Palaeo-Eskimo genetic ancestry and the peopling of Chukotka and North America.

Much of the American Arctic was first settled 5,000 years ago, by groups of people known as Palaeo-Eskimos. They were subsequently joined and largely displaced around 1,000 years ago by ancestors of the present-day Inuit and Yup'ik1-3. The genetic relationship between Palaeo-Eskimos and Native American, Inuit, Yup'ik and Aleut populations remains uncertain4-6. Here we present genomic data for 48 ancient individuals from Chukotka, East Siberia, the Aleutian Islands, Alaska, and the Canadian Arctic. We co-analyse these data with data from present-day Alaskan Iñupiat and West Siberian populations and published genomes. Using methods based on rare-allele and haplotype sharing, as well as established techniques4,7-9, we show that Palaeo-Eskimo-related ancestry is ubiquitous among people who speak Na-Dene and Eskimo-Aleut languages. We develop a comprehensive model for the Holocene peopling events of Chukotka and North America, and show that Na-Dene-speaking peoples, people of the Aleutian Islands, and Yup'ik and Inuit across the Arctic region all share ancestry from a single Palaeo-Eskimo-related Siberian source.

Wild fish consumption and latitude as drivers of vitamin D status among Inuit living in Nunavik, northern Québec.

OBJECTIVE: To measure vitamin D status and estimate factors associated with serum 25-hydroxyvitamin D (25(OH)D) in Nunavimmiut (Inuit living in Nunavik) adults in 2017. DESIGN: Data were from Qanuilirpitaa? 2017 Nunavik Inuit Health Survey, a cross-sectional study conducted in August-October 2017. Participants underwent a questionnaire, including an FFQ, and blood samples were analysed for total serum 25(OH)D. SETTING: Nunavik, northern Québec, Canada. PARTICIPANTS: A stratified proportional model was used to select respondents, including 1,155 who identified as Inuit and had complete data. RESULTS: Geometric mean serum vitamin D levels were 65·2 nmol/l (95 % CI 62·9-67·6 nmol/l) among women and 65·4 nmol/l (95 % CI 62·3-68·7 nmol/l) among men. The weighted prevalence of serum 25(OH)D < 75 nmol/l, <50 nmol/l <30 nmol/l was 61·2 %, 30·3 % and 7·0 %, respectively. Individuals who were older, female, lived in smaller and/or more southerly communities and/or consumed more country (traditional) foods were at a reduced risk of low vitamin D status. Higher consumption of wild fish was specifically associated with increased serum 25(OH)D concentration. CONCLUSION: It is important that national, regional and local policies and programs are in place to secure harvest, sharing and consumption of nutritious and culturally important country foods like Arctic char and other wild fish species, particularly considering ongoing climate change in the Arctic which impacts the availability, access and quality of fish as food.

Malignancy rates of salivary gland tumors in Greenlandic Inuit comparable to non-endemic populations; epidemiological mapping of salivary gland tumors 1990-2019.

BACKGROUND: Salivary gland tumors are assumed to be predominantly malignant in the Greenlandic Inuit population, but there is limited literature on the subject. We conducted a retrospective cohort study using national registers to describe the histological tumor types, location, incidence, and survival of benign and malignant salivary gland tumors. METHODS: We analyzed data on all Greenlandic Inuit with an epithelial-derived salivary gland tumor from 1990 to 2019. We extracted data from the Central Personal Registry and crossmatched it with the Danish Pathology Data Bank. All specimens were reviewed by a specialized pathologist. We noted patient and histological characteristics, calculated crude and age-adjusted incidence rates, overall survival, and excess mortality. RESULTS: Our study found that 76% of salivary gland tumors in the Greenlandic Inuit population were benign, with pleomorphic adenoma being the most common. Malignant tumors accounted for 24% of cases, with lymphoepithelial carcinoma being the most common type. The most common place of origin for malignant tumors was the parotid gland (71%) and the submandibular gland (15%). The median age of onset for malignant tumors was 47 years. Age-adjusted incidence rates of malignant tumors for men and women were 3.00 and 4.12 per 100,000 person-years, respectively. CONCLUSION: Our findings suggest that the proportion of malignant salivary gland tumors in the Greenlandic Inuit population is similar to other nonendemic populations. Our incidence rates are higher than previously reported, likely due to differences in methodology and definitions of the Inuit population. This study provides valuable insights into the epidemiology of salivary gland tumors in the Greenlandic Inuit population and may have implications for other Inuit populations as well.

