Achieving landscape-scale deer management for biodiversity conservation: The need to consider sources and sinks

Hyper-herbivory following predator removal is a global issue. Across North America and Europe, increasing deer numbers are affecting biodiversity and human epidemiology, but effectiveness of deer management in heterogeneous landscapes remains poorly understood. In forest habitats in Europe, deer numbers are rarely assessed and management is mainly based on impacts. Even where managed areas achieve stable or improving impact levels, the extent to which they act as sinks or persist as sources exporting deer to the wider landscape remains unknown. We present a framework to quantify effectiveness of deer management at the landscape scale. Applied across 234 km2 of Eastern England, we assessed management of invasive Reeve’s muntjac (Muntiacus reevesi) and native roe (Capreolus capreolus), measuring deer density (using thermal imaging distance transects 780 km/year), fertility, neonatal survival, and culling to quantify source-sink dynamics over 2008–2010. Despite management that removed 23–40% of the annual population, 1,287 (95% CI: 289–2,680) muntjac and 585 (454–1,533) roe deer dispersed annually into the wider landscape, consistent with their ongoing range expansion. For roe deer, culled individuals comprised fewer young deer than predicted by a Leslie matrix model assuming a closed population, consistent with agedependent emigration. In this landscape, for roe and muntjac, an annual cull of at least 60% and 53%, respectively, is required to offset annual production. Failure to quantify deer numbers and productivity has allowed high density populations to persist as regional sources contributing to range expansion, despite deliberative management programs, and without recognition by managers who considered numbers and impacts to be stable. Reversing an unfavorable condition of woodland biodiversity requires appropriate culls across large contiguous areas, supported by knowledge of deer numbers and fertility

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.Peer reviewe

Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1

Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value < 1 × 10-5) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p < 1 × 10-5). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10-10, odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

A genome-wide association search for type 2 diabetes genes in African Americans.

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations

Deer abundance estimation at landscape-scales in heterogeneous forests

Reliable estimates of deer abundance support effective management of source-sink population dynamics in complex landscapes and improve understanding of the relation between deer density and biodiversity impacts. Performance of distance sampling using thermal imaging of Reeves’ muntjac Muntiacus reevesi and roe deer Capreolus capreolus was examined across 123 km2 of conifer forest in Eastern England, sampling 1567 km in total. For muntjac distance sampling was compared to estimates from drive counts in 2007. For each of three subsequent winters (2008-2010), we compared the magnitude and precision of forest-wide abundance estimated from analytical designs that: i) ignored potential habitat-specific detectability, either with uneven or balanced sampling effort; ii) controlled for sampling effort and/or density among seven forest blocks (mean = 18.8 km2 ± 11.1 SD); iii) accounted for potential movement prior detection; iv) accounted for varying detectability among habitat classes (as a covariate), while controlling for differing densities among blocks. Detectability was further examined in models that stratified to estimate habitat-specific Effective Strip Width (ESW). Estimated muntjac densities from distance sampling were of similar magnitude to estimates from drive counts. Over 2008-2010, we observed 1926 muntjac and 921 roe groups; allowing robust abundance estimation and habitat-specific analysis. ESWs in open habitat were 31% and 27% greater than in mature and 45% and 46% greater than in dense habitat, for roe and muntjac respectively. Although differences in densities among model designs were not large, ignoring block or habitat effects gave higher estimates, while models that accounted for habitat-specific detectability gave lower (-8%) and more precise (38% reduction in CV) estimates (n = 3, muntjac: 5.3-7.5% CV; roe deer: 8.8-12.6% CV). The similarity of density estimates between ungrouped and grouped data and analysis of behaviour of detected deer support the conclusion that distance estimates were not biased by avoidance. We conclude that distance sampling using thermal imaging is a robust and powerful method for estimating deer density. In heterogeneous forest density estimates will be improved by accounting for varying detectability among growth stages or habitats

Relative influence of inter- and intra-specific competition in an ungulate assemblage modified by introductions

Inter-specific competition from introduced and naturally-colonising species has potential to affect resident populations, but demographic consequences for vertebrates have rarely been tested. We tested hypotheses of inter- and intra-specific competition for density, body mass and fertility of adult female roe deer Capreolus capreolus across a heterogeneous forest (195 km 2 ) landscape also occupied by introduced Mediterranean fallow deer Dama dama and sub-tropical muntjac Muntiacus reevesi. Species-specific deer densities in buffers around culling locations of 492 adult female roe deer (sampled over seven years 2011-2017), were extracted from spatially-explicit Density Surface Models calibrated through extensive annual nocturnal thermal imaging distance sampling. Roe deer fertility and body mass were related to local species-specific deer 23 densities and local extent of arable lands (that provides nutritious food) using Piecewise Structural Equation Models. Muntjac density (mean=15.1 individuals.km-2 SD=7.6) was lower at higher fallow deer densities (inter-quartile effect size, IQ=-2.4 individuals.km-2), suggesting inter-specific avoidance (interference), but was greater when buffers included more arable (IQ=+1.01 individuals.km-2). Roe deer body mass (13.7kg, SD=1.52) was marginally greater when buffers included more arable (IQ=0.32kg) and was independent of deer densities. However, roe deer fertility was unrelated to body mass, suggesting fertility benefits of condition exceeded an asymptotic threshold in this low-density population. Consistent with this, roe deer fertility was slightly greater (not reduced) in areas with greater local roe deer density (IQ=+0.9% probability of two instead of one or zero embryos), again indicating negligible intra-specific competition. In contrast, roe deer were less fertile in areas with greater muntjac densities (IQ=-14%), thus inter-specific exceeded intra-specific competition in this assemblage. In contrast, we found no support for any effects of fallow deer density on roe deer density, body mass or fertility. Complex networks of inter-specific competition operate in this deer assemblage. For muntjac, interspecific interference from fallow deer exceeded habitat effects. For native roe deer, inter-specific competition from introduced, smaller sedentary muntjac reduced fertility, unlike intra-specific or potential competition with larger, more mobile, fallow deer. Mechanisms may include behavioural interference or stress; resource depletion is considered less likely as roe deer fertility was independent of body mass. Findings emphasise the importance of ensuring appropriate management strategies for controlling invasive species