by ELISA and IR was calculated by HOMA-IR. Blood lipids and glucose were quantified by an automated enzymatic method (Cholestech LDX, USA).Total, arm, trunk, and leg fat was significantly greater (p0.05) for the EW group, whereas IR was significantly higher for CW. Fasting lipids and glucose were within normal levels for both groups, whereas CRP levels were significantly higher in EW. For EW trunk fat mass was the only variable significantly correlated with IR (r = 0.40, p0.05). In contrast, for CW leg fat mass was significantly correlated with IR (r = − 0.49, p0.05).Greater trunk fat mass was associated with higher IR of Australian women of European descent, whereas smaller leg fat mass was associated with higher IR of women of Chinese descent.

BACKGROUND: Questionnaire-based studies investigating blood donation history rely on the accurate recall of information from participants for results to be valid. This study aimed to retrieve electronic records from a national blood donation service and link them to self-reported history of donation to assess agreement between the two sources. STUDY DESIGN AND METHODS: Between 2004 and 2006, a sample of participants of northern European descent was selected from the Melbourne Collaborative Cohort Study (n = 31,192) to participate in the "HealthIron" study (n = 1438). A total of 1052 participants completed questionnaires that included questions about blood donation history. In 2009, consenting participants' records were linked to the Australian Red Cross Blood Service (ARCBS) to provide information on blood donations made between 1980 and follow-up (2004-2006). Those who commenced blood donation before 1980 were excluded. RESULTS: A total of 718 participants were available for analysis. Of these, 394 (55%) provided signed consent, including 182 (82%) of the 227 participants who self-reported ever donating blood. The two data sources were concordant for 331 (87%) of participants, with a κ statistic of 0.74 (SE, 0.05) indicating a high level of agreement. Participants tended to overstate by a factor of 2.0 (95% confidence interval, 1.7-2.2) the number of donations they had made when compared with ARCBS records. CONCLUSION: Participants in studies assessing self-reported blood donation history are likely to correctly indicate whether or not they have ever donated blood. Quantitative estimates are potentially inaccurate and could benefit from validating a sample of records to quantify the bias.

Prediction of phenotypes from genetic data is considered to be the first practical application of data gained from association studies, with potential importance for medicine and the forensic sciences. Multiple genes and polymorphisms have been found to be associated with variation in human pigmentation. Their analysis enables prediction of blue and brown eye colour with a reasonably high accuracy. More accurate prediction, especially in the case of intermediate eye colours, may require better understanding of gene-gene interactions affecting this polygenic trait. Using multifactor dimensionality reduction and logistic regression methods, a study of gene-gene interactions was conducted based on variation in 11 known pigmentation genes examined in a cohort of 718 individuals of European descent. The study revealed significant interactions of a redundant character between the HERC2 and OCA2 genes affecting determination of hazel eye colour and between HERC2 and SLC24A4 affecting determination of blue eye colour. Our research indicates interactive effects of a synergistic character between HERC2 and OCA2, and also provides evidence for a novel strong synergistic interaction between HERC2 and TYRP1, both affecting determination of green eye colour.

Background Schizophrenia is a chronic and disabling psychiatric disorder affecting about 1% of the world population. While the biological mechanisms of schizophrenia remain largely elusive, much progress has been made in schizophrenia genetics in the past few years, with over 100 genomic loci associated with schizophrenia reported by the recent large-scale genome-wide association study. However, to date, almost all large schizophrenia genetics studies are derived from primarily European descent population, severely limiting our understanding of schizophrenia biology. Methods Here we present a large-scale schizophrenia genetic study, comprising of 12 schizophrenia case-control cohorts from Singapore, Hong Kong, Taiwan, mainland China, Japan, and Indonesia. After quality control, there are 13,760 cases and 16,883 controls available for genome-wide association. A fixed effect meta-analysis across Asian and Caucasian populations was conducted resulting in a combined sample of 46,945 cases and 59,800 controls. A novel fine-mapping algorithm was designed and conducted to identify potential causal variants between Caucasian and Asian samples. Results Twelve loci (p Discussion The reported results consist of amongst the largest collection of Asian GWAS samples to date. Evidence indicates shared biology across major world populations in schizophrenia. Specifically, across the two populations, all known schizophrenia associations were congruent in effect directions, and effect sizes show no significant heterogeneity. Our approach not only serve to improve detection of common variant loci that implicates two major populations in the world, the approach we have undertaken, improved GWA resolution which in turn allows us to better isolate the causal alleles and facilitate the functional interpretation of schizophrenia associations.