Showing papers by "University of Greenland published in 2018"

Loss-of-function variants in ADCY3 increase risk of obesity and type 2 diabetes

Abstract: We have identified a variant in ADCY3 (encoding adenylate cyclase 3) associated with markedly increased risk of obesity and type 2 diabetes in the Greenlandic population. The variant disrupts a splice acceptor site, and carriers have decreased ADCY3 RNA expression. Additionally, we observe an enrichment of rare ADCY3 loss-of-function variants among individuals with type 2 diabetes in trans-ancestry cohorts. These findings provide new information on disease etiology relevant for future treatment strategies.

The evolutionary history of dogs in the Americas.

Abstract: Dogs were present in the Americas before the arrival of European colonists, but the origin and fate of these precontact dogs are largely unknown. We sequenced 71 mitochondrial and 7 nuclear genomes from ancient North American and Siberian dogs from time frames spanning ~9000 years. Our analysis indicates that American dogs were not derived from North American wolves. Instead, American dogs form a monophyletic lineage that likely originated in Siberia and dispersed into the Americas alongside people. After the arrival of Europeans, native American dogs almost completely disappeared, leaving a minimal genetic legacy in modern dog populations. The closest detectable extant lineage to precontact American dogs is the canine transmissible venereal tumor, a contagious cancer clone derived from an individual dog that lived up to 8000 years ago.

The population history of northeastern Siberia since the Pleistocene

Abstract: Far northeastern Siberia has been occupied by humans for more than 40 thousand years. Yet, owing to a scarcity of early archaeological sites and human remains, its population history and relationship to ancient and modern populations across Eurasia and the Americas are poorly understood. Here, we report 34 ancient genome sequences, including two from fragmented milk teeth found at the ~31.6 thousand-year-old (kya) Yana RHS site, the earliest and northernmost Pleistocene human remains found. These genomes reveal complex patterns of past population admixture and replacement events throughout northeastern Siberia, with evidence for at least three large-scale human migrations into the region. The first inhabitants, a previously unknown population of "Ancient North Siberians" (ANS), represented by Yana RHS, diverged ~38 kya from Western Eurasians, soon after the latter split from East Asians. Between 20 and 11 kya, the ANS population was largely replaced by peoples with ancestry from East Asia, giving rise to ancestral Native Americans and "Ancient Paleosiberians" (AP), represented by a 9.8 kya skeleton from Kolyma River. AP are closely related to the Siberian ancestors of Native Americans, and ancestral to contemporary communities such as Koryaks and Itelmen. Paleoclimatic modelling shows evidence for a refuge during the last glacial maximum (LGM) in southeastern Beringia, suggesting Beringia as a possible location for the admixture forming both ancestral Native Americans and AP. Between 11 and 4 kya, AP were in turn largely replaced by another group of peoples with ancestry from East Asia, the "Neosiberians" from which many contemporary Siberians derive. We detect additional gene flow events in both directions across the Bering Strait during this time, influencing the genetic composition of Inuit, as well as Na Dene-speaking Northern Native Americans, whose Siberian-related ancestry components is closely related to AP. Our analyses reveal that the population history of northeastern Siberia was highly dynamic, starting in the Late Pleistocene and continuing well into the Late Holocene. The pattern observed in northeastern Siberia, with earlier, once widespread populations being replaced by distinct peoples, seems to have taken place across northern Eurasia, as far west as Scandinavia.

Population genomics of grey wolves and wolf-like canids in North America.