Time trends and geographical patterns in suicide among Greenland Inuit.

BACKGROUND: Between 1980 and 2018 Greenland has had one of the highest suicide rates in the world with an average rate of 96 suicides per 100,000 people annually. The aim of this study is to investigate suicide rates in Greenland according to age, birth cohort, period, sex, place of residence and suicide method from 1970 until 2018. METHODS: Suicide rates were examined using register and census data from 1970-2018 among Greenland Inuit. Rates were calculated by Poisson regression in Stata and by use of Excel. In analyses of the period trends, rates were standardized according to the World Standard Population 2000-2025. RESULTS: The suicide rate has been declining since a peak at 120 suicides per 100,000 people annually in the 1980s but remained high at a rate of 81.3 suicides per 100,000 people annually from 2015-2018. Descriptive analyses point to the decrease in male suicides as the primary factor for the overall decreasing rates while the rate among women has been increasing. Simultaneously, the proportion of women who used a violent suicide method increased from 60% in 1970-1979 to 90% in 2010-2018. The highest rates are seen among young people, especially young men aged 20-24 years and youth suicide rates increased with later birth cohorts. When the rates started to increase in the 1980s both the capital Nuuk and East Greenland had the highest rates. Since then, the rate in Nuuk has declined while the rate in East Greenland was three times the national rate from 2015-2018. CONCLUSIONS: From 1970 to 1989 the suicide rate increased from 28.7 to 120.5 per 100,000 people mirroring a rapid societal transition in the post-colonial period. The rate has slowly declined from the peak in the 1980s but remains at a very high level. Young people in general are at risk, but the steady increase in the rate among women is worrying and there is a need to investigate underlying causes for this development.

Giving birth in a good way when it must take place away from home: Participatory research into visions of Inuit families and their Montreal-based medical providers.

BACKGROUND: Transferring pregnant women out of their communities for childbirth continues to affect Inuit women living in Nunavik-Inuit territory in Northern Quebec. With estimates of maternal evacuation rates in the region between 14% and 33%, we examine how to support culturally safe birth for Inuit families when birth must take place away from home. METHODS: A participatory research approach explored perceptions of Inuit families and their perinatal healthcare providers in Montreal for culturally safe birth, or "birth in a good way" in the context of evacuation, using fuzzy cognitive mapping. We used thematic analysis, fuzzy transitive closure, and an application of Harris' discourse analysis to analyze the maps and synthesize the findings into policy and practice recommendations. RESULTS: Eighteen maps authored by 8 Inuit and 24 service providers in Montreal generated 17 recommendations related to culturally safe birth in the context of evacuation. Family presence, financial assistance, patient and family engagement, and staff training featured prominently in participant visions. Participants also highlighted the need for culturally adapted services, with provision of traditional foods and the presence of Inuit perinatal care providers. Stakeholder engagement in the research resulted in dissemination of the findings to Inuit national organizations and implementation of several immediate improvements in the cultural safety of flyout births to Montreal. CONCLUSIONS: The findings point toward the need for culturally adapted, family-centered, and Inuit-led services to support birth that is as culturally safe as possible when evacuation is indicated. Application of these recommendations has the potential to benefit Inuit maternal, infant, and family wellness.

Exploring community perspectives on the impacts of COVID-19 on food security and food sovereignty in Nunavut communities.

