Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation.

Thyroid dysfunction is an important public health problem, which affects 10% of the general population and increases the risk of cardiovascular morbidity and mortality. Many aspects of thyroid hormone regulation have only partly been elucidated, including its transport, metabolism, and genetic determinants. Here we report a large meta-analysis of genome-wide association studies for thyroid function and dysfunction, testing 8 million genetic variants in up to 72,167 individuals. One-hundred-and-nine independent genetic variants are associated with these traits. A genetic risk score, calculated to assess their combined effects on clinical end points, shows significant associations with increased risk of both overt (Graves' disease) and subclinical thyroid disease, as well as clinical complications. By functional follow-up on selected signals, we identify a novel thyroid hormone transporter (SLC17A4) and a metabolizing enzyme (AADAT). Together, these results provide new knowledge about thyroid hormone physiology and disease, opening new possibilities for therapeutic targets

Genome-wide analysis identifies 12 loci influencing human reproductive behavior.

The genetic architecture of human reproductive behavior-age at first birth (AFB) and number of children ever born (NEB)-has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Genetic architecture of subcortical brain structures in 38,851 individuals

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease

Novel genetic loci underlying human intracranial volume identified through genome-wide association

Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five novel loci for intracranial volume and confirmed two known signals. Four of the loci are also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic=0.748), which indicated a similar genetic background and allowed for the identification of four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, Parkinson’s disease, and enriched near genes involved in growth pathways including PI3K–AKT signaling. These findings identify biological underpinnings of intracranial volume and provide genetic support for theories on brain reserve and brain overgrowth

Abschlussbericht zum Projekt "Ressourcenschonende Mischschweißverbindungen für Hochleistungs-Leichtbauverbunde"

Im Rahmen des Projektes wurde das Rührreibschweißen als ressourceneffizientes und umweltfreundliches Fertigungsverfahren zur Herstellung von beanspruchungs- und gewichtsoptimierten Automobilbauteilen erforscht. Dabei galt es, Aluminium und Stahl in verschiedenen Dicken durch Rührreibschweißen zu fügen und durch anschließendes Umformen zum End- bzw. Zwischenprodukt umzuformen. Die auf die Festigkeiten der Werkstoffe angepassten Blechdicken führen zu einer optimalen Ausnutzung der Werkstoffe, da an jeder Stelle der Werkstoff verwendet werden kann, der die lokalen Anforderungen am besten erfüllt. Durch den Einsatz dieser sogenannten Tailor Welded Blanks sinkt der Werkstoffverbrauch insgesamt und es können auf Leichtbau optimierte Bauteile hergestellt werden. Im Rahmen des Projektes wurden verschiedene Aluminium- und Stahlgüten in unterschiedlichen Dicken durch Rührreibschweißen gefügt und die Festigkeits- sowie Umformeigenschaften ermittelt. Da die Einhaltung von engen Toleranzen mit hohen Kosten in der Fertigung einhergeht, wurden die für den Prozess notwendigen Toleranzen untersucht, Lösungen zum Umgang mit diesen Toleranzen erarbeitet und Anforderungen an Anlagen zur Produktion von Tailor Welded Blanks identifiziert. Zudem wurde das Umformen von Blechen mit unterschiedlichen Materialen und Blechdicken untersucht. Darüber hinaus wurde eine Reihe weiterer Themen wie das Verschweißen von Gusswerkstoffen und Wärmebehandlungsstrategien beleuchtet. Abschließend wurden Demonstratorbauteile in Form von Tailor Welded Blanks in Aluminium-Stahl- Mischbauweise durch Rührreibschweißen und anschließendes Umformen gefertigt

Mean scores of homocysteine levels for all patients, restenosis group, and comparative group

<p><b>Copyright information:</b></p><p>Taken from "Hyperhomocysteinemia and recurrent carotid stenosis"</p><p>http://www.biomedcentral.com/1471-2261/8/1</p><p>BMC Cardiovascular Disorders 2008;8():1-1.</p><p>Published online 17 Jan 2008</p><p>PMCID:PMC2245907.</p><p></p