Population In Northern Sweden Research Articles

Hearing impairment and vestibular function in patients with a pathogenic splice variant in the LHX3 gene

BackgroundLHX3 is a gene encoding a LIM-homeodomain transcription factor important for the fetal development of several organs, such as the pituitary gland, spinal motor neurons and the inner ear. Pathogenic and likely pathogenic variants in the LHX3 gene are infrequent and result in a rare syndrome known as combined pituitary hormone deficiency-3, CPHD3.MethodsWe have studied hearing and vestibular functions in a group of eight individuals, aged 8–36 years, all of whom were homozygous for a specific variant in the LHX3 gene at chromosome 9q34. We reexamined the results of consecutive hearing tests from newborn until April 2024. ResultsOur data showed that all the tested patients had progressive sensorineural hearing deficiency ranging from moderately severe to complete loss. We have performed vestibular testing in six patients and, for the first time, demonstrated that a mutation in the LHX3 gene not only affects hearing, but is also associated with vestibular impairment.ConclusionThe human pathogenic variant c.455-2A > G in the LHX3 gene on chromosome 9q34, which present as a founder mutation in the population in northern Sweden, is responsible for phenotypes associated with progressive hearing loss and balance impairment. These findings prove that the LHX3 gene is crucial for the function of both the cochlear and vestibular organs.

Mendelian randomization supports causal effects of inflammatory biomarkers on myopic refractive errors.

To determine whether inflammatory biomarkers are causal risk factors for more myopic refractive errors. Northern Sweden Population Health Study (NSPHS), providing inflammatory biomarkers data; UK Biobank, providing refractive errors data. 95,619 European men and women aged 40 to 69 years with available information of refractive errors and inflammatory biomakers. Inflammatory biomarkers including ADA, CCL23, CCL25, CD6, CD40, CDCP-1, CST5, CXCL-5, CXCL-6, CXCL-10, IL-10RB, IL-12B, IL-15RA, IL-18R1, MCP-2, MMP-1, TGF-β1, TNF-β, TWEAK and VEGF-A were exposures, and spherical equivalent (SE) using the formula SE = sphere + (cylinder/2) was outcome. Mendelian randomization analyses showed that each unit increase in VEGF-A, CD6, MCP-2 were causally related to a more myopic refractive errors of 0.040 D/pg.mL-1 (95% confidence interval 0.019 to 0.062; P = 2.031 × 10-4), 0.042 D/pg.mL-1 (0.027 to 0.057; P = 7.361 × 10-8) and 0.016 D/pg.mL-1 (0.004 to 0.028; P = 0.009), and each unit increase in TWEAK was causally related to a less myopic refractive errors of 0.104 D/pg.mL-1 (-0.152 to -0.055; P = 2.878 × 10-5). Tested by the MR-Egger, weighted median, MR-PRESSO, Leave-one-out methods, our results were robust to horizontal pleiotropy and heterogeneity in VEGF-A, MCP-2, CD6, but not in TWEAK. Our Mendelian Randomization analysis supported the causal effects of VEGF-A, MCP-2, CD6 and TWEAK on myopic refractive errors. These findings are important for providing new indicators for early intervention of myopia to make myopic eyesight threatening consequences less inevitable.

Food protein-induced enterocolitis syndrome among children in northern Sweden-A retrospective review from 2004-2018.

To describe clinical presentation and development of tolerance among children with Food protein-induced enterocolitis syndrome (FPIES) in a population in northern Sweden. A retrospective review of medical records of children presenting with FPIES symptoms from 1 January 2004, to 31 May 2018. Sixty children (65% boys) with FPIES were included. The estimated incidence gradually increased to 0.45% in 2016-2017. The most common food triggers were cow's milk (40%), fish (37%) and oat (23%). Symptoms presented in 31 (60%) children before 6 months and in 57 (95%) before 1 year of age. The median age for FPIES diagnosis was 7 (range 3-134) months and for fish FPIES 13 (range 7-134) months. By 3 years of age, 67% of children with FPIES to milk and oat but none of the children with fish FPIES had developed tolerance. Allergic conditions like eczema and asthma were reported in 52% of the children. The cumulative FPIES incidence was 0.45% in 2016-2017. Most children presented with symptoms before 1 year of age, but the diagnosis was often delayed, especially for FPIES to fish. Tolerance development occurred at an earlier age when FPIES was triggered by milk and oat compared to fish.

