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

PALVELUTUOTTEEN HINNOITTELUN KEHITTÄMINEN

Tämän opinnäytetyön aiheena on palvelutuotteen hinnoittelun kehittäminen. Tutkimuksen kohteena on Tili- ja isännöitsijätoimisto Ky. Tili- ja isännöitsijätoimisto Ky on Vaasassa toimiva tili- ja isännöintitoimisto, joka tarjoaa taloushallinto- ja isännöintipalveluita yrityksille. Tutkimuksen tavoitteena on kehittää Tili- ja isännöitsijätoimisto Ky:n isännöitsijän palvelutuotteiden hinnoittelua. Hinnoittelumenetelmäksi valittiin toimintoperusteinen hinnoittelu, jonka lähtökohtana on selvittää asiakaskohtaisia välillisiä kustannuksia. Kysymys oli suorite-kohtaisten kustannusten laskemisesta, eli toimintoperusteisesta prosessilaskennasta. Toimintoperusteinen prosessilaskenta tukee hinnoittelun päätöstä. Toiminto-analyysin jälkeen selvitettiin resurssien kohdistumista yrityksen eri toiminnoille. Aluksi selvitettiin yrityksen kustannusajuri, jonka perusteella kustannukset on kohdistettu eri toiminnoille. Seuraavaksi selvitettiin toimintoajurin avulla toimintoihin liittyvät yksikkökustannukset. Tuotteiden hinnoittelussa myyntihinnan on tarkoituksena sisältää kaikkien kustannusten lisäksi voittotavoite. Tutkimuksen teoriaosuuden keskeisiä asioita ovat toimintoperusteisen kustannuslaskennan, sekä hinnoittelun perusteiden esittely. Niiden avulla voidaan perustella hinnoittelupäätöstä tukeva toimintolaskenta. Opinnäytetyössä esitellään lisäksi kustannusperusteista hinnoittelua sekä isännöintiä ja tilitoimistoa yleisesti. Tutkimusmenetelmänä käytettiin kvalitatiivista eli laadullista tutkimusta. Tutkimuksen teoriaosuuteen käytettiin toimintolaskennan, taloushallinnon alan sekä hinnoittelun teoriaan liittyvää kirjallisuutta. Aineistonkeruussa havainnoitiin yrityksen tilinpäätöstä vuodelta 2016 ja yrityksen toimintaa liittyviä ohjelmia sekä tietokantoja. Lisäksi haastateltiin Tili- ja isännöitsijätoimisto Ky:n omistajaa ja työntekijöitä.This research was designed to develop the used pricing method for the case firm Tili- ja isännöitsijätoimisto Ky. The main area of this research focused on the main service products in property management. The case firm offers financial accounting and management services to house companies and other customer companies. Activity based costing was selected as the new pricing method in order to identify the customer-specific indirect costs. The aim of activity-based costing was to support pricing decisions for the case firm. In the implementation steps, activities must be identified first, and then the process continues with an activity analysis. Once the costs of activity and its drivers have been identified and its costs have been determined, then the costs of activity is allocated to the service product. In the allocation process, when the activity driver has been determined, the cost per unit can then be determined. Once the product cost per unit has been determined then the case firm considers the generated value of its service product, so the pricing of all the service product sales cover the fixed expenses with any remaining contribution margin providing profits. The theoretical study of this thesis introduced activity based costing and pricing to support activity based cost implementation and pricing decisions. In addition, it introduced cost based pricing and property management business and accounting firms in general. This research was implemented using the qualitative research method. The research material consists of related activity based costing, financial management, management accounting and pricing literature. The theoretical information was gathered from scientific research, academic books and some material was collect-ed from the Internet. The empirical data in this research was gathered by observing the case company’s financial statement from the year 2016 together with some business activities related programs and databases. In addition, was collected by interviewing the case company owner and the other employers of the company

Common genetic variants influence human subcortical brain structures

The highly complex structure of the human brain is strongly shaped by genetic influences1. Subcortical brain regions form circuits with cortical areas to coordinate movement2, learning, memory3 and motivation4, and altered circuits can lead to abnormal behaviour and disease2. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume5 and intracranial volume6. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10−33; 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction

Common genetic variants influence human subcortical brain structures

The highly complex structure of the human brain is strongly shaped by genetic influences1. Subcortical brain regions form circuits with cortical areas to coordinate movement2, learning, memory3 and motivation4, and altered circuits can lead to abnormal behaviour and disease2. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume5 and intracranial volume6. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10−33; 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction