Diving below the surface: A framework for arctic health research to support thriving communities.

AIMS: Historically, health research in the Arctic has focused on documenting ill-health using a narrow set of deficit-oriented epidemiologic indicators (i.e., prevalence of disease and mortality rates). While useful, this type of research does not adequately capture the breadth and complexities of community health and well-being, and fails to highlight solutions. A community's context, strengths, and continued expressions of well-being need to guide inquiries, inform processes, and contextualize recommendations. In this paper, we present a conceptual framework developed to address the aforementioned concerns and inform community-led health and social research in the Arctic. METHODS: The proposed framework is informed by our collective collaborations with circumpolar communities, and syntheses of individual and group research undertaken throughout the Circumpolar North. Our framework encourages investigation into the contextual factors that promote circumpolar communities to thrive. RESULTS: Our framework centers on the visual imagery of an iceberg. There is a need to dive deeper than superficial indicators of health to examine individual, family, social, cultural, historical, linguistic, and environmental contexts that support communities in the Circumpolar North to thrive. A participatory community-based approach in conjunction with ongoing epidemiologic research is necessary in order to effectively support health and wellness. Conclusions: The iceberg framework is a way to conceptualize circumpolar health research and encourage investigators to both monitor epidemiologic indicators and also dive below the surface using participatory methodology to investigate contextual factors that support thriving communities.

An LDLR missense variant poses high risk of familial hypercholesterolemia in 30% of Greenlanders and offers potential of early cardiovascular disease intervention.

The common Arctic-specific LDLR p.G137S variant was recently shown to be associated with elevated lipid levels. Motivated by this, we aimed to investigate the effect of p.G137S on metabolic health and cardiovascular disease risk among Greenlanders to quantify its impact on the population. In a population-based Greenlandic cohort (n = 5,063), we tested for associations between the p.G137S variant and metabolic health traits as well as cardiovascular disease risk based on registry data. In addition, we explored the variant's impact on plasma NMR measured lipoprotein concentration and composition in another Greenlandic cohort (n = 1,629); 29.5% of the individuals in the cohort carried at least one copy of the p.G137S risk allele. Furthermore, 25.4% of the heterozygous and 54.7% of the homozygous carriers had high levels (>4.9 mmol/L) of serum LDL cholesterol, which is above the diagnostic level for familial hypercholesterolemia (FH). Moreover, p.G137S was associated with an overall atherosclerotic lipid profile, and increased risk of ischemic heart disease (HR [95% CI], 1.51 [1.18-1.92], p = 0.00096), peripheral artery disease (1.69 [1.01-2.82], p = 0.046), and coronary operations (1.78 [1.21-2.62], p = 0.0035). Due to its high frequency and large effect sizes, p.G137S has a marked population-level impact, increasing the risk of FH and cardiovascular disease for up to 30% of the Greenlandic population. Thus, p.G137S is a potential marker for early intervention in Arctic populations.

Prevalence and Trends in Problem Gambling in Denmark with Special Focus on Country of Origin: Results from the Danish Health and Morbidity Surveys.

Belonging to an ethnic minority has been described as a possible risk factor for problem gambling, but the literature is inconclusive whether this association is true or just a proxy for other underlying risk factors. Hence, the aims were to investigate: (1) past year prevalence of problem gambling in the adult Danish population and trends since 2005, (2) past year prevalence of problem gambling in 2017 and trends since 2010 by country of origin, and (3) whether a marginalisation by country of origin or problem gambling, respectively, is seen in various health-related indicators. Data were derived from the Danish Health and Morbidity Surveys in 2005, 2010, 2013, and 2017. The Lie/Bet Questionnaire was used to define problem gamblers. The overall prevalence of past year problem gambling has increased slightly from 2005 (1.0%) to 2017 (1.5%), but a more alarming increase was observed among men with non-western origin (3.1% in 2010 and 7.0% in 2017). A lower prevalence of good self-rated health and a higher prevalence of poor mental health was observed among individuals with a non-western origin compared to those with a Danish origin, although the differences became smaller between 2010 and 2017. The findings indicate a slightly increase in the prevalence of past year problem gambling and that particular attention should be paid to individuals with a non-western origin. The study also highlights the need for better differentiation of risk factors that may variously predispose different ethnic groups to develop gambling problems.

Loss of Sucrase-Isomaltase Function Increases Acetate Levels and Improves Metabolic Health in Greenlandic Cohorts.

