Atrial Fibrillation and Cognitive Decline–The Role of Subclinical Cerebral Infarcts: The Atherosclerosis Risk in Communities Study

The mechanism underlying the association of atrial fibrillation (AF) with cognitive decline in stroke-free individuals is unclear. We examined the association of incident AF with cognitive decline in stroke-free individuals, stratified by subclinical cerebral infarcts (SCIs) on brain MRI scans

Fine-mapping of lipid regions in global populations discovers ethnic-specific signals and refines previously identified lipid loci

Genome-wide association studies have identified over 150 loci associated with lipid traits, however, no large-scale studies exist for Hispanics and other minority populations. Additionally, the genetic architecture of lipid-influencing loci remains largely unknown. We performed one of the most racially/ethnically diverse fine-mapping genetic studies of HDL-C, LDL-C, and triglycerides to-date using SNPs on the MetaboChip array on 54,119 individuals: 21,304 African Americans, 19,829 Hispanic Americans, 12,456 Asians, and 530 American Indians. The majority of signals found in these groups generalize to European Americans. While we uncovered signals unique to racial/ethnic populations, we also observed systematically consistent lipid associations across these groups. In African Americans, we identified three novel signals associated with HDL-C (LPL, APOA5, LCAT) and two associated with LDL-C (ABCG8, DHODH). In addition, using this population, we refined the location for 16 out of the 58 known MetaboChip lipid loci. These results can guide tailored screening efforts, reveal population-specific responses to lipid-lowering medications, and aid in the development of new targeted drug therapies

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

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

Shared Genetic Risk Factors of Intracranial, Abdominal, and Thoracic Aneurysms

Background: Intracranial aneurysms (IAs), abdominal aortic aneurysms (AAAs), and thoracic aortic aneurysms (TAAs) all have a familial predisposition. Given that aneurysm types are known to co‐occur, we hypothesized that there may be shared genetic risk factors for IAs, AAAs, and TAAs. Methods and Results: We performed a mega‐analysis of 1000 Genomes Project‐imputed genome‐wide association study (GWAS) data of 4 previously published aneurysm cohorts: 2 IA cohorts (in total 1516 cases, 4305 controls), 1 AAA cohort (818 cases, 3004 controls), and 1 TAA cohort (760 cases, 2212 controls), and observed associations of 4 known IA, AAA, and/or TAA risk loci (9p21, 18q11, 15q21, and 2q33) with consistent effect directions in all 4 cohorts. We calculated polygenic scores based on IA‐, AAA‐, and TAA‐associated SNPs and tested these scores for association to case‐control status in the other aneurysm cohorts; this revealed no shared polygenic effects. Similarly, linkage disequilibrium–score regression analyses did not show significant correlations between any pair of aneurysm subtypes. Last, we evaluated the evidence for 14 previously published aneurysm risk single‐nucleotide polymorphisms through collaboration in extended aneurysm cohorts, with a total of 6548 cases and 16 843 controls (IA) and 4391 cases and 37 904 controls (AAA), and found nominally significant associations for IA risk locus 18q11 near RBBP8 to AAA (odds ratio [OR]=1.11; P=4.1×10−5) and for TAA risk locus 15q21 near FBN1 to AAA (OR=1.07; P=1.1×10−3). Conclusions: Although there was no evidence for polygenic overlap between IAs, AAAs, and TAAs, we found nominally significant effects of two established risk loci for IAs and TAAs in AAAs. These two loci will require further replication

The Wanderings of Io: Spatial Readings into Greek Mythology

International audienceThe paper presents a spatial analysis of the myth of Io, the unfortunate maiden, who was turned by Zeus into a heifer and thus traveled the world. The analysis will conclude in a reconstruction of a paradigmatic spatial perception, named the maritime mediation model, which was held by Greek society in the archaic and early classical periods. The model was based on the Mediterranean Sea and the multidirectional maritime networks it offered.Le document présente une analyse spatiale du mythe d’Io, la malheureuse jeune fille qui a été transformée par Zeus en génisse et ainsi a parcouru le monde. L’analyse résultera en la reconstruction d’une perception spatiale paradigmatique, nommée le modèle de médiation maritime, qui était celui de la société grecque dans la période archaïque et au début de la période classique. Le modèle est centré sur la mer Méditerranée et ses réseaux maritimes multidirectionnels

The Wanderings of Io: Spatial Readings into Greek Mythology

Le document présente une analyse spatiale du mythe d’Io, la malheureuse jeune fille qui a été transformée par Zeus en génisse et ainsi a parcouru le monde. L’analyse résultera en la reconstruction d’une perception spatiale paradigmatique, nommée le modèle de médiation maritime, qui était celui de la société grecque dans la période archaïque et au début de la période classique. Le modèle est centré sur la mer Méditerranée et ses réseaux maritimes multidirectionnels.The paper presents a spatial analysis of the myth of Io, the unfortunate maiden, who was turned by Zeus into a heifer and thus traveled the world. The analysis will conclude in a reconstruction of a paradigmatic spatial perception, named the maritime mediation model, which was held by Greek society in the archaic and early classical periods. The model was based on the Mediterranean Sea and the multidirectional maritime networks it offered

Coming out : sexual orientation disclosure to siblings

This qualitative study explores LGBTQ individuals\u27 experiences navigating sexual orientation disclosure to their sibling(s). The purpose of the study was to examine the role siblings play in sexual orientation disclosure, how and why LGBTQ identified individuals \u27come out\u27 to their sibling(s), and provide a glimpse into their experiences of this disclosure. Eleven individuals, ages 25–32 who identified as Lesbian, Gay, Bi–sexual, Transgender or Queer were interviewed via open–ended, semi–structured interviews. LGBTQ participants were asked to speak about their sibling(s) relationship prior to and following their sexual orientation disclosure and the trajectory of their sexual orientation awareness through the process of \u27coming out\u27. Though each story was unique and individual, common themes emerged across interviews including periods of silence and secrecy, sense of relief, honesty and the intersection of self– discovery and the effects of exposure on the sibling(s) relationship. Findings from this study showed that the nature of the sibling relationship, moments of opportunity and circumstances were primary determinants of disclosure to siblings. Individuals shared diverse stories about their experiences \u27coming out\u27 that ranged in length, intensity and effect; all of which are difficult to isolate from external influences. Siblings and the sibling relationship played a role in LGBTQ individuals\u27 sexual orientation disclosure whether it functioned as a bridge between familial generations and society or a questioning voice. Sexual orientation disclosure is multifaceted and \u27coming out\u27 to siblings is just one aspect of this ongoing intimate process that contributes to a deeper understanding of the LGBTQ community