Abstract: North America is currently home to a number of grey wolf (Canis lupus) and wolf-like canid populations, including the coyote (Canis latrans) and the taxonomically controversial red, Eastern timber and Great Lakes wolves. We explored their population structure and regional gene flow using a dataset of 40 full genome sequences that represent the extant diversity of North American wolves and wolf-like canid populations. This included 15 new genomes (13 North American grey wolves, 1 red wolf and 1 Eastern timber/Great Lakes wolf), ranging from 0.4 to 15x coverage. In addition to providing full genome support for the previously proposed coyote-wolf admixture origin for the taxonomically controversial red, Eastern timber and Great Lakes wolves, the discriminatory power offered by our dataset suggests all North American grey wolves, including the Mexican form, are monophyletic, and thus share a common ancestor to the exclusion of all other wolves. Furthermore, we identify three distinct populations in the high arctic, one being a previously unidentified “Polar wolf” population endemic to Ellesmere Island and Greenland. Genetic diversity analyses reveal particularly high inbreeding and low heterozygosity in these Polar wolves, consistent with long-term isolation from the other North American wolves.

Three lifestyle-related issues of major significance for public health among the Inuit in contemporary Greenland: a review of adverse childhood conditions, obesity, and smoking in a period of social transition.

Abstract: Greenland is a country in transition from a colonial past with subsistence hunting and fishing to an urban Nordic welfare state. Epidemiological transition from infectious to chronic diseases has been evident since the 1950s. Ninety percent of the population is Inuit. We studied three public health issues based on published literature, namely adverse childhood experiences, addictive behavior, and suicide; diet and obesity; and smoking. Alcohol consumption was high in the 1970s and 1980s with accompanying family and social disruption. This is still a cause of poor mental health and suicides in the generations most affected. The diet is changing from a traditional diet of fish and marine mammals to imported food including food items rich in sugar and fat from domestic animals, and the level of physical activity is decreasing with an ensuing epidemic rise in obesity. The prevalence of smoking is high at around 60% among both men and women and is only slowly decreasing. Smoking shows large social variation, and tobacco-related diseases are widespread. The diseases and conditions outlined above all contribute towards a low life expectancy at birth—69 years for men and 74 years for women in 2011–2015—compared with 78 and 84 years for men and women, respectively, on average in the European countries. The translation of government public health programs into local activities needs strengthening, and it must be realized that the improvement of public health is a long-term process.

Modern wolves trace their origin to a late Pleistocene expansion from Beringia

Abstract: Grey wolves (Canis lupus) are one of the few large terrestrial carnivores that maintained a wide geographic distribution across the Northern Hemisphere throughout the Pleistocene and Holocene Recent genetic studies have suggested that, despite this continuous presence, major demographic changes occurred in wolf populations between the late Pleistocene and early Holocene, and that extant wolves trace their ancestry to a single late Pleistocene population Both the geographic origin of this ancestral population and how it became widespread remain a mystery Here we analyzed a large dataset of novel modern and ancient mitochondrial wolf genomes, spanning the last 50,000 years, using a spatially and temporally explicit modeling framework to show that contemporary wolf populations across the globe trace their ancestry to an expansion from Beringia at the end of the Last Glacial Maximum - a process most likely driven by the significant ecological changes that occurred across the Northern Hemisphere during this period This study provides direct ancient genetic evidence that long-range migration has played an important role in the population history of a large carnivore and provides an insight into how wolves survived the wave of megafaunal extinctions at the end of the last glaciation Moreover, because late Pleistocene grey wolves were the likely source from which all modern dogs trace their origins, the demographic history described in this study has fundamental implications for understanding the geographical origin of the dog

Persistent organic pollutants and haematological markers in Greenlandic pregnant women: the ACCEPT sub-study

Abstract: The Arctic populations have high blood concentrations of persistent organic pollutants (POPs). Exposure to POPs was related to adverse health effects e.g. immune, neurological and reproductive systems. This study investigates associations between serum POP levels and haematological markers in Greenlandic pregnant women. This cross-sectional study included 189 women enrolled in 2010–2011 at the Greenlandic West coast by the inclusion criteria ≥18 years of age and had lived for 50% or more of their life in Greenland. The associations between the sum of the POP variables polychlorinated biphenyls (sumPCBs), organochlorine pesticides (sumOCPs), perfluoroalkylated substances (sumPFASs) and 24 haematological markers were analysed using linear regression adjusted for age, pre-pregnancy BMI, parity, gestation week, plasma-cotinine and alcohol intake. It showed a significantly inverse association between several haematological markers (eosinophil, lymphocyte, neutrophil and white blood cells) and sumPCBs, ...

