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

The genetic architecture of the human cerebral cortex

INTRODUCTION The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure. RATIONALE To identify genetic variants associated with human cortical structure at both global and regional levels, we conducted a genome-wide association meta-analysis of brain MRI data from 51,665 individuals across 60 cohorts. We analyzed the surface area and average thickness of the whole cortex and 34 cortical regions with known functional specializations. RESULTS We identified 306 nominally genome-wide significant loci (P < 5 × 10−8) associated with cortical structure in a discovery sample of 33,992 participants of European ancestry. Of the 299 loci for which replication data were available, 241 loci influencing surface area and 14 influencing thickness remained significant after replication, with 199 loci passing multiple testing correction (P < 8.3 × 10−10; 187 influencing surface area and 12 influencing thickness). Common genetic variants explained 34% (SE = 3%) of the variation in total surface area and 26% (SE = 2%) in average thickness; surface area and thickness showed a negative genetic correlation (rG = −0.32, SE = 0.05, P = 6.5 × 10−12), which suggests that genetic influences have opposing effects on surface area and thickness. Bioinformatic analyses showed that total surface area is influenced by genetic variants that alter gene regulatory activity in neural progenitor cells during fetal development. By contrast, average thickness is influenced by active regulatory elements in adult brain samples, which may reflect processes that occur after mid-fetal development, such as myelination, branching, or pruning. When considered together, these results support the radial unit hypothesis that different developmental mechanisms promote surface area expansion and increases in thickness. To identify specific genetic influences on individual cortical regions, we controlled for global measures (total surface area or average thickness) in the regional analyses. After multiple testing correction, we identified 175 loci that influence regional surface area and 10 that influence regional thickness. Loci that affect regional surface area cluster near genes involved in the Wnt signaling pathway, which is known to influence areal identity. We observed significant positive genetic correlations and evidence of bidirectional causation of total surface area with both general cognitive functioning and educational attainment. We found additional positive genetic correlations between total surface area and Parkinson’s disease but did not find evidence of causation. Negative genetic correlations were evident between total surface area and insomnia, attention deficit hyperactivity disorder, depressive symptoms, major depressive disorder, and neuroticism. CONCLUSION This large-scale collaborative work enhances our understanding of the genetic architecture of the human cerebral cortex and its regional patterning. The highly polygenic architecture of the cortex suggests that distinct genes are involved in the development of specific cortical areas. Moreover, we find evidence that brain structure is a key phenotype along the causal pathway that leads from genetic variation to differences in general cognitive function

Validity And Reliability Study Of Turkish Version Of “Muscle Dysmorphic Disorder Inventory” And “Bodybuilder Image Grid” Scales

Background: Although bigorexia symptoms are rapidly increasing, it is mostly an under recognized condition in Turkish male bodybuilders. There are no validated screening tools to identify the symptoms. Objective: The purpose of this study is to evaluate the validity of the Turkish version of the MDDI and the BIG towards the diagnosis of bigorexia and to provide health care professionals with early screening tools. Methods: One hundred twenty male bodybuilders, fifty-eight professional bodybuilders and six tytwo recreational bodybuilders, all of whom matched the research criteria, were included in this study. MDDI and BIG forms were filled by the bodybuilders, along with an “Individual Characteristic Information Form”, a “Nutrition-related Information Form”, and a “Bodybuilding-related Information Form”. To evaluate the construct validity, factor analysis was conducted and resulted in a three factor construct. Results: The factor-loading values ranged from 0.542- 0.827. Calculations of Cronbach’s alpha for the MDDI sum (α = 0.657) revealed a good internal consistency. The MDDI, BIG O, and BIG S intra class correlation coefficients (ICC) were found to be 0.840, 0.908, and 0.879, respectively. As a result, MDDI had acceptable reliability and that of BIG O and BIG S was excellent. Discussion: Turkish MDDI, BIG-O and BIG-S forms proved to be valid and reliable scales and were adequate for determining the symptoms of bigo rexia in male bodybuilders. Using these forms, there was a statistically significant relationship between bigorexia and eating disorders, which were significantly positively correlated. Conclusion: Our results support the feasibility of using the MDDI, the BIG-O, and the BIG-S forms to determine symptoms of bigorexia in Turkish population. Further studies are needed to confirm if this result can be generalized to female bodybuilders. © 2019 Bentham Science Publishers.Scopu