BACKGROUND & AIMS: The sucrase-isomaltase (SI) c.273_274delAG loss-of-function variant is common in Arctic populations and causes congenital sucrase-isomaltase deficiency, which is an inability to break down and absorb sucrose and isomaltose. Children with this condition experience gastrointestinal symptoms when dietary sucrose is introduced. We aimed to describe the health of adults with sucrase-isomaltase deficiency. METHODS: The association between c.273_274delAG and phenotypes related to metabolic health was assessed in 2 cohorts of Greenlandic adults (n = 4922 and n = 1629). A sucrase-isomaltase knockout (Sis-KO) mouse model was used to further elucidate the findings. RESULTS: Homozygous carriers of the variant had a markedly healthier metabolic profile than the remaining population, including lower body mass index (ß [standard error], -2.0 [0.5] kg/m2; P = 3.1 × 10-5), body weight (-4.8 [1.4] kg; P = 5.1 × 10-4), fat percentage (-3.3% [1.0%]; P = 3.7 × 10-4), fasting triglyceride (-0.27 [0.07] mmol/L; P = 2.3 × 10-6), and remnant cholesterol (-0.11 [0.03] mmol/L; P = 4.2 × 10-5). Further analyses suggested that this was likely mediated partly by higher circulating levels of acetate observed in homozygous carriers (ß [standard error], 0.056 [0.002] mmol/L; P = 2.1 × 10-26), and partly by reduced sucrose uptake, but not lower caloric intake. These findings were verified in Sis-KO mice, which, compared with wild-type mice, were leaner on a sucrose-containing diet, despite similar caloric intake, had significantly higher plasma acetate levels in response to a sucrose gavage, and had lower plasma glucose level in response to a sucrose-tolerance test. CONCLUSIONS: These results suggest that sucrase-isomaltase constitutes a promising drug target for improvement of metabolic health, and that the health benefits are mediated by reduced dietary sucrose uptake and possibly also by higher levels of circulating acetate.

The genetic history of Greenlandic-European contact.

The Inuit ancestors of the Greenlandic people arrived in Greenland close to 1,000 years ago.1 Since then, Europeans from many different countries have been present in Greenland. Consequently, the present-day Greenlandic population has ∼25% of its genetic ancestry from Europe.2 In this study, we investigated to what extent different European countries have contributed to this genetic ancestry. We combined dense SNP chip data from 3,972 Greenlanders and 8,275 Europeans from 14 countries and inferred the ancestry contribution from each of these 14 countries using haplotype-based methods. Due to the rapid increase in population size in Greenland over the past ∼100 years, we hypothesized that earlier European interactions, such as pre-colonial Dutch whalers and early German and Danish-Norwegian missionaries, as well as the later Danish colonists and post-colonial immigrants, all contributed European genetic ancestry. However, we found that the European ancestry is almost entirely Danish and that a substantial fraction is from admixture that took place within the last few generations.

The effect of household crowding and composition on health in an Inuit cohort in Greenland.

Aims: This study aims to investigate the association between household crowding and household composition and self-rated health and mental health (GHQ scale) among the Inuit in Greenland. Poor housing conditions are a concern in Greenland, especially in the villages, where socioeconomic standards in general are lower. Methods: A cohort of 1282 adults participated in two population-based surveys in Greenland, the Inuit Health in Transition survey 2005-2010 (baseline) and The Health Survey in Greenland 2014 (follow-up). Associations between household conditions at baseline and health outcomes at follow-up (poor self-rated health and mental health measured by the GHQ scale) were examined using logistic regression models, adjusting for covariates at baseline. Results: Participants living in an overcrowded dwelling (more than one person per room) at baseline were more likely to report poor self-rated health at follow-up (OR 1.47; 95% CI 1.09; 1.99) compared with those not living in an overcrowded dwelling. In addition, participants who lived alone at baseline were more likely (OR 1.98; 95% CI 1.09; 3.58) to experience poor mental health at follow-up compared with those who lived with children. Conclusions: Results indicate that household conditions are related to health in Greenland. Public health authorities should work to ensure affordable housing of good quality in all communities.

Alcohol in Greenland 1950-2018: consumption, drinking patterns, and consequences.

Alcohol is the single most important public health challenge in Greenland. We provide an overview of alcohol consumption, drinking patterns, and consequences of excessive use of alcohol in Greenland since 1950 through a synthesis of published results and analyses of population-based interview surveys. The import of alcohol fluctuated over the last 70 years with a peak in the 1980s at 22 litres 100% alcohol per person per year. In 1950 and 2015, the import of alcohol was similar at 8 litres. Several explanations have been put forward to explain the changes including restrictions, increased tax, demographic changes, treatment of alcohol disorders, and public health interventions. The proportion of abstainers increased from 1993 to 2018 while the proportion of participants with regular consumption decreased. About half of the population reported binge drinking at least monthly. Compared with Denmark, there were more abstainers and binge drinkers in Greenland, and fewer had a regular consumption. Although genetics may play a role for drinking patterns, social and cultural conditions are more important. Exposure to domestic alcohol problems and sexual abuse in childhood parallel the recorded import of alcohol and is a likely cause of transgenerational consequences such as youth suicides and alcohol problems.

