Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and... Show moreDifferences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes. Show less
Lambers, L.; Faßbinder, J.W.E.; Campbell, S.; Hauser, S. 2019
The ancient city of Charax Spasinou was situated in southern Iraq near Basra, between the rivers Tigris and Eulaios, at the modern location Jebel Khayaber. It offers the opportunity to study the... Show moreThe ancient city of Charax Spasinou was situated in southern Iraq near Basra, between the rivers Tigris and Eulaios, at the modern location Jebel Khayaber. It offers the opportunity to study the layout and functionality of a major urban city dating from the Seleucid to the Sasanian period. The city was originally founded by Alexander the Great and given the name Alexandria (Campbell et al. 2019: 215). After its destruction by flooding, it was re-founded in BC 166/165 by the Seleucid king Antiochos IV and re-named Antiochia. This settlement was again destroyed by flooding. It was rebuilt under Hyspaosines and named Charax Spasinou (ancient Greek for ‘palisade of [Hy]spa[o]sines’). Due to its favourable location Charax became a very important harbour in the Persian Gulf area and a major trading point between India and Babylonia, supplying goods further up to the Mediterranean (Campbell et al. 2019). Charax was first identified with Jebel Khayaber in 1965, when distinctive ramparts with an average height of 4m to 6m were documented (Hansman 1967: 39). In 2016 Jane Moon, Robert Killick and Stuart Campbell (University of Manchester), together with Stefan Hauser (University of Konstanz) and the Iraqi State Board for Antiquities & Heritage, started a project to document and protect the ancient city of Charax Spasinou. The aim is to investigate the site through an integration of remote sensing technologies and surface survey as well as limited excavations in order to reconstruct the city layout, its chronology and to document its state of preservation for purposes of conservation and site management. Show less
Huffman, J.E.; Albrecht, E.; Teumer, A.; Mangino, M.; Kapur, K.; Johnson, T.; ... ; Vitart, V. 2015
Background-Fibrin fragment D-dimer, one of several peptides produced when crosslinked fibrin is degraded by plasmin, is the most widely used clinical marker of activated blood coagulation. To... Show moreBackground-Fibrin fragment D-dimer, one of several peptides produced when crosslinked fibrin is degraded by plasmin, is the most widely used clinical marker of activated blood coagulation. To identity genetic loci influencing D-dimer levels, we performed the first large-scale, genome-wide association search. Methods and Results-A genome-wide investigation of the genomic correlates of plasma D-dimer levels was conducted among 21 052 European-ancestry adults. Plasma levels of D-dimer were measured independently in each of 13 cohorts. Each study analyzed the association between approximate to 2.6 million genotyped and imputed variants across the 22 autosomal chromosomes and natural-log-transformed D-dimer levels using linear regression in additive genetic models adjusted for age and sex. Among all variants, 74 exceeded the genome-wide significance threshold and marked 3 regions. At 1p22, rs12029080 (P=6.4 x 10(-52)) was 46.0 kb upstream from F3, coagulation factor III (tissue factor). At 1q24, rs6687813 (P=2.4x10(-14)) was 79.7 kb downstream of F5, coagulation factor V. At 4q32, rs13109457 (P=2.9x10(-18)) was located between 2 fibrinogen genes: 10.4 kb downstream from FGG and 3.0 kb upstream from FGA. Variants were associated with a 0.099-, 0.096-, and 0.061-unit difference, respectively, in natural-log-transformed D-dimer and together accounted for 1.8% of the total variance. When adjusted for nonsynonymous substitutions in F5 and FGA loci known to be associated with D-dimer levels, there was no evidence of an additional association at either locus. Conclusions-Three genes were associated with fibrin D-dimer levels. Of these 3, the F3 association was the strongest, and has not been previously reported. (Circulation. 2011;123:1864-1872.) Show less