Identification of novel high-impact recessively inherited type 2 diabetes risk variants in the Greenlandic population.

Abstract: In a recent study using a standard additive genetic model, we identified a TBC1D4 loss-of-function variant with a large recessive impact on risk of type 2 diabetes in Greenlanders. The aim of the current study was to identify additional genetic variation underlying type 2 diabetes using a recessive genetic model, thereby increasing the power to detect variants with recessive effects. We investigated three cohorts of Greenlanders (B99, n = 1401; IHIT, n = 3115; and BBH, n = 547), which were genotyped using Illumina MetaboChip. Of the 4674 genotyped individuals passing quality control, 4648 had phenotype data available, and type 2 diabetes association analyses were performed for 317 individuals with type 2 diabetes and 2631 participants with normal glucose tolerance. Statistical association analyses were performed using a linear mixed model. Using a recessive genetic model, we identified two novel loci associated with type 2 diabetes in Greenlanders, namely rs870992 in ITGA1 on chromosome 5 (OR 2.79, p = 1.8 × 10−8), and rs16993330 upstream of LARGE1 on chromosome 22 (OR 3.52, p = 1.3 × 10−7). The LARGE1 variant did not reach the conventional threshold for genome-wide significance (p < 5 × 10−8) but did withstand a study-wide Bonferroni-corrected significance threshold. Both variants were common in Greenlanders, with minor allele frequencies of 23% and 16%, respectively, and were estimated to have large recessive effects on risk of type 2 diabetes in Greenlanders, compared with additively inherited variants previously observed in European populations. We demonstrate the value of using a recessive genetic model in a historically small and isolated population to identify genetic risk variants. Our findings give new insights into the genetic architecture of type 2 diabetes, and further support the existence of high-effect genetic risk factors of potential clinical relevance, particularly in isolated populations. The Greenlandic MetaboChip-genotype data are available at European Genome-Phenome Archive (EGA; https://ega-archive.org/ ) under the accession EGAS00001002641.

Determinants of an integrated public health approach: the implementation process of Greenland’s second public health program

Abstract: Greenland struggles with a high prevalence of smoking, alcohol and drug abuse. In response to the increasing need for preventive initiatives, the first public health program Inuuneritta was introduced in 2007. Internationally, frameworks focus primarily on the implementation of a single, well-described intervention or program. However, with the increasing need and emergence of more holistic, integrated approaches, a need for research investigating the process of policy implementation from launch to action arises. This paper aims to augment the empirical evidence on the implementation of integrated health promotion programs within a governmental setting using the case of Inuuneritta II. In this study, the constraining and enabling determinants of the implementation processes within and across levels and sectors were examined. Qualitative methods with a transdisciplinary approach were applied. Data collection consisted of six phases with different qualitative methods applied to gain a comprehensive overview and understanding of Inuuneritta II’s implementation process. These methods included: observations and focus group discussions at the community health worker (CHW) conference, telephone interviews, document analysis, and a workshop on results dissemination. Enabling determinants influencing the implementation process of Inuuneritta II positively were high motivation among adopters, local prevention committees supporting community health workers, and the initiation of the central prevention committee. In contrast, constraining determinants were ambiguous program aims, high turnovers, siloed budgets and work environments, and an inconsistent and neglected central prevention committee. Inuuneritta II provided a substantial framework for an integrated health policy approach. However, having a holistic and comprehensive program enabling an integrated approach is not sufficient. Inuuneritta II’s integrated approach does not harmonise with the government’s inflexible organisational structure resulting in insufficient implementation.

Reproductive factors, lifestyle and dietary habits among pregnant women in Greenland: The ACCEPT sub-study 2013-2015.

