Explore the vast range of titles available.

Gut microbial communities represent one source of human genetic and metabolic diversity. To examine how gut microbiomes differ among human populations, here we characterize bacterial species in fecal samples from 531 individuals, plus the gene content of 110 of them. The cohort encompassed healthy children and adults from the Amazonas of Venezuela, rural Malawi and US metropolitan areas and included mono- and dizygotic twins. Shared features of the functional maturation of the gut microbiome were identified during the first three years of life in all three populations, including age-associated changes in the genes involved in vitamin biosynthesis and metabolism. Pronounced differences in bacterial assemblages and functional gene repertoires were noted between US residents and those in the other two countries. These distinctive features are evident in early infancy as well as adulthood. Our findings underscore the need to consider the microbiome when evaluating human development, nutritional needs, physiological variations and the impact of westernization. The human gut microbiome from a large cohort of more than 500 indivduals living on three continents with three distinct cultures is analysed, emphasizing the effect of host age, diet and environment on the composition and functional repertoire of fecal microbiota. Variation in the human gut microbiome The human gut microbiome is thought to be shaped by both host diet and genetics. Using a sample set of more than 500 individuals belonging to around 150 families from three different countries, Yatsunenko et al . analyse the impact of both factors on the composition and functional repertoire of the fecal microbiota.

Rates of colon cancer are much higher in African Americans (65:100,000) than in rural South Africans (<5:100,000). The higher rates are associated with higher animal protein and fat, and lower fibre consumption, higher colonic secondary bile acids, lower colonic short-chain fatty acid quantities and higher mucosal proliferative biomarkers of cancer risk in otherwise healthy middle-aged volunteers. Here we investigate further the role of fat and fibre in this association. We performed 2-week food exchanges in subjects from the same populations, where African Americans were fed a high-fibre, low-fat African-style diet and rural Africans a high-fat, low-fibre western-style diet, under close supervision. In comparison with their usual diets, the food changes resulted in remarkable reciprocal changes in mucosal biomarkers of cancer risk and in aspects of the microbiota and metabolome known to affect cancer risk, best illustrated by increased saccharolytic fermentation and butyrogenesis, and suppressed secondary bile acid synthesis in the African Americans. African Americans have much higher colon cancer rates than rural South Africans, which is associated with dietary and metabolic differences. Here, O’Keefe et al. show that switching quantities of fat and fibre leads to reciprocal changes in gut microbiota, metabolites and cancer biomarkers.

Pathogenic fungi are increasingly contributing to the global emerging disease burden, threatening biodiversity and imposing increasing costs on ecosystem health, hence steps must be taken to tighten biosecurity worldwide to reduce the rate of fungal disease emergence. The threat from emerging pathogenic fungi Fungal infections have caused widespread damage in crops and dramatic decline in populations of amphibians and bats. In recent years newly emerged pathogenic fungi have been reported in corals, bees and many plant species. In this Review, Matthew Fisher and colleagues warn that human activity is intensifying fungal-disease dispersal by modifying natural ecosystems and creating new opportunities for evolution. Unless steps are taken to reduce the risk of these infectious diseases spreading globally, the authors suggest, fungal infections will cause increasing attrition of biodiversity, with wider implications for human and ecosystem health. The authors' recommendations include better monitoring of emerging diseases, stringent biosecurity controls on international trade and intensified research on the interactions between hosts, pathogens and the environment. The past two decades have seen an increasing number of virulent infectious diseases in natural populations and managed landscapes. In both animals and plants, an unprecedented number of fungal and fungal-like diseases have recently caused some of the most severe die-offs and extinctions ever witnessed in wild species, and are jeopardizing food security. Human activity is intensifying fungal disease dispersal by modifying natural environments and thus creating new opportunities for evolution. We argue that nascent fungal infections will cause increasing attrition of biodiversity, with wider implications for human and ecosystem health, unless steps are taken to tighten biosecurity worldwide.