Kidney function in patients with bipolar disorder with and without lithium treatment compared with the general population in northern Sweden: results from the LiSIE and MONICA cohorts

The clinical relevance of lithium nephropathy is subject to debate. Kidney function decreases with age and comorbidities, and this decline might lead to attribution bias when erroneously ascribed to lithium. We aimed to investigate whether patients with bipolar or schizoaffective disorder had faster decline in estimated glomerular filtration rate (eGFR) compared with the general population, whether observed differences in the steepness of the decline were attributable to lithium, and whether such changes depended on the length of lithium exposure. In this cross-sectional cohort study, we used clinical data from the Lithium-Study into Effects and Side-effects (LiSIE) retrospective cohort study, which included patients with bipolar disorder or schizoaffective disorder whose medical records were reviewed up to Dec 31, 2017, and the WHO Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) study, covering a representative sample of the general population in northern Sweden aged 25-74 years. The primary outcome was the age-associated decline of creatinine-based eGFR, assessed using linear regression. We adjusted for sex and grouped for different lengths of lithium exposure (never or <1 year, 1-5 years, >5-10 years, and >10 years). For patients with moderate-to-severe kidney disease we identified the underlying nephropathy in the case records. From LiSIE, we included 785 patients (498 [63%] female and 287 [37%] male), with a mean age of 49·8 years (SD 13·2; range 25-74). From MONICA, we included 1549 individuals (800 [52%] female and 749 [48%] male), with a mean age of 51·9 years (13·8; 25-74). No ethnicity data were collected. Adjusted for duration of lithium exposure, eGFR declined by 0·57 mL/min/1·73 m2/year (95% CI 0·50-0·63) in patients with bipolar disorder or schizoaffective disorder and by 0·57 mL/min/1·73 m2/year (0·53-0·61) in the reference population. Lithium added 0·54 mL/min/1·73 m2 (0·43-0·64) per year of treatment (p<0·0001). After more than 10 years on lithium, decline was significantly steeper than in all other groups including the reference population (p<0·0001). Lithium nephropathy was judged to be the commonest cause of moderate-to-severe chronic kidney disease, but comorbidities played a role. The effect of lithium on eGFR showed a high degree of inter-individual variation. Steeper eGFR decline in patients with bipolar disorder or schizoaffective disorder can be attributed to lithium, but the trajectory of kidney function decline varies widely. Comorbidities affecting kidneys should be treated assertively as one possible means to affect the trajectory. In patients with a fast trajectory, a trade-off is required between continuing lithium to treat mental health problems and discontinuing lithium for the sake of renal health. Norrbotten County Research and Learning Fund Sweden, Visare Norr (Northern County Councils Regional Federation Fund), Swedish Kidney Foundation (Njurfonden), Swedish Kidney Association (Njurförbundet), Norrbotten section. For the Swedish translation of the Summary see Supplementary Materials section.

Incidence, remission, and persistence of Raynaud’s phenomenon in the general population of northern Sweden: a prospective study

BackgroundRaynaud’s phenomenon is common condition, but little is known about the natural course. The primary aim of this study was to determine the incidence, remission, and persistence proportions of Raynaud’s phenomenon in the general population of northern Sweden. Secondary aims were to determine how individual and exposure factors affect the course of Raynaud’s phenomenon, and to assess gender differences.MethodsA prospective, survey-based, closed-cohort study was conducted on a sample of men and women between 18–70 years of age, living in northern Sweden. Data on Raynaud’s phenomenon characteristics and general health status were collected during the winters of 2015 (baseline) and 2021 (follow-up). Rates of incidence, remission, and persistence were calculated. Binary logistic regression was used to determine the association between baseline variables and the course of Raynaud’s phenomenon. Results: The study population consisted of 2703 women (53.9%) and 2314 men. There were 390 women (14.5%) and 290 men (12.7%) reporting Raynaud’s phenomenon in the follow-up survey. The annual incidence proportion was 0.7% among women and 0.9% among men (gender difference p = 0.04). The annual remission proportion was 4.4% and 5.5%, respectively (p = 0.05). Having sustained a cold injury affecting the hands since baseline was significantly associated with incident Raynaud’s phenomenon (OR 3.92; 95% CI 2.60–5.90), after adjusting for age and gender.ConclusionsIn the general population of northern Sweden, Raynaud’s phenomenon is a common but variable condition, where symptoms may remit over time. Men had a higher incidence proportion than women. The results support a possible causal pathway where cold injury can precede the onset of Raynaud’s phenomenon.