The derived allele of a novel intergenic variant at chromosome 11 associates with lower body mass index and a favorable metabolic phenotype in Greenlanders.

The genetic architecture of the small and isolated Greenlandic population is advantageous for identification of novel genetic variants associated with cardio-metabolic traits. We aimed to identify genetic loci associated with body mass index (BMI), to expand the knowledge of the genetic and biological mechanisms underlying obesity. Stage 1 BMI-association analyses were performed in 4,626 Greenlanders. Stage 2 replication and meta-analysis were performed in additional cohorts comprising 1,058 Yup'ik Alaska Native people, and 1,529 Greenlanders. Obesity-related traits were assessed in the stage 1 study population. We identified a common variant on chromosome 11, rs4936356, where the derived G-allele had a frequency of 24% in the stage 1 study population. The derived allele was genome-wide significantly associated with lower BMI (beta (SE), -0.14 SD (0.03), p = 3.2x10-8), corresponding to 0.64 kg/m2 lower BMI per G allele in the stage 1 study population. We observed a similar effect in the Yup'ik cohort (-0.09 SD, p = 0.038), and a non-significant effect in the same direction in the independent Greenlandic stage 2 cohort (-0.03 SD, p = 0.514). The association remained genome-wide significant in meta-analysis of the Arctic cohorts (-0.10 SD (0.02), p = 4.7x10-8). Moreover, the variant was associated with a leaner body type (weight, -1.68 (0.37) kg; waist circumference, -1.52 (0.33) cm; hip circumference, -0.85 (0.24) cm; lean mass, -0.84 (0.19) kg; fat mass and percent, -1.66 (0.33) kg and -1.39 (0.27) %; visceral adipose tissue, -0.30 (0.07) cm; subcutaneous adipose tissue, -0.16 (0.05) cm, all p<0.0002), lower insulin resistance (HOMA-IR, -0.12 (0.04), p = 0.00021), and favorable lipid levels (triglyceride, -0.05 (0.02) mmol/l, p = 0.025; HDL-cholesterol, 0.04 (0.01) mmol/l, p = 0.0015). In conclusion, we identified a novel variant, where the derived G-allele possibly associated with lower BMI in Arctic populations, and as a consequence also leaner body type, lower insulin resistance, and a favorable lipid profile.

Symposium on "parental education" at the ICCH17.

This symposium report provides a brief overview of the six programmes and studies on parental education and maternal health services within the circumpolar region presented in the symposium "parental education" at the 17th International Congress of Circumpolar Health in Copenhagen, Denmark, August 2018.

RISING SUN: Prioritized Outcomes for Suicide Prevention in the Arctic.

The Arctic Council, a collaborative forum among governments and Arctic communities, has highlighted the problem of suicide and potential solutions. The mental health initiative during the United States chairmanship, Reducing the Incidence of Suicide in Indigenous Groups: Strengths United Through Networks (RISING SUN), used a Delphi methodology complemented by face-to-face stakeholder discussions to identify outcomes to evaluate suicide prevention interventions. RISING SUN underscored that multilevel suicide prevention initiatives require mobilizing resources and enacting policies that promote the capacity for wellness, for example, by reducing adverse childhood experiences, increasing social equity, and mitigating the effects of colonization and poverty.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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

AIMS/HYPOTHESIS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS/INTERPRETATION: 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. DATA AVAILABILITY: The Greenlandic MetaboChip-genotype data are available at European Genome-Phenome Archive (EGA; https://ega-archive.org/ ) under the accession EGAS00001002641.

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.

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.

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

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.

Associations between vitamin D status and atherosclerosis among Inuit in Greenland.

BACKGROUND AND AIMS: Low levels of vitamin D are suspected to be a risk factor for cardiovascular disease and atherosclerosis. The aim of this study was to assess the prevalence of subclinical atherosclerosis among Inuit in Greenland, and to evaluate the association with vitamin D status. We hypothesized that low vitamin D status could be associated with higher carotid intima-media thickness (IMT) as a marker of atherosclerosis. METHODS: 756 adults from the Inuit Health in Transition (IHIT) study carried out in Greenland in the period 2005-2010 were included. A blood sample donated in 1987 was available for a sub-sample of 102 individuals. Serum 25(OH)D3 from the IHIT study and the 1987 survey was used as a measure of vitamin D status. IMT measurements were conducted by ultrasound scanning. The prevalence of atherosclerosis was estimated, and the association between serum 25(OH)D3 and IMT measurements was examined by linear regression. RESULTS: The overall prevalence of subclinical atherosclerosis was 20.1% (n = 152). The linear regression analyses indicated a weak positive association between serum 25(OH)D3 level and IMT measurements from the IHIT study, though not statistically significant after adjustment for potential confounders (ß = 0.35% per 10 nmoL/L 25(OH)D3, p = 0.06). Linear regression analyses of the association between serum 25(OH)D3 level in the 1987 survey and IMT measurements also indicated a positive, though not statistically significant, association after adjustment (ß = 0.07% per 10 nmoL/L 25(OH)D3, p = 0.86). CONCLUSIONS: Our findings did not support the hypothesis of an association between low vitamin D levels and risk of atherosclerosis.

