The social patterning of health, smoking and drinking in Estonia, Latvia, Lithuania and Finland in 1994-2004

The Baltic countries share public health problems typical of most Eastern European transition economies: morbidity and mortality from non-communicable diseases is higher than in Western European countries. This situation has many similarities compared to a neighbouring country, Finland during the late 1960s. There are reasons to expect that health disadvantage may be increasing among the less advantaged population groups in the Baltic countries. The evidence on social differences in health in the Baltic countries is, however, scattered to studies using different methodologies making comparisons difficult. This study aims to bridge the evidence gap by providing comparable standardized cross-sectional and time trend analyses to the social patterning of variation in health and two key health behaviours i.e. smoking and drinking in Estonia, Latvia, Lithuania and Finland in 1994-2004 representing Eastern European transition countries and a stable Western European country. The data consisted of similar cross-sectional postal surveys conducted in 1994, 1996, 1998, 2000, 2002 and 2004 on adult populations (aged 20 64 years) in Estonia (n=9049), Latvia (n=7685), Lithuania (n=11634) and Finland (n=18821) in connection with the Finbalt Health Monitor project. The main statistical method was logistic regression analysis. Perceived health was found to be worse among both men and women in the Baltic countries than in Finland. Poor health was associated with older age and lower education in all countries studied. Urbanization and marital status were not consistently related to health. The existing educational inequalities in health remained generally stable over time from 1994 to 2004. In the Baltic countries, however, improvement in perceived health was mainly found among the better educated men and women. Daily smoking was associated with young age, lower education and psychological distress in all countries. Among women smoking was also associated with urbanisation in all countries except Estonia. Among Lithuanian women, the educational gradient in smoking was weakest, and the overall prevalence of smoking increased over time. Drinking was generally associated with young age among men and women, and with education among women. Better educated women were more often frequent drinkers and less educated binge drinkers. The exception was that in Latvian men and women both frequent drinking and binge drinking were associated with low education. In conclusion, the Baltic countries are likely to resemble Western European countries rather than other transition societies. While health inequalities did not markedly change, substantial inequalities do remain, and there were indications of favourable developments mainly among the better educated. Pressures towards increasing health inequalities may therefore be visible in the future, which would be in accordance with the results on smoking and drinking in this study.

Meta-analysis of genome-wide association for migraine in six population-based European cohorts

Migraine is a common neurological disorder with a genetically complex background. This paper describes a meta-analysis of genome-wide association (GWA) studies on migraine, performed by the Dutch-Icelandic migraine genetics (DICE) consortium, which brings together six population-based European migraine cohorts with a total sample size of 10,980 individuals (2446 cases and 8534 controls). A total of 32 SNPs showed marginal evidence for association at a P-value<10(-5). The best result was obtained for SNP rs9908234, which had a P-value of 8.00 x 10(-8). This top SNP is located in the nerve growth factor receptor (NGFR) gene. However, this SNP did not replicate in three cohorts from the Netherlands and Australia. Of the other 31 SNPs, 18 SNPs were tested in two replication cohorts, but none replicated. In addition, we explored previously identified candidate genes in the meta-analysis data set. This revealed a modest gene-based significant association between migraine and the metadherin (MTDH) gene, previously identified in the first clinic-based GWA study (GWAS) for migraine (Bonferroni-corrected gene-based P-value=0.026). This finding is consistent with the involvement of the glutamate pathway in migraine. Additional research is necessary to further confirm the involvement of glutamate.

Molecular Genetics of Schizophrenia and Related Intermediate Phenotypes in a Founder Population