The impact of Raynaud's phenomenon on work ability - a longitudinal study.

ObjectiveTo determine if having Raynaud’s phenomenon (RP) affects the work ability, job retainment, or occurrence of sick leave.MethodsSurveys on the working-age general population of northern Sweden were conducted in 2015 and 2021, gathering data on RP, occupation and sick leave. Work ability was assessed using the Work Ability Score.ResultsThe study population consisted of 2,703 women and 2,314 men, among which 390 women and 290 men reported RP at follow-up. For women, the mean [standard deviation (SD)] Work Ability Score was 8.02 (2.24) for subjects reporting RP and 7.68 (2.46) for those without RP. For men, the corresponding numbers were 7.37 (2.03) and 7.61 (2.14), respectively. Multiple linear regression did not show an association between RP status and work ability (p = 0.459 for women and p = 0.254 for men), after adjusting for age, body mass index, physical workload, cardiovascular disease, and perceived stress. Having retained the same main livelihood since baseline was reported by 227 (58.5%) women with RP, 1,163 (51.2%) women without RP, 152 (52.6%) men with RP, and 1,075 (54.1%) men without RP (p = 0.002 for women and p = 0.127 for men). At follow-up, any occurrence of sick leave during the last year was reported by 80 (21.4%) women with RP, 410 (18.6%) women without RP, 48 (17.1%) men with RP, and 268 (13.7%) men without RP (p = 0.208 for women and p = 0.133 for men). Among those reporting sick leave, the mean (SD) duration in months was 2.93 (3.76) for women with RP, 3.00 (4.64) for women without RP, 2.77 (3.79) for men with RP, and 2.91 (12.45) for men without RP (p = 0.849 for women and p = 0.367 for men).ConclusionFor neither women nor men was there a significant effect of having RP on work ability. Women with RP reported a slightly higher job retainment compared to those without the condition, while there was no difference in job retainment among men. For neither gender did the presence of RP influence the occurrence of recent sick leave, nor did it affect the length of time away from work.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12995-022-00354-2.

Ambient temperature and stillbirth risks in northern Sweden, 1880-1950.

Climate vulnerability of the unborn can contribute to adverse birth outcomes, in particular, but it is still not well understood. We investigated the association between ambient temperature and stillbirth risk among a historical population in northern Sweden (1880-1950). We used digitized parish records and daily temperature data from the study region covering coastal and inland communities some 600 km north of Stockholm, Sweden. The data included 141,880 births, and 3,217 stillbirths, corresponding to a stillbirth rate of 22.7 (1880-1950). The association between lagged temperature (0-7 days before birth) and stillbirths was estimated using a time-stratified case-crossover design. Incidence risk ratios (IRR) with 95% confidence intervals were computed, and stratified by season and sex. We observed that the stillbirth risk increased both at low and high temperatures during the extended summer season (April to September), at -10°C, and the IRR was 2.3 (CI 1.28, 4.00) compared to the minimum mortality temperature of +15°C. No clear effect of temperature during the extended winter season (October to March) was found. Climate vulnerability was greater among the male fetus compared to the female counterparts. In this subarctic setting before and during industrialization, both heat and cold during the warmer season increased the stillbirth risk. Urbanization and socio-economic development might have contributed to an uneven decline in climate vulnerability of the unborn.

Daily moderate-intensity physical activities and optimism promote healthy ageing in rural northern Sweden: a cross-sectional study.

ABSTRACT The aim of our study was to explore the association between self-reported health factors and self-rated health (SRH) among an older rural population in northern Sweden and whether confounders optimistic outlook or daily moderate-intensity physical activity could moderate the association between self-reported health factors and SRH, controlling for age. The study is based on a sample (N = 1946) from the “Health on Equal Terms” Västernorrland survey 2018 aged 65–84. Prevalence and multivariate logistic regression analyses were performed. The results indicated most rural older people perceived very good or good SRH, though physical and mental health issues and impaired mobility increased with advanced age. Mental well-being exhibited a stronger association with poor SRH than physical health or impaired mobility. In addition, confounders optimistic outlook and daily moderate-intensity physical activity, separately and together could moderate the association between health factors and poor SRH. In conclusion, older people in a rural setting perceived good health, despite common physical and mental health issues. Promoting daily moderate-intensity physical activity and activities contributing to an optimistic outlook can protect against poor SRH in old age.