BACKGROUND: In Nunavut, where 70% of children are food insecure, many households rely on school breakfast or community food programmes for nourishment. The COVID-19 pandemic and resulting policies to reduce the spread of the disease have the potential to exacerbate existing issues, including increasing food insecurity in households. Funding programmes were implemented to limit the impact of public-health measures on household and community food security. The overall effects of the actions are not yet understood. METHODS: This project used a qualitative approach to examine the determinants of food security and sovereignty and the impact of the COVID-19 pandemic policy responses on these determinants in Arviat and Iqaluit. Narrative analysis applied within a relational epistemology was used to describe the experiences of community members in Iqaluit and Arviat during the COVID-19 pandemic. RESULTS: Seven participants were interviewed in Iqaluit (n=3) and Arviat (n=4). Key themes included the importance of decolonisation for food sovereignty, the importance of food sharing to communities and the resilience of communities during COVID-19. Community members wished to see greater support and strengthening of the country (locally harvested) food economy to increase knowledge of food and harvesting skill, and for communities to find ways to reach residents who may fall through the cracks during times of need or crisis. CONCLUSIONS: This study is one of the first to document Nunavummiut experiences and perspectives of food security and sovereignty in Arviat and Iqaluit during the COVID-19 pandemic.

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.

Exploring ambivalence toward pregnancy among young Inuit women.

Ambivalence toward pregnancy is an important predictor of early pregnancy as documented in diverse Western societies. Inuit women from Nunavik, a northern region of Quebec, Canada, experience a high rate of early pregnancy, yet no study has explored their attitudes toward pregnancy. Grounded in a participatory approach, this study aimed to explore ambivalence toward pregnancy, among other pregnancy-related attitudes, and identify themes underlying ambivalence among young Inuit women from Nunavik. We conducted semi-structured interviews with 15 women aged 16 to 20 years, who became pregnant during the year preceding the interview. We used an inductive approach to analyse the data. Eleven participants were identified as ambivalent toward pregnancy while three were characterised as having a favourable attitude, and one as unfavourable. Four themes related to ambivalence were identified: the value of childbearing/motherhood; the use of contraceptives; the likelihood of becoming pregnant; and the ideal age to become pregnant. A better understanding of young women's attitudes toward pregnancy could contribute to the development of culturally relevant programmes to more effectively support adolescents, pregnant adolescents and young mothers, and to lead to better care.

Changes to acute-care hospitalizations among Indigenous children and youth: Results from the 2006 and 2011 Canadian Census Health and Environment Cohorts.

Background: This study described the differences in the hospitalization rates of First Nations children and youth living on and off reserve, Inuit children and youth living in Inuit Nunangat (excluding Nunavik), and Métis children and youth, relative to non-Indigenous children and youth and examined rate changes across 2006 and 2011. Data and methods: The 2006 and the 2011 Canadian Census Health and Environment Cohorts provided five years of hospital records that Statistics Canada linked to peoples' self-reported Indigenous identity as recorded on the census. Causes of hospitalizations were based on the most responsible diagnosis coded according to the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Canada, aggregated by chapter code. Age-standardized hospitalization rates (ASHRs) were calculated per 100,000 population. Rate ratios (RRs) were reported for each Indigenous group relative to non-Indigenous children and youth. Results: For the 2006 and the 2011 cohorts, ASHRs were generally higher among Indigenous children and youth than among non-Indigenous children and youth. For some health conditions, hospitalization patterns also varied across the two time periods within the given Indigenous groups. Among children, leading elevated RRs occurred for diseases of the respiratory system, the digestive system and injuries. Elevated mental health-related RRs were observed among all Indigenous groups for both cohort years of youth. Significant increases in mental health-related ASHRs were observed in 2011 compared with 2006 among all youth groups, except for Inuit youth living in Inuit Nunangat, possibly due in part to data limitations. Among Indigenous youth, elevated RRs were observed for pregnancy, childbirth and the puerperium, and for injuries. For all youth (except Inuit), childbirth-related ASHRs decreased in 2011 compared with 2006. Interpretation: Findings align with previously observed hospitalization disparities between Indigenous and non-Indigenous children and youth. These data enabled the tracking of changes over time to partly address national information gaps about population health outcomes for children and youth, namely hospitalization.

Inuit-defined determinants of food security in academic research focusing on Inuit Nunangat and Alaska: A scoping review protocol.

