Björned – benanalyser och kulturhistoriska tolkningar: Undersökningar kring en nordsvensk begravningsplats från tidig medeltid

Björned – bone analysis and historical interpretations. Investigations of an early medieval burial place in northern Sweden By Leif Grundberg, Anders Götherström and Barbro Hårding In the small village called Björned in Torsåker parish, in the county of Ångermanland in northern Sweden, an early medieval cemetery was investigated. The investigation forms part of the Styresholm project, which involves the study of the area adjoining the lower part of the Ångermanälven river during the Middle Ages and the Iron Age. The Björned cemetery measures only c. 25×12 m. It is not mentioned in historical sources and nothing above the surface reveals that this is a cemetery. During the excavation more than fifty graves were identified, which all followed Christian burial customs. 14Canalyses of human bones suggest that the cemetery was used from the 10th century until the 13th century, although an adjoining settlement existed from the early Iron Age. Most of the bone material from the graves is well preserved and suitable for scientific investigation. The present study has been directed towards problems connected with the change of religion, the parish organisation, the family structure, the social organisation, and the power structures. These are topics that arise when the results from the excavation are compared with other ancient remains, existing churches, placenames and the topography of the region. The article presents the research in progress, including molecular analyses and studies of epigenetic traits. One of the main questions dealt with is whether Björned was a family cemetery. The anthropological analyses suggest that several individuals are closely related. This theory is supported by the molecular analyses. A Y-chromosomal short tandem repeat, DYS388, was extracted and amplified from some individuals from Björned. Alleles could be identified in six individuals. The composition of the alleles was such that the individuals could not be regarded as a sample of a Swedish population in a genetic sense. More likely they represent a sample drawn from a Same population or a Swedish family with a Same element. A short introduction is also given to further investigations that have started recently, including comparative studies of the Viking Age cemeteries at Björkå and Holm in Överlännäs parish. The importance of relating the results with a local and regional historical context is stressed in the article, which also deals with the early Christianisation, the Same influence and gender perspectives. Using medieval churches, Viking Age silver-hoards, and rich chamber-women graves as the point of departure, it is argued that Björned was situated in a settlement area of central importance. The centrality is thought to have been based on transit exchange and transport of products from the interior of Norrland

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Genomic correlates of glatiramer acetate adverse cardiovascular effects lead to a novel locus mediating coronary risk

Glatiramer acetate is used therapeutically in multiple sclerosis but also known for adverse effects including elevated coronary artery disease (CAD) risk. The mechanisms underlying the cardiovascular side effects of the medication are unclear. Here, we made use of the chromosomal variation in the genes that are known to be affected by glatiramer treatment. Focusing on genes and gene products reported by drug-gene interaction database to interact with glatiramer acetate we explored a large meta-analysis on CAD genome-wide association studies aiming firstly, to investigate whether variants in these genes also affect cardiovascular risk and secondly, to identify new CAD risk genes. We traced association signals in a 200-kb region around genomic positions of genes interacting with glatiramer in up to 60 801 CAD cases and 123 504 controls. We validated the identified association in additional 21 934 CAD cases and 76 087 controls. We identified three new CAD risk alleles within the TGFB1 region on chromosome 19 that independently affect CAD risk. The lead SNP rs12459996 was genome-wide significantly associated with CAD in the extended meta-analysis (odds ratio 1.09, p = 1.58×10-12). The other two SNPs at the locus were not in linkage disequilibrium with the lead SNP and by a conditional analysis showed p-values of 4.05 × 10-10 and 2.21 × 10-6. Thus, studying genes reported to interact with glatiramer acetate we identified genetic variants that concordantly with the drug increase the risk of CAD. Of these, TGFB1 displayed signal for association. Indeed, the gene has been associated with CAD previously in both in vivo and in vitro studies. Here we establish genome-wide significant association with CAD in large human samples.This work was supported by grants from the Fondation Leducq (CADgenomics: Understanding CAD Genes, 12CVD02), the German Federal Ministry of Education and Research (BMBF) within the framework of the e:Med research and funding concept (e:AtheroSysMed, grant 01ZX1313A-2014 and SysInflame, grant 01ZX1306A), and the European Union Seventh Framework Programme FP7/2007-2013 under grant agreement no HEALTH-F2-2013-601456 (CVgenes-at-target). Further grants were received from the DFG as part of the Sonderforschungsbereich CRC 1123 (B2). T.K. was supported by a DZHK Rotation Grant. I.B. was supported by the Deutsche Forschungsgemeinschaft (DFG) cluster of excellence ‘Inflammation at Interfaces’. F.W.A. is supported by a Dekker scholarship-Junior Staff Member 2014T001 - Netherlands Heart Foundation and UCL Hospitals NIHR Biomedical Research Centre

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

Medeltid i centrum : europeisering, historieskrivning och kulturarvsbruk i norrländska kulturmiljöer

This thesis aims to shed light upon three related research areas with the medieval period at their core: medieval Europeanization, the historiography of medieval places, the importance of the cultural environment and medieval period for the present day. By these means several current research angles are integrated within medieval research, the history of science and cultural heritage research. Six investigations of medieval central places in Ångermanland and Medelpad in northern Sweden are used to exemplify these issues. The use of hermeneutic theory emphasises the relationship between the present day community, the individual and the interpretation of history. The sites presented in the thesis represent the entire medieval period from the 11th Century to the start of the 16th Century. Two of them – Kvissle chapel and “Skelettåkern” (=The Skeleton Field) in Björned – functioned as private Christian churches or graveyards; two were important harbours – Sankt Olofshamn (=Saint Olof’s Harbour) and Kyrkesviken (=Church bay); two functioned as military castles or fortifications – Styresholm/ ”Pukeborg” and Bjärtrå stronghold. In addition to these, four medieval stone parish churches have been examined: the old church at Alnö in Medelpad, and the churches of Torsåker, Boteå and Grundsunda in Ångermanland. The Europeanization of Norrland is discussed with reference to aspects such as religious transition and parish formation, monetarization and changes in household structure, trade specialization and administrative territorialization. Central places have played an important role in this process. Historiography illuminates how, and in which contexts, knowledge and understanding of history and medieval central places has developed and been communicated. This includes the use of place names and the oral narration of history, authorship and scientific research into local history. A number of primary school teachers, adult education college (‘folk high school’) teachers and priests were particularly important for the growth of local historical research around the turn of the 20th century. The use of cultural heritage is illustrated with a discussion of how the medieval cultural environments in Ångermanland and Medelpad have been interpreted and used in recent years. This includes aspects such as signposting, teaching and research activities, mass media attention, amateur history plays and similar performances, and the formation of various types of society. These three aspects of Norrland’s medieval period, together with the use of a cultural heritage perspective, form a broader holistic picture of the social role of scientific research and the cultural environment, where local interest in history is important for regional development

Den medeltida hamnen : maktfaktorer i norrländsk samhällsutveckling

Studier kring hamnarnas ekonomiska och administrativa betydelse för samhällsutvecklingen har hittills dominerat forskningen. Arkeologiska undersökningar av medeltida hamnlokaler i Norrlands kustområde har lyft fram ytterligare en intressant aspekt: hamnen som tidigt uttryck för en medveten centralortsbildning

Den medeltida hamnen : maktfaktorer i norrländsk samhällsutveckling

Studier kring hamnarnas ekonomiska och administrativa betydelse för samhällsutvecklingen har hittills dominerat forskningen. Arkeologiska undersökningar av medeltida hamnlokaler i Norrlands kustområde har lyft fram ytterligare en intressant aspekt: hamnen som tidigt uttryck för en medveten centralortsbildning