Perfil de ácidos graxos do leite de vacas alimentadas com óleo de soja e monensina no início da lactação Milk fatty acid profile of cows fed monensin and soybean oil in early lactation

Avaliaram-se os efeitos da adição de monensina sódica combinada com óleo de soja na dieta de vacas lactantes sobre o perfil de ácidos graxos (AG) do leite na 5ª e 15ª semanas da lactação. Foram utilizadas 16 vacas multíparas cruzadas, dispostas em delineamento em blocos casualizados, em um arranjo fatorial 2 x 2 (presença ou não de monensina e presença ou não de óleo de soja). Os tratamentos consistiram das dietas: CT (controle) = sem monensina ou óleo; MN = 33 ppm de monensina; OL = 3,9% de óleo de soja; e OM = óleo e monensina. Os animais foram confinados e alimentados com 52% de silagem de milho e 48% de concentrado. Não foi verificada interação entre óleo de soja e monensina para os ácidos graxos avaliados. A monensina aumentou os AG insaturados, monoinsaturados e poliinsaturados em 9,0; 8,8; e 10,7%, respectivamente. O óleo apresentou maior impacto sobre os AG poliinsaturados, aumentando-os em 39,2; 39,3; e 24,2%, respectivamente. Também reduziu os AG de cadeias curta (43,7%) e média (49,1%) e aumentou os AG de cadeia longa (55,3%). Os isômeros trans-C18:1 foram aumentados tanto pelo óleo como pela monensina, indicando efeito aditivo para trans-10 C18:1, que foi negativamente correlacionado ao teor de gordura do leite. O isômero cis-9 trans-11 do ácido linoléico conjugado (CLA) não foi influenciado pelos tratamentos, observando-se que o óleo reduziu a atividade da delta9-desaturase. Houve interação entre tratamentos e semana da lactação sobre os AG de cadeias curta e média, C14:0, C16:0, cis-9 C18:1 e trans-10 C18:1. Os maiores efeitos sobre o perfil de AG do leite foram registrados quando monensina e óleo foram fornecidos em conjunto na dieta de vacas lactantes.<br>The objective of this trial was to evaluate the effects of dietary monensin and soybean oil on milk fatty acid (FA) profile in the 5th and 15th week of lactation of dairy cows. Sixteen multiparous crossbred dairy cows averaging 30 days in milk were assigned to a completely randomized block design in a 2 x 2 factorial arrangement (presence or absence of monensin and soybean oil). The following diets were used: control not supplemented with monensin or soybean oil (CT), 33 ppm of monensin (MN), 3.9% of soybean oil (OL) or a combination of soybean oil plus monensin (OM). Cows were confined and fed diets with 52% of corn silage and 48% of concentrate. No significant interaction between soybean oil and monensin was observed for any measured FA. Monensin increased unsaturated, monounsaturated, and polyunsaturated FA by 9.0, 8.8 and 10.7%, respectively, while supplementation with soybean oil resulted in greater responses: 39.2, 39.3, and 24.2% for the same FA. Soybean oil also reduced short chain FA (43.7%) and medium chain FA (49.1%) and increased long chain FA (55.3%) in this study. The isomers trans-C18:1 were increased by inclusion of oil and monensin in the diet indicating an additive effect for trans-10 C18:1 that was negatively correlated with milk fat content. The CLA isomer cis-9 trans-11 C18:2 was not affected by treatments but soybean oil reduced delta9-desaturase activity. There were interactions between treatment and week of lactation for short and medium chain FA, C14:0, C16:0, cis-9 C18:1 and trans-10. The combination of monensin and soybean oil in diet of lactating dairy cows was responsible for the most significant changes observed in the profile of milk FA

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