BACKGROUND: Academic research on food security in Inuit Nunangat and Alaska frequently adopts the Food and Agriculture Organization of the United Nations' working definition of food security and Western conceptualisations of what it means to be 'food secure'. However, in 2014, the Alaskan branch of the Inuit Circumpolar Council (ICC) stated that academic and intergovernmental definitions and understandings 'are important, but not what we are talking about when we say food security'. The organisation subsequently developed its own conceptualisation and definition: the Alaskan Inuit Food Security Conceptual Framework (AIFSCF), which in 2020 received informal assent by ICC-Canada. AIM: This protocol establishes a review strategy to examine how well academic research reflects Inuit conceptualisations and understandings of food security, as outlined in the AIFSCF. METHODS: Review structure and reporting will be completed according to adapted RepOrting standards for Systematic Evidence Syntheses (ROSES) guidelines. A comprehensive search strategy will be used to locate peer-reviewed research from Medline, Scopus, Web of Science and the Arctic and Antarctic Regions (EBSCO) databases. Dual reviewer screening will take place at the abstract, title, and full-text stages. Different study methodologies (qualitative, quantitative, and mixed methods) will be included for review, on the proviso that articles identify drivers of food security. An a priori coding framework will be applied by a single reviewer to extract data on publication characteristics, methods and article aims. Deductive thematic content analysis will then identify the frequency and precedence afforded within literature to the drivers and dimensions of food security identified by the AIFSCF.

Cancer disparities among non-Hispanic urban American Indian and Alaska Native populations in the United States, 1999-2017.

BACKGROUND: Disparities in cancer incidence have not been described for urban American Indian/Alaska Native (AI/AN) populations. The purpose of the present study was to examine incidence rates (2008-2017) and trends (1999-2017) for leading cancers in urban non-Hispanic AI/AN (NH AI/AN) compared to non-Hispanic White (NHW) populations living in the same urban areas. METHODS: Incident cases from population-based cancer registries were linked with the Indian Health Service patient registration database for improved racial classification of NH AI/AN populations. This study was limited to counties in Urban Indian Health Organization service areas. Analyses were conducted by geographic region. Age-adjusted rates (per 100,000) and trends (joinpoint regression) were calculated for leading cancers. RESULTS: Rates of colorectal, liver, and kidney cancers were higher overall for urban NH AI/AN compared to urban NHW populations. By region, rates of these cancers were 10% to nearly 4 times higher in NH AI/AN compared to NHW populations. Rates for breast, prostate, and lung cancer were lower in urban NH AI/AN compared to urban NHW populations. Incidence rates for kidney, liver, pancreatic, and breast cancers increased from 2% to nearly 7% annually between 1999 to 2017 in urban NH AI/AN populations. CONCLUSIONS: This study presents cancer incidence rates and trends for the leading cancers among urban NH AI/AN compared to urban NHW populations for the first time, by region, in the United States. Elevated risk of certain cancers among urban NH AI/AN populations and widening cancer disparities highlight important health inequities and missed opportunities for cancer prevention in this population.

Uncovering SARS-COV-2 vaccine uptake and COVID-19 impacts among First Nations, Inuit and Métis Peoples living in Toronto and London, Ontario.

BACKGROUND: First Nations, Inuit and Métis Peoples across geographies are at higher risk of SARS-CoV-2 infection and COVID-19 because of high rates of chronic disease, inadequate housing and barriers to accessing health services. Most Indigenous Peoples in Canada live in cities, where SARS-CoV-2 infection is concentrated. To address gaps in SARS-CoV-2 information for these urban populations, we partnered with Indigenous agencies and sought to generate rates of SARS-CoV-2 testing and vaccination, and incidence of infection for First Nations, Inuit and Métis living in 2 Ontario cities. METHODS: We drew on existing cohorts of First Nations, Inuit and Métis adults in Toronto (n = 723) and London (n = 364), Ontario, who were recruited using respondent-driven sampling. We linked to ICES SARS-CoV-2 databases and prospectively monitored rates of SARS-CoV-2 testing, diagnosis and vaccination for First Nations, Inuit and Métis, and comparator city and Ontario populations. RESULTS: We found that SARS-CoV-2 testing rates among First Nations, Inuit and Métis were higher in Toronto (54.7%, 95% confidence interval [CI] 48.1% to 61.3%) and similar in London (44.5%, 95% CI 36.0% to 53.1%) compared with local and provincial rates. We determined that cumulative incidence of SARS-CoV-2 infection was not significantly different among First Nations, Inuit and Métis in Toronto (7364/100 000, 95% CI 2882 to 11 847) or London (7707/100 000, 95% CI 2215 to 13 200) compared with city rates. We found that rates of vaccination among First Nations, Inuit and Métis in Toronto (58.2%, 95% CI 51.4% to 64.9%) and London (61.5%, 95% CI 52.9% to 70.0%) were lower than the rates for the 2 cities and Ontario. INTERPRETATION: Although Ontario government policies prioritized Indigenous populations for SARS-CoV-2 vaccination, vaccine uptake was lower than in the general population for First Nations, Inuit and Métis Peoples in Toronto and London. Ongoing access to culturally safe testing and vaccinations is urgently required to avoid disproportionate hospital admisson and mortality related to COVID-19 in these communities.