Abstract: Background During past decades the formerly active lifestyle in Greenland has become sedentary, and the intake of traditional food has gradually been replaced with imported food. These lifestyle and dietary habits may affect pregnant women. Aim To describe age and regional differences in reproductive factors, lifestyle and diet among Greenlandic pregnant women in their first trimester. Methods A cross-sectional study during 2013-2015 including 373 pregnant women was conducted in five Greenlandic regions (West, Disko Bay, South, North and East). Interview-based questionnaires on reproductive factors, lifestyle and dietary habits were compared in relation to two age groups (median age ≤28 years and >28 years). Results In total, 72.4% were Inuit, 46.6% had BMI >25.0 kg/m2, 29.0% were smoking during pregnancy and 54.6% had used hashish. BMI, educational level, personal income, previous pregnancies and planned breastfeeding period were significantly higher in the age group >28 years of age compared to the age group ≤28 years of age. In region Disko Bay, 90.9% were Inuit, in region South more had a university degree (37.9%) and region East had the highest number of previous pregnancies, the highest number of smokers during pregnancy and the most frequent intake of sauce with hot meals and fast-food. Conclusions Overall a high BMI and a high smoking frequency were found. Age differences were found for BMI and planned breastfeeding period, while regional differences were found for smoking and intake of sauce with hot meals and fast-food. Future recommendations aimed at pregnant women in Greenland should focus on these health issues.

Genetic discovery and translational decision support from exome sequencing of 20,791 type 2 diabetes cases and 24,440 controls from five ancestries

Abstract: Protein-coding genetic variants that strongly affect disease risk can provide important clues into disease pathogenesis. Here we report an exome sequence analysis of 20,791 type 2 diabetes (T2D) cases and 24,440 controls from five ancestries. We identify rare (minor allele frequency 30 SLC30A8 alleles, and (b) within 12 gene sets, including those corresponding to T2D drug targets (p=6.1×10-3) and candidate genes from knockout mice (p=5.2×10-3). Within our study, the strongest T2D rare variant gene-level signals explain at most 25% of the heritability of the strongest common single variant signals, and the rare variant gene-level effect sizes we observe in established T2D drug targets will require 110K-180K sequenced cases to exceed exome-wide significance. To help prioritize genes using associations from current smaller sample sizes, we present a Bayesian framework to recalibrate association p-values as posterior probabilities of association, estimating that reaching p

Validation of cardiovascular diagnoses in the Greenlandic Hospital Discharge Register for epidemiological use.

Abstract: Cardiovascular disease (CVD) is one of the leading causes of death worldwide. In Greenland, valid estimates of prevalence and incidence of CVD do not exist and can only be calculated if diagnoses of CVD in the Greenlandic Hospital Discharge Register (GHDR) are correct. Diagnoses of CVD in GHDR have not previously been validated specifically. The objective of the study was to validate diagnoses of CVD in GHDR. The study was conducted as a validation study with primary investigator comparing information in GHDR with information in medical records. Diagnoses in GHDR were considered correct and thus valid if they matched the diagnoses or the medical information in the medical records. A total of 432 online accessible medical records with a cardiovascular diagnosis according to GHDR from Queen Ingrid's Hospital from 2001 to 2013 (n=291) and from local health care centres from 2007 to 2013 (n=141) were reviewed. Ninety-nine and ninety-two percent of discharge diagnosis in GHDR from Queen Ingrid's Hospital and local health care centres were correct in comparison with diagnoses in the medical record indicating valid registration practice. The correctness of cardiovascular diagnoses in GHDR was considered high in terms of acceptable agreement between medical records and diagnoses in GHDR. Cardiovascular diagnoses are valid for epidemiological use.

Measuring social inequality in health amongst indigenous peoples in the Arctic. A comparison of different indicators of social disparity among the Inuit in Greenland.