Stable isotopes of carbon and nitrogen as markers of dietary variation among sociocultural subgroups of Inuit in Greenland.

OBJECTIVES: We assessed the use of stable isotopes of carbon and nitrogen as biomarkers for traditional versus store-bought food among the Inuit. Furthermore, we compared the isotope patterns among sociocultural population groups. METHODS: As a part of a country-wide health survey in Greenland during 2005-2010, we analyzed the isotope composition of toenails from 1025 adult Inuit and meat of common species hunted for food. Information on diet and sociocultural variables was collected by interviews. RESULTS: Weighted by sex and place of residence to the total population of Inuit in Greenland, the average δ13 C value in toenails was -20.2‰ and the δ15 N value was 12.0‰ which are higher than in a general Danish omnivorous population. Both isotopes were significantly associated with other biomarkers of marine food and with results of a Food Frequency Questionnaire (FFQ). The percentage of marine food in the diet was estimated at 21% from the mean δ13 C value, 25% from the mean δ15 N value, and 23% from the FFQ. CONCLUSION: Nail samples for analysis of stable isotopes of carbon and nitrogen were convenient to collect during a large population health survey among the Inuit. Isotope enrichment levels showed statistically significant associations with other biomarkers for consumption of marine food and with results of an FFQ and were used to estimate the percentage of marine food in the diet. Isotope levels were significantly associated with a novel score of sociocultural transition.

Health behaviour and body mass index among problem gamblers: results from a nationwide survey.

Problem gambling is a serious public health issue. The objective of this study was to investigate whether past year problem gamblers differed from non-problem gamblers with regard to health behaviour and body mass index (BMI) among Danes aged 16 years or older. Data were derived from the Danish Health and Morbidity Surveys in 2005 and 2010. Past year problem gambling was defined using the lie/bet questionnaire. Logistic regression analyses were used to examine the association between past year problem gambling and health behaviour and BMI. Problem gambling was associated with unhealthy behaviour and obesity. The odds of smoking was significantly higher among problem gamblers than among non-problem gamblers. Further, the odds of high-risk alcohol drinking and illicit drug use were significantly higher among problem gamblers. The prevalence of sedentary leisure activity, unhealthy diet pattern and obesity was higher among problem gamblers than among non-problem gamblers. The associations found in this study remained significant after adjustment for sex, age, educational and cohabiting status as well as other risk factors. Our findings highlight the presence of a potential, public health challenge and elucidate the need for health promotion initiatives targeted at problem gamblers. Furthermore, more research is needed in order to understand the underlying social mechanism of the association between problem gamblers and unhealthy behaviour.

The prevalence of problem gambling in Denmark in 2005 and 2010: a sociodemographic and socioeconomic characterization.

Gambling is a worldwide phenomenon. For most persons this causes only small or no problems, but for some, pathological gambling can be the result of entering the gambling environment. The objectives were to estimate the past year and lifetime prevalence of problem gambling in the adult Danish population (16 years or older) in 2010 and trends since 2005 and, furthermore, to investigate whether problem gamblers differed from non-problem gamblers with regard to sociodemographic and socioeconomic factors. Data were derived from two national representative Danish health surveys. The survey in 2005 was based on region-stratified random sample of 10,916 Danish citizens (response rate: 52.1 %) and the survey in 2010 was based on a random sample of 23,405 Danish citizens (response rate: 62.7 %). Problem gambling was defined using the lie/bet questionnaire. The past year prevalence of problem gamblers in Denmark remained stable from 2005 to 2010 (0.9 and 0.8 %, respectively). The highest past year prevalence of problem gamblers was found among young men in both 2005 and 2010. Furthermore, problem gamblers were more prevalent among men, disability pensioners, less educated and those not married or cohabiting. The present study indicates that a high level of education and being employed have a protective effect against problem gambling. More research is needed in order to understand what attracts and maintains the interest of men in gambling environments as well as why women are not occupied by gambling in the same degree as men.