LQTS founder population in Northern Sweden – the natural history of a potentially fatal inherited cardiac disorder

ABSTRACT Long QT Syndrome (LQTS) is an autosomal dominant inherited cardiac disorder associated with life-threatening arrhythmias. In northern Sweden, a LQTS founder mutation (p.Y111C, KCNQ1 gene) was verified by genetic haplotype analysis and genealogical studies, and a common ancestor couple was identified. Clinical studies of this population revealed an apparent mild phenotype. However, due to early commencement of prophylactic treatment, the natural history of this disorder cannot be properly assessed based only on clinical data. By using the family tree mortality ratio method (FTMR), we assessed the natural history of the untreated LQTS founder population. The principle of FTMR is to compare the age-specific mortality rates in a historic population harboring an inherited disorder with the corresponding mortality rates in an unaffected control population. Initially, we used the general Swedish population during the same period for comparison and observed an apparent increased longevity in the p.Y111C study population. However, when using a control population born in the same area, we observed no differences regarding overall mortality. Moreover, patterns suggesting age- and sex-stratified excess mortality, in accordance with previous LQTS studies, were evident. This study shows the importance of being aware of historical demographic patterns to avoid misinterpreting when comparing historical data.

Remission of adult-onset asthma is rare: a 15-year follow-up study.

BackgroundThere are few long-term clinical follow-up studies of adult-onset asthma. The aim of this article was to study clinical characteristics of adult-onset asthma in relation to remission and persistence of the disease in a 15-year follow-up.MethodsA cohort of 309 adults aged 20–60 years with asthma onset during the last 12 months verified by bronchial variability, was recruited between 1995 and 1999 from the general population in northern Sweden. The cohort was followed-up in 2003 (n=250) and between 2012 and 2014 (n=205). Structured interviews and spirometry were performed at recruitment and the follow-ups. Bronchial hyperreactivity (BHR) and skin-prick tests were performed at recruitment and blood samples were collected at the last follow-up. Remission of asthma was defined as no asthma symptoms and no use of asthma medication during the last 12 months.ResultsOf eight individuals in remission in 2003, five had relapsed between 2012 and 2014 and in total, 23 (11%) were in remission, while 182 had persistent asthma. Those in remission had higher mean forced expiratory volume in 1 s % predicted at recruitment than those with persistent asthma (94.6 versus 88.3, p=0.034), fewer had severe BHR (27.3% versus 50.9%, p=0.037) and they had less body mass index increase (+1.6 versus +3.0, p=0.054). Of those with persistent asthma, 13% had uncontrolled asthma and they had higher levels of blood neutrophils than those with partly controlled or controlled asthma.ConclusionHigher forced expiratory volume in 1 s % predicted and less-severe BHR was associated with remission of adult-onset asthma, but still, the proportion in remission in this 15-year follow-up was low.

A whole-genome sequenced control population in northern Sweden reveals subregional genetic differences

The number of national reference populations that are whole-genome sequenced are rapidly increasing. Partly driving this development is the fact that genetic disease studies benefit from knowing the genetic variation typical for the geographical area of interest. A whole-genome sequenced Swedish national reference population (n = 1000) has been recently published but with few samples from northern Sweden. In the present study we have whole-genome sequenced a control population (n = 300) (ACpop) from Västerbotten County, a sparsely populated region in northern Sweden previously shown to be genetically different from southern Sweden. The aggregated variant frequencies within ACpop are publicly available (DOI 10.17044/NBIS/G000005) to function as a basic resource in clinical genetics and for genetic studies. Our analysis of ACpop, representing approximately 0.11% of the population in Västerbotten, indicates the presence of a genetic substructure within the county. Furthermore, a demographic analysis showed that the population from which samples were drawn was to a large extent geographically stationary, a finding that was corroborated in the genetic analysis down to the level of municipalities. Including ACpop in the reference population when imputing unknown variants in a Västerbotten cohort resulted in a strong increase in the number of high-confidence imputed variants (up to 81% for variants with minor allele frequency < 5%). ACpop was initially designed for cancer disease studies, but the genetic structure within the cohort will be of general interest for all genetic disease studies in northern Sweden.