Abstract: The purpose of the article is to compare different indicators of social position as measures of social inequality in health in a population sample from an indigenous arctic people, the Inuit in Greenland. Data was collected during 2005-2015 and consisted of information from 3967 adult Inuit from towns and villages in all parts of Greenland. Social inequalities for smoking and central obesity were analysed in relation to seven indicators of social disparity in four dimensions, i.e. education and employment, economic status, sociocultural position, and place of residence. For each indicator we calculated age-adjusted prevalence by social group, rate ratio and the concentration index. The indicators were correlated with Pearson's r ranging from 0.24 to 0.82. Concentration indices ranged from 0.01 to 0.17. We could not conclude that one indicator was superior to others. Most of the indicators were traditional socioeconomic indicators used extensively in research in western countries and these seemed to be useful among the Inuit too, in particular household assets and job. Two sociocultural indicators developed for use among the Inuit and which included parameters specific to the indigenous peoples in the transition from a traditional to a modern life style proved to be equally useful but not superior to the traditional socioeconomic indicators. The choice of indicator must depend on what it is realistic to collect in the actual research setting and the use of more than one indicator is recommended. It is suggested to further develop culture specific indicators of social position for indigenous peoples.

Serum 25-hydroxyvitamin D, calcium and parathyroid hormone levels in Native and European populations in Greenland.

Abstract: Ca homoeostasis is important to human health and tightly controlled by powerful hormonal mechanisms that display ethnic variation. Ethnic variations could occur also in Arctic populations where the traditional Inuit diet is low in Ca and sun exposure is limited. We aimed to assess factors important to parathyroid hormone (PTH) and Ca in serum in Arctic populations. We included Inuit and Caucasians aged 50-69 years living in the capital city in West or in rural East Greenland. Lifestyle factors were assessed by questionnaires. The intake of Inuit diet was assessed from a FFQ. 25-Hydroxyvitamin D (25OHD2 and 25OHD3) levels were measured in serum as was albumin, Ca and PTH. The participation rate was 95 %, with 101 Caucasians and 434 Inuit. Median serum 25OHD (99·7 % was 25OHD3) in Caucasians/Inuit was 42/64 nmol/l (25, 75 percentiles 25, 54/51, 81) (P<0·001). Total Ca in serum was 2·33/2·29 mmol/l (25, 75 percentiles 2·26, 2·38/2·21, 2·36) (P=0·01) and PTH was 2·7/2·2 pmol/l (25, 75 percentiles 2·2, 4·1/1·7, 2·7) (P<0·001). The 69/97 Caucasians/Inuit with serum 25OHD <50 nmol/l differed in PTH (P=0·001) that rose with lower 25OHD levels in Caucasians, whereas this was not the case in Inuit. Ethnic origin influenced PTH (β=0·27, P<0·001) and Ca (β=0·22, P<0·001) in multivariate linear regression models after adjustment for age, sex, BMI, smoking, alcohol and diet. In conclusion, ethnic origin influenced PTH, PTH response to low vitamin D levels and Ca levels in populations in Greenland. Recommendations are to evaluate mechanisms underlying the ethnic influence on Ca homoeostasis and to assess the impact of transition in dietary habits on Ca homoeostasis and skeletal health in Arctic populations.

Greenland sled dogs at risk of extinction

Abstract: Dog ( Canis familiaris ) and sled remains found together suggest that the first sled dogs arose approximately 10,000 years ago ([ 1 ][1]). The ancestors to current sled dog breeds were essential to the Inuit's conquest of the Arctic. Sled dogs provided the main transport and hunting platform ([ 2 ][

Mexican Real Wages Before the Revolution: A Reappraisal

Abstract: Seminal literature has documented broadly the living conditions of Mexican workers before the Revolution of 1910 Various authors argue that a continuous deterioration of real wages in the preceding years of the Mexican revolution contributed to the social unrest that lead to the armed conflict Yet, most of the quantitative evidence has focused on aggregate estimates overlooking the regional wage dynamics Through regional historical data, this article reevaluates quantitatively the patterns of Mexican regional real wages providing new estimates for the period 1877-c1910 The analysis reveals that a divergent pattern between sectors and regions emerged during these years However, the study also shows that in general, locally-adjusted regional real wages remained relatively stable throughout the period

Genetic Variations, Exposure to Persistent Organic Pollutants and Breast Cancer Risk - A Greenlandic Case-Control Study.