Schizophrenia, affecting about 1% of population worldwide, is a severe mental disorder characterized by positive and negative symptoms, such as psychosis and anhedonia, as well as cognitive deficits. At present, schizophrenia is considered a complex disorder of neurodevelopmental origin with both genetic and environmental factors contributing to its onset. Although a number of candidate genes for schizophrenia have been highlighted, only very few schizophrenia patients are likely to share identical genetic liability. This study is based on the nation-wide schizophrenia family sample of the National Institute for Health and Welfare, and represents one of the largest and most well-characterized familial series in the world. In the first part of this study, we investigated the roles of the DTNBP1, NRG1, and AKT1 genes in the background of schizophrenia in Finland. Although these genes are associated with schizophrenia liability in several populations, any significant association with clinical diagnostic information of schizophrenia remained absent in our sample of 441 schizophrenia families. In the second part of this study, we first replicated schizophrenia linkage on the long arm of chromosome 7 in 352 schizophrenia families. In the following association analysis, we utilized additional clinical disorder features and intermediate phenotypes – endophenotypes - in addition to diagnostic information from altogether 290 neuropsychologically assessed schizophrenia families. An intragenic short tandem repeat allele of the regional RELN gene, supposed to play a role in the background of several neurodevelopmental disorders, showed significant association with poorer cognitive functioning and more severe schizophrenia symptoms. Additionally, this risk allele was significantly more prevalent among the individuals affected with schizophrenia spectrum disorders. We have previously identified linkage of schizophrenia and its cognitive endophenotypes on the long arms of chromosomes 2, 4, and 5. In the last part of this study, we selected altogether 104 functionally relevant candidate genes from the linked regions. We detected several promising associations, of which especially interesting are the ERBB4 gene, showing association with the severity of schizophrenia symptoms and impairments in traits related to verbal abilities, and the GRIA1 gene, showing association with the severity of schizophrenia symptoms. Our results extend the previous evidence that the genetic risk for schizophrenia is at least partially mediated via the effects of the candidate genes and their combinations on relevant brain systems, resulting in alterations in different disorder domains, such as the cognitive deficits.

α-Synuclein pathology in very elderly Finns : A population-based clinico-neuropathologic and molecular genetic study of Dementia with Lewy bodies

Populations in developed countries are ageing fast. The elderly have the greatest incidence of de-mentia, and thus the increase in the number of demented individuals, increases the immediate costs for the governments concerning healthcare and hospital treatment. Attention is being paid to disorders behind cognitive impairment with behavioural and psychological symptoms, which are enormous contributors to the hospital care required for the elderly. The highest dreams are in prevention; however, before discovering the tools for preventing dementia, the pathogenesis behind dementia disorders needs to be understood. Dementia with Lewy bodies (DLB), a relatively recently discovered dementia disorder compared to Alzheimer’s disease (AD), is estimated to account for up to one third of primary degenerative dementia, thus being the second most common cause of dementia in the elderly. Nevertheless, the impact of neuropathological and genetic findings on the clinical syndrome of DLB is not fully established. In this present series of studies, the frequency of neuropathological findings of DLB and its relation to the clinical findings was evaluated in a cohort of subjects with primary degenerative dementia and in a population-based prospective cohort study of individuals aged 85 years or older. α-synuclein (αS) immunoreactive pathology classifiable according to the DLB consensus criteria was found in one fourth of the primary degenerative dementia subjects. In the population-based study, the corresponding figure was one third of the population, 38% of the demented and one fifth of the non-demented very elderly Finns. However, in spite of the frequent discovery of αS pathology, its association with the clinical symptoms was quite poor. Indeed, the common clinical features of DLB, hypokinesia and visual hallucinations, associated better with the severe neurofibrillary AD-type pathology than with the extensive (diffuse neocortical) αS pathology when both types of pathology were taken into account. The severity of the neurofibrillary AD-type pathology (Braak stage) associated with the extent of αS pathology in the brain. In addition, the genetic study showed an interaction between tau and αS; common variation in the αS gene (SNCA) associated significantly with the severity of the neurofibrillary AD-type pathology and nominally significantly with the extensive αS pathology. Further, the relevance and temporal course of the substantia nigra (SN) degeneration and of the spinal cord αS pathology were studied in relation to αS pathology in the brain. The linear association between the extent of αS pathology in the brain and the neuron loss in SN suggests that in DLB the degeneration of SN proceeds as the αS pathology extends from SN to the neocortex instead of early destruction of SN seen in Parkinson’s disease (PD). Furthermore, the extent of αS pathology in the brain associated with the severity of αS pathology in the thoracic and sacral autonomic nuclei of the spinal cord. The thoracic αS pathology was more common and more severe compared to sacral cord, suggesting that the progress of αS pathology proceeds downwards from the brainstem towards the sacral spinal cord.