Kivalliq Inuit women travelling to Manitoba for birthing: findings from the Qanuinngitsiarutiksait study.

BACKGROUND: The Qanuinngitsiarutiksait study aimed to develop detailed profiles of Inuit health service utilization in Manitoba, by Inuit living in Manitoba (approximately 1,500) and by Inuit from the Kivalliq region of Nunavut who travel to Manitoba to access care not available in Nunavut (approximately 16,000 per year). METHODS: We used health administrative data routinely collected in Manitoba for all services provided and developed an algorithm to identify Inuit in the dataset. This paper focused on health services used by Inuit from the Kivalliq for prenatal care and birthing. RESULTS: Our study found that approximately 80 percent of births to women from the Kivalliq region occur in Manitoba, primarily in Winnipeg. When perinatal care and birthing are combined, they constitute one third of all consults happening by Kivalliq residents in Manitoba. For scale, hospitalizations for childbirths to Kivalliq women about to only 5 percent of all childbirth-related hospitalizations in Manitoba. CONCLUSIONS: The practice of evacuating women from the Kivalliq for perinatal care and birthing is rooted in colonialism, rationalized as ensuring that women whose pregnancy is at high risk have access to specialized care not available in Nunavut. While defendable, this practice is costly, and does not provide Inuit women a choice as to where to birth. Attempts at relocating birthing to the north have proven complex to operationalize. Given this, there is an urgent need to develop Inuit-centric and culturally appropriate perinatal and birthing care in Manitoba.

Genetic architecture and adaptations of Nunavik Inuit.

The Canadian Inuit have a distinct population background that may entail particular implications for the health of its individuals. However, the number of genetic studies examining this Inuit population is limited, and much remains to be discovered in regard to its genetic characteristics. In this study, we generated whole-exome sequences and genomewide genotypes for 170 Nunavik Inuit, a small and isolated founder population of Canadian Arctic indigenous people. Our study revealed the genetic background of Nunavik Inuit to be distinct from any known present-day population. The majority of Nunavik Inuit show little evidence of gene flow from European or present-day Native American peoples, and Inuit living around Hudson Bay are genetically distinct from those around Ungava Bay. We also inferred that Nunavik Inuit have a small effective population size of 3,000 and likely split from Greenlandic Inuit ∼10.5 kya. Nunavik Inuit went through a bottleneck at approximately the same time and might have admixed with a population related to the Paleo-Eskimos. Our study highlights population-specific genomic signatures in coding regions that show adaptations unique to Nunavik Inuit, particularly in pathways involving fatty acid metabolism and cellular adhesion (CPNE7, ICAM5, STAT2, and RAF1). Subsequent analyses in selection footprints and the risk of intracranial aneurysms (IAs) in Nunavik Inuit revealed an exonic variant under weak negative selection to be significantly associated with IA (rs77470587; P = 4.6 × 10-8).

Health-Related Behavioral Risk Factors and Obesity Among American Indians and Alaska Natives of the United States: Assessing Variations by Indian Health Service Region.