Abstract: This study investigated the effects of single nucleotide polymorphisms (SNPs) in xenobiotic and steroid hormone-metabolizing genes in relation to breast cancer risk and explored possible effect modifications on persistent organic pollutants (POPs) and breast cancer associations. The study also assessed effects of Greenlandic BRCA1 founder mutations. Greenlandic Inuit women (77 cases and 84 controls) were included. We determined two founder mutations in BRCA1: Cys39Gly (rs80357164) and 4684delCC, and five SNPs in xenobiotic and oestrogen-metabolizing genes: CYP17A1 -34T>C (rs743572), CYP19A1 *19C>T (rs10046), CYP1A1 Ile462Val (rs1048943), CYP1B Leu432Val (rs1056836) and COMT Val158Met (rs4680). We used chi-square test for comparison of categorical variables between groups. Odds ratio (OR) estimates with 95% confidence interval (95%CI) were obtained using logistic regression models. The variant allele of BRCA1 Cys39Gly increased breast cancer risk (Gly/Cys versus Cys/Cys, OR: 12.2, 95%CI: 1.53; 98.1), and carriers of the variant allele of CYP17A1 -34T>C had reduced risk (CT+CC versus TT, OR: 0.44, 95%CI: 0.21; 0.93). CYP17A1 -34T>C was an effect modifier on the association between perfluoroalkyl acids (PFAAs) and breast cancer risk (∑PFAA, ratio of OR: 0.18, 95%CI: 0.03; 0.97). Non-significant modifying tendencies were seen for the other SNPs on the effect of polychlorinated biphenyls, organochlorine pesticides and PFAAs. In summary, the BRCA1 Cys39Gly and CYP17A1 -34T>C genetic variations were associated with breast cancer risk. Our results indicate that the evaluated genetic variants modify the effects of POP exposure on breast cancer risk; however, further studies are needed to document the data from the relatively small sample size.

Tuberculosis in the Circumpolar Region, 2006-2012.

Abstract: Setting The northern circumpolar jurisdictions Canada (Northwest Territories, Nunavik, Nunavut, Yukon), Finland, Greenland, Norway, Russian Federation (Arkhangelsk), Sweden and the United States (Alaska). Objective To describe and compare demographic, clinical and laboratory characteristics, including drug resistance and treatment completion, of tuberculosis (TB) cases in the northern circumpolar populations. Design Descriptive analysis of all active TB cases reported from 2006 to 2012 for incidence rate (IR), age and sex distribution, sputum smear and diagnostic site characteristics, drug resistance and treatment completion rates. Results The annual IR of TB disease ranged from a low of 4.3 per 100 000 population in Northern Sweden to a high of 199.5/100 000 in Nunavik, QC, Canada. For all jurisdictions, IR was higher for males than for females. Yukon had the highest proportion of new cases compared with retreatment cases (96.6%). Alaska reported the highest percentage of laboratory-confirmed cases (87.4%). Smear-positive pulmonary cases ranged from 25.8% to 65.2%. Multidrug-resistant cases ranged from 0% (Northern Canada) to 46.3% (Arkhangelsk). Treatment outcome data, available up to 2011, demonstrated >80% treatment completion for four of the 10 jurisdictions. Conclusion TB remains a serious public health issue in the circumpolar regions. Surveillance data contribute toward a better understanding and improved control of TB in the north.

Comparing health care workforce in circumpolar regions: patterns, trends and challenges.

Abstract: Background: The eight Arctic States exhibit substantial health disparities between their remote northernmost regions and the rest of the country. This study reports on the trends and patterns in th...