Insights into the molecular genetics of celiac disease : Applying family- and population-based strategies

Celiac disease, or gluten intolerance, is triggered by dietary glutens in genetically susceptible individuals and it affects approximately 1% of the Caucasian population. The best known genetic risk factors for celiac disease are HLA DQ2 and DQ8 heterodimers, which are necessary for the development of the disease. However, they alone are not sufficient for disease induction, other risk factors are required. This thesis investigated genetic factors for celiac disease, concentrating on susceptibility loci on chromosomes 5q31-q33, 19p13 and 2q12 previously reported in genome-wide linkage and association studies. In addition, a novel genotyping method for the detection of HLA DQ2 and DQ8 coding haplotypes was validated. This study was conducted using Finnish and Hungarian family materials, and Finnish, Hungarian and Italian case-control materials. Genetic linkage and association were analysed in these materials using candidate gene and fine-mapping approaches. The results confirmed linkage to celiac disease on the chromosomal regions 5q31-q33 and 19p13. Fine-mapping on chromosome 5q31-q33 revealed several modest associations in the region, and highlighted the need for further investigations to locate the causal risk variants. The MYO9B gene on chromosome 19p13 showed evidence for linkage and association particularly with dermatitis herpetiformis, the skin manifestation of celiac disease. This implies a potential difference in the genetic background of the intestinal and skin forms of the disease, although studies on larger samplesets are required. The IL18RAP locus on chromosome 2q12, shown to be associated with celiac disease in a previous genome-wide association study and a subsequent follow-up, showed association in the Hungarian population in this study. The expression of IL18RAP was further investigated in small intestinal tissue and in peripheral blood mononuclear cells. The results showed that IL18RAP is expressed in the relevant tissues. Two putative isoforms of IL18RAP were detected by Western blot analysis, and the results suggested that the ratios and total levels of these isoforms may contribute to the aetiology of celiac disease. A novel genotyping method for celiac disease-associated HLA haplotypes was also validated in this thesis. The method utilises single-nucleotide polymorphisms tagging these HLA haplotypes with high sensitivity and specificity. Our results suggest that this method is transferable between populations, and it is suitable for large-scale analysis. In conclusion, this doctorate study provides an insight into the roles of the 5q31-q33, MYO9B, IL18RAP and HLA loci in the susceptibility to celiac disease in the Finnish, Hungarian and Italian populations, highlighting the need for further studies at these genetic loci and examination of the function of the candidate genes.

Weed management strategies for farming systems with herbicide tolerant cotton.

The introduction of glyphosate tolerant cotton has significantly improved the flexibility and management of a number of problem weeds in cotton systems. However, reliance on glyphosate poses risks to the industry in term of glyphosate resistance and species shift. The aims of this project were to identify these risks, and determine strategies to prevent and mitigate the potential for resistance evolution. Field surveys identified fleabane as the most common weed now in both irrigated and dryland system. Sowthistle has also increased in prevalence, and bladder ketmia and peachvine remained common. The continued reliance on glyphosate has favoured small seeded, and glyphosate tolerant species. Fleabane is both of these, with populations confirmed resistant in grains systems in Queensland and NSW. When species were assessed for their resistance risk, fleabane, liverseed grass, feathertop Rhodes grass, sowthistle and barnyard grass were determined to have high risk ratings. Management practices were also determined to rely heavily on glyphosate and therefore be high risk in summer fallows, and dryland glyphosate tolerant and conventional cotton. Situations were these high risk species are present in high risk cropping phases need particular attention. The confirmation of a glyphosate resistance barnyard grass population in a dryland glyphosate tolerant cotton system means resistance is now a reality for the cotton industry. However, experiments have shown that resistant populations can be managed with other herbicide options currently available. However, the options for fleabane management in cotton are still limited. Although some selective residual herbicides are showing promise, the majority of fleabane control tactics can only be used in other phases of the cotton rotation. An online glyphosate resistance tool has been developed. This tool allows growers to assess their individual glyphosate resistance risks, and how they can adjust their practices to reduce their risks. It also provides researchers with current information on weed species present and practices used across the industry. This tool will be extremely useful in tailoring future research and extension efforts. Simulations from the expanded glyphosate resistance model have shown that glyphosate resistance can be prevented and managed in glyphosate-tolerant cotton farming systems. However, for strategies to be successful, some effort is required. Simulations have shown the importance of controlling survivors of glyphosate applications, using effective glyphosate alternatives in fallows, and combining several effective glyphosate alternatives in crop, and these are the key to the prevention and management of glyphosate resistance.