Estimating the changing burden of malaria disease remains difficult owing to limitations in health reporting systems. Here, we use a transmission model incorporating acquisition and loss of immunity to capture age-specific patterns of disease at different transmission intensities. The model is fitted to age-stratified data from 23 sites in Africa, and we then produce maps and estimates of disease burden. We estimate that in 2010 there were 252 (95% credible interval: 171–353) million cases of malaria in sub-Saharan Africa that active case finding would detect. However, only 34% (12–86%) of these cases would be observed through passive case detection. We estimate that the proportion of all cases of clinical malaria that are in under-fives varies from above 60% at high transmission to below 20% at low transmission. The focus of some interventions towards young children may need to be reconsidered, and should be informed by the current local transmission intensity. Reduction in malaria transmission has changed the age pattern of malaria incidence. This study brings insights into the changes in age distributions of clinical malaria across Africa, with importance for improving within-population targeting of malaria control interventions.

Dan Nicolae, Carole Ober and colleagues report a meta-analysis of genome-wide association studies for asthma in a collection of ethnically diverse North American populations. They identify a newly associated susceptibility locus at PYHIN1 in individuals of African descent. Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1 , TSLP and IL33 , but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1 , with the association being specific to individuals of African descent ( P = 3.9 × 10 −9 ). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma.

Purpose Nonclassic 21-hydroxylase deficiency, a mild form of congenital adrenal hyperplasia (CAH), is estimated to be the most common autosomal recessive condition, with an especially high prevalence in Ashkenazi Jews (3.7% affected, 30.9% carriers), based on a 1985 HLA-B linkage study of affected families. Affected individuals, especially women, may suffer from hyperandrogenism and infertility. State-of-the-art genetic studies have not been done to confirm these remarkable rates. Methods CYP21A2 genotyping was performed in 200 unrelated healthy Ashkenazi Jewish subjects and 200 random US Caucasians who did not self-identify as a specific ethnicity using multiplex minisequencing, real-time polymerase chain reaction and junction site analysis. Results Nonclassic CAH carriership was found similarly in 15% (95% confidence interval (CI): 10.4–20.7) of Ashkenazi Jews and 9.5% (95% CI: 5.8–14.4) of Caucasians ( P =0.13). The proportion of Ashkenazi Jewish nonclassic CAH carriers (0.15 versus 0.309, P <0.0001) and disease affected (0.005 versus 0.037, P =0.009) was not as high as previously reported. The estimated prevalence of nonclassic CAH in Caucasians was 1 in 200 (0.5%, 95% CI: 0.01–2.8). Conclusion Nonclassic CAH is a common condition, regardless of ethnicity, and should be considered with preconception and infertility counseling.

Background: The potential of an increased risk of breast cancer in women with diabetes has been the subject of a great deal of recent research. Methods: A meta-analysis was undertaken using a random effects model to investigate the association between diabetes and breast cancer risk. Results: Thirty-nine independent risk estimates were available from observational epidemiological studies. The summary relative risk (SRR) for breast cancer in women with diabetes was 1.27 (95% confidence interval (CI), 1.16–1.39) with no evidence of publication bias. Prospective studies showed a lower risk (SRR 1.23 (95% CI, 1.12–1.35)) than retrospective studies (SRR 1.36 (95% CI, 1.13–1.63)). Type 1 diabetes, or diabetes in pre-menopausal women, were not associated with risk of breast cancer (SRR 1.00 (95% CI, 0.74–1.35) and SRR 0.86 (95% CI, 0.66–1.12), respectively). Studies adjusting for body mass index (BMI) showed lower estimates (SRR 1.16 (95% CI, 1.08–1.24)) as compared with those studies that were not adjusted for BMI (SRR 1.33 (95% CI, 1.18–1.51)). Conclusion: The risk of breast cancer in women with type 2 diabetes is increased by 27%, a figure that decreased to 16% after adjustment for BMI. No increased risk was seen for women at pre-menopausal ages or with type 1 diabetes.