Increased cancer risk in male hunters compared to the general male population in Northern Sweden after the Chernobyl Nuclear Power Plant accident?

Background:Male hunters in Swedish counties with high fallout of 137Cs after the Chernobyl Nuclear Power Plant (NPP) accident have higher radiation exposure due to higher consumption of game compared with the general population.Methods:Cancer incidence in Sweden was studied in 9 counties with different 137Cs fallout after the Chernobyl NPP accident in 1986. In total, 9,267 cancer cases occurred in hunters and 138,909 cancer cases in non-hunters to 31 December 2015. Incidence rate ratios (IRR) with 95% confidence intervals (CI) were calculated using unexposed hunters, or non-hunters, as reference to study internal radiation exposure or hunter life style, respectively.Results:Directly age standardized total cancer incidence showed an increasing trend in non-hunters. For hunters, the total cancer incidence was significantly lower up to 2001 when the total cancer incidence crossed over the weaker non-hunter trend and remained higher for the following 15 years. IRRs for total cancer in hunters versus non-hunters for each county did not show any clear exposure response pattern. IRRs for hunters versus non-hunters were higher regardless of rural/non-rural status with slightly higher risk estimates for the rural settings. The IRR for hunters was 1.06 (95% CI 1.04–1.08) 1986–2015, representing an excess of 531 cancer cases in hunters.Conclusion:An increased total incidence of cancer was identified for male hunters compared with male non-hunters. No obvious association between cancer and 137Cs from the Chernobyl NPP accident could be identified, although the exposure classification was too crude to exclude such an association.

Transcriptome analysis of fibroblasts from schizophrenia patients reveals differential expression of schizophrenia-related genes

Schizophrenia is a complex neurodevelopmental disorder with high rate of morbidity and mortality. While the heritability rate is high, the precise etiology is still unknown. Although schizophrenia is a central nervous system disorder, studies using peripheral tissues have also been established to search for patient specific biomarkers and to increase understanding of schizophrenia etiology. Among all peripheral tissues, fibroblasts stand out as they are easy to obtain and culture. Furthermore, they keep genetic stability for long period and exhibit molecular similarities to cells from nervous system. Using a unique set of fibroblast samples from a genetically isolated population in northern Sweden, we performed whole transcriptome sequencing to compare differentially expressed genes in seven controls and nine patients. We found differential fibroblast expression between cases and controls for 48 genes, including eight genes previously implicated in schizophrenia or schizophrenia related pathways; HGF, PRRT2, EGR1, EGR3, C11orf87, TLR3, PLEKHH2 and PIK3CD. Weighted gene correlation network analysis identified three differentially co-expressed networks of genes significantly-associated with schizophrenia. All three modules were significantly suppressed in patients compared to control, with one module highly enriched in genes involved in synaptic plasticity, behavior and synaptic transmission. In conclusion, our results support the use of fibroblasts for identification of differentially expressed genes in schizophrenia and highlight dysregulation of synaptic networks as an important mechanism in schizophrenia.

Dairy Products and Cancer Risk in a Northern Sweden Population

The role of dairy products in cancer is unclear. We assessed consumption of fermented milk, non-fermented milk, cheese, and butter, estimated from semi-quantitative food frequency questionnaires, in relation to prospective risk of breast, prostate, colorectal, smoking-, and obesity-related cancers in 101,235 subjects, including 12,552 cancer cases, in the population-based Northern Sweden Health and Disease Study. Most analyses (n = 20) rendered null results. In men, we observed an increased prostate cancer risk among high-consumers of cheese (hazard ratio (HR) for highest vs. lowest quintile (Q5–Q1), 1.11; 95% CI, 0.97–1.27; Ptrend = 0.013). In women, high-consumers of cheese had a decreased risk of overall cancer (HR Q5–Q1, 0.95; 95% CI, 0.88–1.04; Ptrend = 0.039), smoking-related (HR Q5–Q1, 0.84; 95% CI, 0.72–0.97; Ptrend ≤ 0.001), and colorectal cancers (HR Q5–Q1, 0.82; 95% CI, 0.63–1.07; Ptrend = 0.048). Butter yielded a weak decreased obesity-related cancer risk in women (HR Q5–Q1, 0.91; 95% CI, 0.81–1.02; Ptrend = 0.049). Fermented milk yielded HRs below zero in women, but with no clear linear associations. In conclusion, this study does not support any major adverse or beneficial effects of fermented milk, non-fermented milk, cheese, and butter in the diet from a cancer risk perspective.