Replication of the association of common rs9939609 variant of FTO with increased BMI in an Australian adult twin population but no evidence for gene by environment (G x E) interaction

OBJECTIVE: To further investigate a common variant (rs9939609) in the fat mass- and obesity-associated gene (FTO), which recent genome-wide association studies have shown to be associated with body mass index (BMI) and obesity. DESIGN: We examined the effect of this FTO variant on BMI in 3353 Australian adult male and female twins. RESULTS: The minor A allele of rs9939609 was associated with an increased BMI (P=0.0007). Each additional copy of the A allele was associated with a mean BMI increase of approximately 1.04 kg/m(2) (approximately 3.71 kg). Using variance components decomposition, we estimate that this single-nucleotide polymorphism accounts for approximately 3% of the genetic variance in BMI in our sample (approximately 2% of the total variance). By comparing intrapair variances of monozygotic twins of different genotypes we were able to perform a direct test of gene by environment (G x E) interaction in both sexes and gene by parity (G x P) interaction in women, but no evidence was found for either. CONCLUSIONS: In addition to supporting earlier findings that the rs9939609 variant in the FTO gene is associated with an increased BMI, our results indicate that the associated genetic effect does not interact with environment or parity.

Genetic Heterogeneity in Autism Spectrum Disorders in a Population Isolate

Positional cloning has enabled hypothesis-free, genome-wide scans for genetic factors contributing to disorders or traits. Traditionally linkage analysis has been used to identify regions of interest, followed by meticulous fine mapping and candidate gene screening using association methods and finally sequencing of regions of interest. More recently, genome-wide association analysis has enabled a more direct approach to identify specific genetic variants explaining a part of the variance of the phenotype of interest. Autism spectrum disorders (ASDs) are a group of childhood onset neuropsychiatric disorders with shared core symptoms but varying severity. Although a strong genetic component has been established in ASDs, genetic susceptibility factors have largely eluded characterization. Here, we have utilized modern molecular genetic methods combined with the advantages provided by the special population structure in Finland to identify genetic risk factors for ASDs. The results of this study show that numerous genetic risk factors exist for ASDs even within a population isolate. Stratification based on clinical phenotype resulted in encouraging results, as previously identified linkage to 3p14-p24 was replicated in an independent family set of families with Asperger syndrome, but no other ASDs. Fine-mapping of the previously identified linkage peak for ASDs at 3q25-q27 revealed association between autism and a subunit of the 5-hydroxytryptamine receptor 3C (HTR3C). We also used dense, genome-wide single nucleotide polymorphism (SNP) data to characterize the population structure of Finns. We observed significant population substructure which correlates with the known history of multiple consecutive bottle-necks experienced by the Finnish population. We used this information to ascertain a genetically homogenous subset of autism families to identify possible rare, enriched risk variants using genome-wide SNP data. No rare enriched genetic risk factors were identified in this dataset, although a subset of families could be genealogically linked to form two extended pedigrees. The lack of founder mutations in this isolated population suggests that the majority of genetic risk factors are rare, de novo mutations unique to individual nuclear families. The results of this study are consistent with others in the field. The underlying genetic architecture for this group of disorders appears highly heterogeneous, with common variants accounting for only a subset of genetic risk. The majority of identified risk factors have turned out to be exceedingly rare, and only explain a subset of the genetic risk in the general population in spite of their high penetrance within individual families. The results of this study, together with other results obtained in this field, indicate that family specific linkage, homozygosity mapping and resequencing efforts are needed to identify these rare genetic risk factors.