Depression is a common symptom in patients with Parkinson disease (PD), and is found at higher rates in these individuals than in healthy populations or patients with other neurodegenerative disorders. Aarsland et al . discuss both the course of depression and the mechanisms that may contribute to the enhanced susceptibility to depression in patients with PD. Management strategies to control depression in these individuals are also highlighted. Depression occurs in around 35% of patients with Parkinson disease (PD) and is often persistent. Symptoms of depression can be evident in individuals at the time of diagnosis and might develop in the premotor stage of the disease. The underlying mechanisms of depression in PD are not known in detail, but changes in brain structure, signaling by neurotransmitters, and levels of inflammatory and neurotrophic factors are all suggested to contribute to its development. Psychosocial factors and pain could also have roles in depression. Changes in dopaminergic, noradrenergic and serotonergic systems in patients with PD might help to explain the incidence of depression in these individuals. Antidepressants that have dual serotonergic and noradrenergic effects are the drugs of choice for treating depression in PD. However, antiparkinsonian drugs might have beneficial effects not only on the motor symptoms of disease, but also on a patient's mood. Deep brain stimulation can worsen depression in some patients, but a preliminary study has suggested that transcranial magnetic stimulation could improve symptoms of depression. This Review describes the frequency and course of depression in patients with PD. The mechanisms that underlie depression in this disease are also discussed, and the management strategies for these patients are highlighted. Key Points Depression occurs in around 35% of patients with Parkinson disease (PD) Mild depression is often persistent in patients with PD, and is a risk factor for moderate to severe depression The etiology of depression in PD is not clear, but changes in neurotransmitter (monoaminergic) signaling and limbic Lewy body pathology might contribute The roles of other pathologies (such as cerebrovascular disease) and neurotrophic changes in depression are not known Pramipexole and nortriptyline are the only agents that have shown antidepressant effects in placebo-controlled clinical trials in patients with PD

John Chambers and colleagues report a genome-wide association study for type 2 diabetes in individuals of south Asian ancestry. They identify six loci newly associated with type 2 diabetes. We carried out a genome-wide association study of type-2 diabetes (T2D) in individuals of South Asian ancestry. Our discovery set included 5,561 individuals with T2D (cases) and 14,458 controls drawn from studies in London, Pakistan and Singapore. We identified 20 independent SNPs associated with T2D at P < 10 −4 for testing in a replication sample of 13,170 cases and 25,398 controls, also all of South Asian ancestry. In the combined analysis, we identified common genetic variants at six loci ( GRB14 , ST6GAL1 , VPS26A , HMG20A , AP3S2 and HNF4A ) newly associated with T2D ( P = 4.1 × 10 −8 to P = 1.9 × 10 −11 ). SNPs at GRB14 were also associated with insulin sensitivity ( P = 5.0 × 10 −4 ), and SNPs at ST6GAL1 and HNF4A were also associated with pancreatic beta-cell function ( P = 0.02 and P = 0.001, respectively). Our findings provide additional insight into mechanisms underlying T2D and show the potential for new discovery from genetic association studies in South Asians, a population with increased susceptibility to T2D.

Purpose: Genetic contributions to tinnitus have been difficult to determine due to the heterogeneity of the condition and its broad etiology. Here, we evaluated the genetic and nongenetic influences on self-reported tinnitus from the Swedish Twin Registry (STR). Methods: Cross-sectional data from the STR was obtained. Casewise concordance rates (the risk of one twin being affected given that his/her twin partner has tinnitus) were compared for monozygotic (MZ) and dizygotic (DZ) twin pairs ( N = 10,464 concordant and discordant twin pairs) and heritability coefficients (the proportion of the total variance attributable to genetic factors) were calculated using biometrical model fitting procedures. Results: Stratification of tinnitus cases into subtypes according to laterality (unilateral versus bilateral) revealed that heritability of bilateral tinnitus was 0.56; however, it was 0.27 for unilateral tinnitus. Heritability was greater in men (0.68) than in women (0.41). However, when female pairs younger than 40 years of age were selected, heritability of 0.62 was achieved with negligible effects of shared environment. Conclusion: Unlike unilateral tinnitus, bilateral tinnitus is influenced by genetic factors and might constitute a genetic subtype. Overall, our study provides the initial evidence for a tinnitus phenotype with a genetic influence. Genet Med advance online publication 23 March 2017