INTRODUCTION: Health-related behavioral risk factors and obesity are linked to high risk for multiple chronic diseases. We examined the prevalence of these risk factors among American Indians and Alaska Natives (AI/ANs) compared with that of non-Hispanic Whites and across Indian Health Service (IHS) regions. METHODS: We used 2017 Behavioral Risk Factor Surveillance System data from participants in 50 states and the District of Columbia to assess 4 behavioral risk factors (current cigarette smoking, heavy drinking, binge drinking, and physical inactivity) and obesity. We analyzed disparities in these risk factors between AI/AN and non-Hispanic White participants, nationwide and by IHS region, by conducting log-linear regression analyses while controlling for potential confounders. RESULTS: Nationwide, crude prevalence of current smoking, physical inactivity, and obesity were significantly higher among AI/AN than non-Hispanic White participants. After adjustment for sociodemographic characteristics, AI/AN participants were 11% more likely to report current smoking (P < .05) and 23% more likely to report obesity (P < .001) than non-Hispanic White participants. These patterns persisted in most IHS regions with some exceptions. In the Southwest region, AI/AN participants were 39% less likely to report current smoking than non-Hispanic White participants (P < .001). In the Pacific Coast region, compared with non-Hispanic White participants, AI/AN participants were 54% less likely to report heavy drinking (P < .01) but 34% more likely to report physical inactivity (P < .05). Across IHS regions, AI/AN participants residing in Alaska and the Northern Plains regions had the highest prevalence of current smoking and binge drinking, and those in the Southwest and Pacific Coast regions had the lowest prevalence of current smoking. AI/AN participants in the Southwest region had the lowest prevalence of physical inactivity, and those in the Southern Plains region had the highest prevalence of obesity. CONCLUSIONS: The findings of this study support the importance of public health efforts to address and improve behavioral risk factors related to chronic disease in AI/AN people, both nationwide and among IHS regions, through culturally appropriate interventions.

Cultural Safety as an Outcome of a Dynamic Relational Process: The Experience of Inuit in a Mainstream Residential Addiction Rehabilitation Centre in Southern Canada.

Few addiction treatment options are available in Arctic Canada, leading many Inuit to seek treatment programs in southern cities. We conducted a case study to understand what contributes to a culturally safe experience for Inuit in a mainstream addiction rehabilitation centre in Southern Canada. We carried out more than 700 hours of participant observation, in addition to semi-structured interviews and member-checking activities with 20 Inuit residents, 18 staff and four managers. Data were analysed using an inductive interpretative process. Throughout their journey in the program, Inuit navigated through contrasting situations and feelings that we grouped under six broad themes: having Inuit peers, having limitations imposed on one's ways of being and doing, facing ignorance and misperceptions, having conversations and dialogue, facing language barriers and being in a supportive and caring environment. This study highlights how cultural safety varies according to people, context and time, and relates to developing trustful relationships.

Physical activity attenuates postprandial hyperglycaemia in homozygous TBC1D4 loss-of-function mutation carriers.

AIMS/HYPOTHESIS: The common muscle-specific TBC1D4 p.Arg684Ter loss-of-function variant defines a subtype of non-autoimmune diabetes in Arctic populations. Homozygous carriers are characterised by elevated postprandial glucose and insulin levels. Because 3.8% of the Greenlandic population are homozygous carriers, it is important to explore possibilities for precision medicine. We aimed to investigate whether physical activity attenuates the effect of this variant on 2 h plasma glucose levels after an oral glucose load. METHODS: In a Greenlandic population cohort (n = 2655), 2 h plasma glucose levels were obtained after an OGTT, physical activity was estimated as physical activity energy expenditure and TBC1D4 genotype was determined. We performed TBC1D4-physical activity interaction analysis, applying a linear mixed model to correct for genetic admixture and relatedness. RESULTS: Physical activity was inversely associated with 2 h plasma glucose levels (ß[main effect of physical activity] -0.0033 [mmol/l] / [kJ kg-1 day-1], p = 6.5 × 10-5), and significantly more so among homozygous carriers of the TBC1D4 risk variant compared with heterozygous carriers and non-carriers (ß[interaction] -0.015 [mmol/l] / [kJ kg-1 day-1], p = 0.0085). The estimated effect size suggests that 1 h of vigorous physical activity per day (compared with resting) reduces 2 h plasma glucose levels by an additional ~0.7 mmol/l in homozygous carriers of the risk variant. CONCLUSIONS/INTERPRETATION: Physical activity improves glucose homeostasis particularly in homozygous TBC1D4 risk variant carriers via a skeletal muscle TBC1 domain family member 4-independent pathway. This provides a rationale to implement physical activity as lifestyle precision medicine in Arctic populations. DATA REPOSITORY: The Greenlandic Cardio-Metabochip data for the Inuit Health in Transition study has been deposited at the European Genome-phenome Archive ( https://www.ebi.ac.uk/ega/dacs/EGAC00001000736 ) under accession EGAD00010001428.