Helicobacter pylori in Vammala, Finland: seroepidemiological studies and a population-based ‘screen-and-treat’ programme

Helicobacter pylorin (helikobakteeri) tartunta saadaan yleensä lapsena ja tauti jää tavallisesti pysyväksi ilman täsmähoitoa. Onnistunut hoito parantaa pysyvästi helikobakteerista aiheutuvan mahan haavataudin ja näyttää ehkäisevän mahalaukun pahanlaatuisten muutosten kehittymistä. Aloitimme Vammalassa terveyskeskuksessa toteutetun kansainvälisesti ainutlaatuisen väestöpohjaisen helikobakteeritulehduksen seulonta- ja hoito-ohjelman pilottitutkimuksella 1994. 1996 kaikki 15-40-vuotiaat ja 1997-2000 15- ja 45-vuotiaat vammalalaiset kutsuttiin verinäyteseulontaan. Yhteensä 4626 henkilöä (75% kutsutuista) osallistui seulontaan. Vasta-ainepositiivisille tarjottiin helikobakteeritulehduksen lopettava lääkekuuri. Toiminnan seurauksena helikobakteeritulehduksen esiintyvyyden laskettiin vähentyneen 12%:sta 4%:iin 15-40-vuotiaiden ikäryhmässä. Tutkimme myös helikobakteerivasta-ainepositiivisten ja -negatiivisten eroja sekä helikobakteeritulehduksen riskitekijöitä kyselytutkimuksella. Lapsuudenkodin asumisahtauden, äidin matalan koulutusasteen, tupakoinnin, alkoholinkäytön, huonojen asunto-olojen ja ylävatsavaivoista johtuvien sairauslomien todettiin liittyvän helikobakteeritulehdukseen monimuuttuja-analyysissa. Tutkimme seulontaohjelmassa käyttämiemme IgG- ja IgA-luokan helikobakteeri-vasta-ainetestien luotettavuutta eri ikäryhmissä ottaen huomioon atrofisen gastriitin esiintyvyyden. 561 kliinisin perustein gastroskopoidun potilaan aineistossa IgG-testi osoittautui erittäin herkäksi kaikissa ikäryhmissä (99%). Tarkkuus oli myös vanhemmissa ikäryhmissä hyvä (97-93%), kun atrofista gastriittia sairastavat suljettiin pois. IgA- ja CagA-helikobakteerivasta-aineiden on todettu liittyvän lisääntyneeseen mahahaava- ja mahasyöpäriskiin. Analysoimme 560 henkilön pariseeruminäytteet, jotka oli otettu kahden vuosikymmenen välein, ja totesimme, että IgA-vasta-aineiden esiintyvyyden lisääntyyminen iän myötä johtuu paitsi syntymäajankohdasta ja uusista infektioista myös IgA-vasta-ainetasojen kohoamisesta helikobakteeritulehduksen aikana. Selvitimme myös CagA-vasta-ainetasojen muuttumista analysoimalla seeruminäytteet, jotka oli otettu kahden vuosikymmenen välein. Totesimme, että samanaikaisesti kun helikobakteerin esiintyvyys väestössä on alentunut, erityisesti CagA-positiiviset infektiot ovat vähentyneet. Tutkimuksemme osoittaa, että Suomessa terveyskeskuksen yhteydessä voidaan toteuttaa näin laajamittainen seulonta- ja hoito-ohjelma, johon suomalaiset osallistuvat aktiivisesti. Nähtäväksi jää, kuinka paljon ohjelma kykeni vähentämään helikobakteeritulehdukseen liittyviä myöhäisseuraamuksia.

Is prosopis a curse or a blessing? : An ecological economic analysis of an invasive alien tree species in Sudan.