Tuberculosis in the Circumpolar Region, 2006–2012

The northern circumpolar jurisdictions Canada (Northwest Territories, Nunavik, Nunavut, Yukon), Finland, Greenland, Norway, Russian Federation (Arkhangelsk), Sweden and the United States (Alaska). To describe and compare demographic, clinical and laboratory characteristics, including drug resistance and treatment completion, of tuberculosis (TB) cases in the northern circumpolar populations. 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. 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. 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.

Time trends and exposure determinants of lead and cadmium in the adult population of northern Sweden 1990–2014

IntroductionThis study follows cadmium and lead concentrations in blood in the adult population in northern Sweden over 24 years. Material and methodsConcentrations of lead and cadmium were measured in single whole blood samples (B-Pb and B-Cd) from 619 men and 926 women participating in the Northern Sweden WHO MONICA Study on one occasion 1990–2014. Associations with smoking and dietary factors were investigated. Consumption of moose meat was asked for in 2014. ResultsIn the adult population in northern Sweden, the median B-Pb in 2014 was 11.0µg/L in young (25–35 years) men and 9.69µg/L in young women. In an older age-group (50–60 years), the median B-Pb was 15.1µg/L in men and 13.1µg/L in women. B-Pb decreased from 1990 to 2009, after which time no further decrease was observed. B-Pb was higher in smokers than in non-smokers. In never-smokers, positive associations were found between B-Pb and consumption of wine and brewed coffee (women only) in 2004–2014. Higher B-Pb with consumption of moose meat was demonstrated in men, but not in women. B-Cd was essentially stable over the whole period, but an increase in B-Cd, of 3% per year, was detected in never-smoking women between 2009 and 2014. In 2014, median B-Cd in never-smokers in the four groups was; 0.11µg/L in younger men, 0.15µg/L in younger women, 0.14µg/L in older men, and 0.21µg/L in older women. B-Cd was higher in smokers than in non-smokers. The only positive association between B-Cd and food items in 2004–2014 was with consumption of brewed coffee (men only). ConclusionsThe lack of a decrease in B-Cd from 1990 to 2014 and the absence of a further decrease in B-Pb after 2009 are unsatisfactory considering the health risks these metals pose in the general population at current concentrations.

Association of CD247 (CD3ζ) gene polymorphisms with T1D and AITD in the population of northern Sweden.

BackgroundT1D and AITD are autoimmune disorders commonly occurring in the same family and even in the same individual. The genetic contribution to these disorders is complex making uncovering of susceptibility genes very challenging. The general aim of this study was to identify loci and genes contributing to T1D/AITD susceptibility. Our strategy was to perform linkage and association studies in the relatively genetically homogenous population of northern Sweden. We performed a GWLS to find genomic regions linked to T1D/AITD in families from northern Sweden and we performed an association study in the families to test for association between T1D/AITD and variants in previously published candidate genes as well as a novel candidate gene, CD247.MethodsDNA prepared from 459 individuals was used to perform a linkage and an association study. The ABI PRISM Linkage Mapping Set v2.5MD10 was employed for an initial 10-cM GWLS, and additional markers were added for fine mapping. Merlin was used for linkage calculations. For the association analysis, a GoldenGate Custom Panel from Illumina containing 79 SNPs of interest was used and FBAT was used for association calculations.ResultsOur study revealed linkage to two previously identified chromosomal regions, 4q25 and 6p22, as well as to a novel chromosomal region, 1q23. The association study replicated association to PTPN22, HLA-DRB1, INS, IFIH1, CTLA4 and C12orf30. Evidence in favor of association was also found for SNPs in the novel susceptibility gene CD247.ConclusionsSeveral risk loci for T1D/AITD identified in published association studies were replicated in a family material, of modest size, from northern Sweden. This provides evidence that these loci confer disease susceptibility in this population and emphasizes that small to intermediate sized family studies in this population can be used in a cost-effective manner for the search of genes involved in complex diseases. The linkage study revealed a chromosomal region in which a novel T1D/AITD susceptibility gene, CD247, is located. The association study showed association between T1D/AITD and several variants in this gene. These results suggests that common susceptibility genes act in concert with variants of CD247 to generate genetic risk for T1D/AITD in this population.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-016-0333-z) contains supplementary material, which is available to authorized users.