Prevalence of antibodies against Brucella spp. in West Greenland polar bears ( Ursus maritimus ) and East Greenland muskoxen ( Ovibos moschatus )

Abstract: Zoonotic infections transmitted from terrestrial and marine mammals to humans in European Arctic are of unknown significance, despite considerable potential for transmission due to local hunt and a rapidly changing environment. As an example, infection with Brucella bacteria may have significant impact on human health due to consumption of raw meat or otherwise contact with tissues and fluids of infected game species such as muskoxen and polar bears. Here, we present serological results for Baffin Bay polar bears (Ursus maritimus) (n = 96) and North East Greenland muskoxen (Ovibos moschatus) (n = 32) for antibodies against Brucella spp. The analysis was a two-step trial initially using the Rose Bengal Test (RBT), followed by confirmative competitive enzyme-linked immunosorbent assays of RBT-positive samples. No muskoxen had antibodies against Brucella spp., while antibodies were detected in six polar bears (6.25%) rendering a seroprevalence in line with previous findings in other Arctic regions. Seropositivity was not related to sex, age or biometrics i.e. size and body condition. Whether Brucella spp. antibodies found in polar bears were due to either prey spill over or true recurrent Brucella spp. infections is unknown. Our results therefore highlight the importance of further research into the zoonotic aspects of Brucella spp. infections, and the impact on wildlife and human health in the Arctic region.

Genetic determinants of glycated hemoglobin levels in the Greenlandic Inuit population

Abstract: We previously showed that a common genetic variant leads to a remarkably increased risk of type 2 diabetes (T2D) in the small and historically isolated Greenlandic population. Motivated by this, we aimed at discovering novel genetic determinants for glycated hemoglobin (HbA1C) and at estimating the effect of known HbA1C-associated loci in the Greenlandic population. We analyzed genotype data from 4049 Greenlanders generated using the Illumina Cardio-Metabochip. We performed the discovery association analysis by an additive linear mixed model. To estimate the effect of known HbA1C-associated loci, we modeled the effect in the European and Inuit ancestry proportions of the Greenlandic genome (EAPGG and IAPGG, respectively). After correcting for multiple testing, we found no novel significant associations. When we investigated loci known to associate with HbA1C levels, we found that the lead variant in the GCK locus associated significantly with HbA1C levels in the IAPGG ( $$P_{IAPGG} = 4.8 \times 10^{ - 6},\,\beta _{IAPGG} = 0.13\,{\mathrm{SD}}$$ ). Furthermore, for 10 of 15 known HbA1C loci, the effects in IAPGG were similar to the previously reported effects. Interestingly, the ANK1 locus showed a statistically significant ancestral population differential effect, with opposing directions of effect in the two ancestral populations. In conclusion, we found only 1 of the 15 known HbA1C loci to be significantly associated with HbA1C levels in the IAPGG and that two-thirds of the loci showed similar effects in Inuit as previously found in European and East Asian populations. Our results shed light on the genetic effects across ethnicities.

Patient Participation in Healthcare Practice in Greenland: Local Challenges and Global Reflections

Abstract: Various kinds of user and patient involvement are spreading in healthcare in most Western countries. The purpose of this study is to critically assess the actual conditions for patients’ involvement in healthcare practice in Greenland and to point to possibilities for development. Patients’ perspectives on their own conduct of everyday life with illness and their possibilities for participation when hospitalized are examined in relation to the conditions in a hospital setting dominated by biomedical practice. On a theoretical level, it is argued that the concept of ‘participation’ is preferable to the concept ‘involvement’ in healthcare. The study shows that there are several interconnected areas for development: the structural frames of hospital practice, including professionals’ possibilities for handling patient participation, and the agency of the patients conducting their everyday lives when hospitalized. Consequences of the biomedical hegemony are discussed in relation to WHO s broader approach to disease, illness and health and the still existing postcolonial traces of power and hierarchy. Finally it is argued that patient participation during hospitalization will promote the patients conduct of everyday life, the cultural knowledge of the professionals, and the democratization of the healthcare sector. Such changes might be connected to a more encompassing democratic societal development – in Greenland as well as globally.