Molecular Epidemiology of Mycobacterium tuberculosis To Describe the Transmission Dynamics Among Inuit Residing in Iqaluit Nunavut Using Whole-Genome Sequencing.

BACKGROUND: In the last decade, tuberculosis (TB) incidence among Inuit in the Canadian Arctic has been rising. Our aim was to better understand the transmission dynamics of TB in this remote region of Canada using whole-genome sequencing. METHODS: Isolates from patients who had culture-positive pulmonary TB in Iqaluit, Nunavut, between 2009 and 2015 underwent whole-genome sequencing (WGS). The number of transmission events between cases within clusters was calculated using a threshold of a ≤3 single nucleotide polymorphism (SNP) difference between isolates and then combined with detailed epidemiological data using a reproducible novel algorithm. Social network analysis of epidemiological data was used to support the WGS data analysis. RESULTS: During the study period, 140 Mycobacterium tuberculosis isolates from 135 cases were sequenced. Four clusters were identified, all from Euro-American lineage. One cluster represented 62% of all cases that were sequenced over the entire study period. In this cluster, 2 large chains of transmission were associated with 3 superspreading events in a homeless shelter. One of the superspreading events was linked to a nonsanctioned gambling house that resulted in further transmission. Shelter to nonshelter transmission was also confirmed. An algorithm developed for the determination of transmission events demonstrated very good reproducibility (κ score .98, 95% confidence interval, .97-1.0). CONCLUSIONS: Our study suggests that socioeconomic factors, namely residing in a homeless shelter and spending time in a gambling house, combined with the superspreading event effect may have been significant factors explaining the rise in cases in this predominantly Inuit Arctic community.

Molecular Characterization and Antimicrobial Resistance in Neisseria gonorrhoeae, Nunavut Region of Inuit Nunangat, Canada, 2018-2019.

We assessed antimicrobial resistance (AMR) in Neisseria gonorrhoeae in Nunavut, Canada, using remnant gonorrhea nucleic acid amplification test-positive urine specimens. This study confirms the feasibility of conducting N. gonorrhoeae AMR surveillance and highlights the diversity of gonococcal sequence types and geographic variation of AMR patterns in the territory.

Active screening for tuberculosis in high-incidence Inuit communities in Canada: a cost-effectiveness analysis.

BACKGROUND: Active screening for tuberculosis (TB) involves systematic detection of previously undiagnosed TB disease or latent TB infection (LTBI). It may be an important step toward elimination of TB among Inuit in Canada. We aimed to evaluate the cost-effectiveness of community-wide active screening for TB infection and disease in 2 Inuit communities in Nunavik. METHODS: We incorporated screening data from the 2 communities into a decision analysis model. We predicted TB-related health outcomes over a 20-year time frame, beginning in 2019. We assessed the cost-effectiveness of active screening in the presence of varying outbreak frequency and intensity. We also considered scenarios involving variation in timing, impact and uptake of screening programs. RESULTS: Given a single large outbreak in 2019, we estimated that 1 round of active screening reduced TB disease by 13% (95% uncertainty range -3% to 27%) and was cost saving compared with no screening, over 20 years. In the presence of simulated large outbreaks every 3 years thereafter, a single round of active screening was cost saving, as was biennial active screening. Compared with a single round, we also determined that biennial active screening reduced TB disease by 59% (95% uncertainty range 52% to 63%) and was estimated to cost Can$6430 (95% uncertainty range -$29 131 to $13 658 in 2019 Can$) per additional active TB case prevented. With smaller outbreaks or improved rates of treatment initiation and completion for people with LTBI, we determined that biennial active screening remained reasonably cost-effective compared with no active screening. INTERPRETATION: Active screening is a potentially cost-saving approach to reducing disease burden in Inuit communities that have frequent TB outbreaks.