Epigenome-wide association study reveals differential DNA methylation in individuals with a history of myocardial infarction.

Cardiovascular diseases (CVDs) are the leading causes of death worldwide and represent a substantial economic burden on public health care systems. Epigenetic markers have potential as diagnostic markers before clinical symptoms have emerged, and as prognostic markers to inform the choice of clinical intervention. In this study, we performed an epigenome-wide association study (EWAS) for CVDs, to identify disease-specific alterations in DNA methylation. CpG methylation in blood samples from the northern Sweden population health study (NSPHS) (n = 729) was assayed on the Illumina Infinium HumanMethylation450 BeadChip. Individuals with a history of a CVD were identified in the cohort. It included individuals with hypertension (N = 147), myocardial infarction (MI) (N = 48), stroke (N = 27), thrombosis (N = 22) and cardiac arrhythmia (N = 5). Differential DNA methylation was observed at 211 CpG-sites in individuals with a history of MI (q <0.05). These sites represent 196 genes, of which 42 have been described in the scientific literature to be related to cardiac function, cardiovascular disease, cardiogenesis and recovery after ischemic injury. We have shown that individuals with a history of MI have a deviating pattern of DNA methylation at many genomic loci of which a large fraction has previously been linked to CVD. Our results highlight genes that might be important in the pathogenesis of MI or in recovery. In addition, the sites pointed out in this study can serve as candidates for further evaluation as potential biomarkers for MI.

Spatial and temporal variation in the distribution and abundance of red foxes in the tundra and taiga of northern Sweden

Variation in the distribution and abundance of animals in space and time are key concepts of population ecology. We studied these variations in a population of red foxes (Vulpes vulpes) in the tundra and taiga of northern Sweden. We analysed 12 years (1974–1985) of snow tracking data from a large area of 65,375 km2. Specifically, we evaluated to what extent the distribution of red foxes was explained by the presence of prey and how this interacted with snow depth and altitude. We also tested for temporal linear trends in the distribution and abundance of red foxes during the study period. The distribution of red foxes was explained by the presence of rodents, hares, tetraonid species, and ungulates (i.e. carcasses). Snow depth had a negative effect on the impact of small prey on the distribution of the red foxes, whereas it had a positive effect on the impact of ungulates. The influence of hares increased with altitude. Neither distribution nor abundance of red foxes showed a positive or negative linear trend, suggesting a stable population in northern Sweden during our study. This study showed that the distribution of red foxes was not only influenced by the presence of their main prey (rodents), but also by interactions between alternative prey, altitude, and snow depth. This study also emphasizes the importance of ungulate carcasses for red foxes and for wildlife management.

A network of synaptic genes associated with schizophrenia and bipolar disorder

Identification of novel candidate genes for schizophrenia (SZ) and bipolar disorder (BP), two psychiatric disorders with large epidemiological impacts, is a key research area in neurosciences and psychiatric genetics. Previous evidence from genome-wide studies suggests an important role for genes involved in synaptic plasticity in the risk for SZ and BP. We used a convergent genomics approach, combining different lines of biological evidence, to identify genes involved in the cAMP/PKA/CREB functional pathway that could be novel candidates for BP and SZ: CREB1, CREM, GRIN2C, NPY2R, NF1, PPP3CB and PRKAR1A. These 7 genes were analyzed in a HapMap based association study comprising 48 common SNPs in 486 SZ, 351 BP patients and 514 control individuals recruited from an isolated population in Northern Sweden. Genetic analysis showed significant allelic associations of SNPs in PRKAR1A with SZ and of PPP3CB and PRKAR1A with BP. Our results highlight the feasibility and the importance of convergent genomic data analysis for the identification of candidate genes and our data provide support for the role of common inherited variants in synaptic genes and their involvement in the etiology of BP and SZ.