The issue of the usefulness of different prosopis species versus their status as weeds is a matter of hot debate around the world. The tree Prosopis juliflora had until 2000 been proclaimed weedy in its native range in South America and elsewhere in the dry tropics. P. juliflora or mesquite has a 90-year history in Sudan. During the early 1990s a popular opinion in central Sudan and the Sudanese Government had begun to consider prosopis a noxious weed and a problematic tree species due to its aggressive ability to invade farmlands and pastures, especially in and around irrigated agricultural lands. As a consequence prosopis was officially declared an invasive alien species also in Sudan, and in 1995 a presidential decree for its eradication was issued. Using a total economic valuation (TEV) approach, this study analysed the impacts of prosopis on the local livelihoods in two contrasting irrigated agricultural schemes. Primarily a problem-based approach was used in which the derivation of non-market values was captured using ecological economic tools. In the New Halfa Irrigation Scheme in Kassala State, four separate household surveys were conducted due to diversity between the respective population groups. The main aim was here to study the magnitude of environmental economic benefits and costs derived from the invasion of prosopis in a large agricultural irrigation scheme on clay soil. Another study site, the Gandato Irrigation Scheme in River Nile State represented impacts from prosopis that an irrigation scheme was confronted with on sandy soil in the arid and semi-arid ecozones along the main River Nile. The two cases showed distinctly different effects of prosopis but both indicated the benefits to exceed the costs. The valuation on clay soil in New Halfa identified a benefit/cost ratio of 2.1, while this indicator equalled 46 on the sandy soils of Gandato. The valuation results were site-specific and based on local market prices. The most important beneficial impacts of prosopis on local livelihoods were derived from free-grazing forage for livestock, environmental conservation of the native vegetation, wood and non-wood forest products, as well as shelterbelt effects. The main social costs from prosopis were derived from weeding and clearing it from farm lands and from canalsides, from thorn injuries to humans and livestock, as well as from repair expenses vehicle tyre punctures. Of the population groups, the tenants faced most of the detrimental impacts, while the landless population groups (originating from western and eastern Sudan) as well as the nomads were highly dependent on this tree resource. For the Gandato site the monetized benefit-cost ratio of 46 still excluded several additional beneficial impacts of prosopis in the area that were difficult to quantify and monetize credibly. In River Nile State the beneficial impact could thus be seen as completely outweighing the costs of prosopis. The results can contributed to the formulation of national and local forest and agricultural policies related to prosopis in Sudan and also be used in other countries faced with similar impacts caused by this tree.

Multiple host use by a sap-sucking membracid: population consequences of nymphal development on primary and secondary host plant species

Aconophora compressa is a gregarious, sap-sucking insect that uses multiple host plant species. Nymphal host plant species (and variety) significantly affected nymphal survival, nymphal development rate and the subsequent size and fecundity of adults, with fiddlewood ( Citharexylum spinosum ) being significantly best in all respects. Nymphs that developed on a relatively poor host ( Duranta erecta var “geisha girl”) and which were moved to fiddlewood as adults laid significantly fewer eggs (mean ± SE = 836 ± 130) than those that developed solely on fiddlewood (1,329 ± 105). Adults on geisha girl, regardless of having been reared as nymphs on fiddlewood or geisha girl, laid significantly fewer eggs (342 ± 83 and 317 ± 74, respectively) than adults on fiddlewood. A simple model that incorporates host plant related survival, development rate and fecundity suggests that the population dynamics of A. compressa are governed mainly by fiddlewood, the primary host. The results have general implications for understanding the population dynamics of herbivores that use multiple host plant species, and also for the way in which weed biological control host testing methods should be conducted.

Raw data for "Linkage disequilibrium estimation of effective population size with immigrants from divergent populations: a case study on Spanish mackerel (Scomberomorus commerson)."

Abstract of Macbeth, G. M., Broderick, D., Buckworth, R. & Ovenden, J. R. (In press, Feb 2013). Linkage disequilibrium estimation of effective population size with immigrants from divergent populations: a case study on Spanish mackerel (Scomberomorus commerson). G3: Genes, Genomes and Genetics. Estimates of genetic effective population size (Ne) using molecular markers are a potentially useful tool for the management of endangered through to commercial species. But, pitfalls are predicted when the effective size is large, as estimates require large numbers of samples from wild populations for statistical validity. Our simulations showed that linkage disequilibrium estimates of Ne up to 10,000 with finite confidence limits can be achieved with sample sizes around 5000. This was deduced from empirical allele frequencies of seven polymorphic microsatellite loci in a commercially harvested fisheries species, the narrow barred Spanish mackerel (Scomberomorus commerson). As expected, the smallest standard deviation of Ne estimates occurred when low frequency alleles were excluded. Additional simulations indicated that the linkage disequilibrium method was sensitive to small numbers of genotypes from cryptic species or conspecific immigrants. A correspondence analysis algorithm was developed to detect and remove outlier genotypes that could possibly be inadvertently sampled from cryptic species or non-breeding immigrants from genetically separate populations. Simulations demonstrated the value of this approach in Spanish mackerel data. When putative immigrants were removed from the empirical data, 95% of the Ne estimates from jacknife resampling were above 24,000.