Summary of available surveillance data on hepatitis C virus infection from eight Arctic countries, 2012 to 2014

Abstract: We summarised available hepatitis C virus (HCV) surveillance data for 2012-14 from Arctic/sub-Arctic countries/regions. We sent a HCV data collection template by email to public health authorities in all jurisdictions. Population statistics obtained from census sources for each country were used to estimate rates of reported acute and chronic/undifferentiated HCV cases. Seven countries with Arctic regions (Canada, Denmark, Finland, Greenland, Norway, Sweden and the United States, represented by the state of Alaska), including three Canadian territories and one province, as well as 11 Russian subnational Arctic regions, completed the data collection template. Data on acute HCV infection during 2014 was available from three Arctic countries and all Russian Arctic regions (rate range 0/100,000 population in Greenland, as well as Nenets and Chukotka Automous Okrugs (Russian subnational Arctic regions) to 3.7/100,000 in the Russian Republic of Komi). The rate of people with chronic/undifferentiated HCV infection in 2014 ranged from 0/100,000 in Greenland to 171.2/100,000 in Alaska. In most countries/regions, the majority of HCV-infected people were male and aged 19-64 years. Differences in surveillance methods preclude direct comparisons of HCV surveillance data between Arctic countries/regions. Our data can inform future efforts to develop standardised approaches to HCV surveillance in the Arctic countries/regions by identifying similarities/differences between the surveillance data collected.

Development of health‐related quality of life and symptoms in patients with advanced cancer in Greenland

Abstract: A prospective national cohort study assessed the development of health-related quality of life (HRQoL) and symptoms in adult patients undergoing treatment and care for advanced cancer in Greenland. HRQol was examined by EORTC QLQ-C30 version 3.0 questionnaire monthly for 4 months. Changes over time and between-group comparisons were examined. Of 58 patients included in the study, 47% completed the questionnaire four times. Functioning was generally high, and improved social functioning was observed after 1 and 2 months. The highest symptom score was for fatigue followed by pain and nausea/vomiting. A high score for financial problems remained unchanged during the entire period. Patients with higher income had reduced pain intensity (p = .03) and diarrhoea (p = .05) than patients with income below the poverty line. After 1 month, reduction in pain intensity was observed for Nuuk citizens compared with non-Nuuk citizens (p = .05). After 2 months, non-Nuuk citizens reported improved social functioning compared with Nuuk citizens (p = .05). After 3 months, Global Health in Nuuk citizens was improved compared with non-Nuuk citizens (p = .05). An important clinical finding was that patients' needs for support are related to social status, and geographical factors should be taken into account when planning palliative care.

Study of correlation between the NAT2 phenotype and genotype status among Greenlandic Inuit.

Abstract: N-acetyltransferase 2 (NAT2) is the main enzyme metabolizing isoniazid and genotype-based treatment has been studied for years without becoming common practice. To investigate whether genotype-based isoniazid treatment is feasible in Greenland, we sequenced the coding sequence of NAT2 and determined the NAT2 enzyme-activity by caffeine test. No additional genetic variants were identified in the coding sequence of NAT2, so that genotype status in 260 study participants could be assessed by a well-established 7-SNP panel. Studying the enzyme activity by the ratio of the two caffeine metabolites AFMU and 1X in 260 participants showed a high rate of slow phenotypes with intermediate or rapid genotype. These misclassifications were mainly observed in urine samples with pH 3, we observed a moderate level of discrepancies (19 of the 116 individuals with intermediate or rapid genotype status having a slow phenotype). Further investigation showed that drinking coffee and not tea or cola was the most important factor for high levels of both metabolites. The concordance between phenotype and genotype status with regard to slow metabolism supported the recommendation of lower isoniazid doses in individuals with slow genotype status in order to avoid liver injury, a frequent side effect. The phenotypical variation observed for individuals with intermediate or rapid genotype status warrants further research before increased dosing of isoniazid can be recommended.