Quantum biology on the edge of quantum chaos

We give a new explanation for why some biological systems can stay quantum coherent for long times at room temperatures, one of the fundamental puzzles of quantum biology. We show that systems with the right level of complexity between chaos and regularity can increase their coherence time by orders of magnitude. Systems near Critical Quantum Chaos or Metal-Insulator Transition (MIT) can have long coherence times and coherent transport at the same time. The new theory tested in a realistic light harvesting system model can reproduce the scaling of critical fluctuations reported in recent experiments. Scaling of return probability in the FMO light harvesting complex shows the signs of universal return probability decay observed at critical MIT. The results may open up new possibilities to design low loss energy and information transport systems in this Poised Realm hovering reversibly between quantum coherence and classicality

Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney.

Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation

Genetic predictors of lifelong medication-use patterns in cardiometabolic diseases

Peer reviewe

Genetic architecture of human plasma lipidome and its link to cardiovascular disease

AbstractUnderstanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P −8), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rateAbstract Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 ×10−8), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate<0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD

Cardiovascular Risk Factors and MRI Markers of Cerebral Small Vessel Disease

Background and objectives: Cardiovascular risk factors have been implicated in the etiology of cerebral small vessel disease (CSVD); however, whether the associations are causal remains unclear in part due to the susceptibility of observational studies to reverse causation and confounding. Here, we use mendelian randomization (MR) to determine which cardiovascular risk factors are likely to be involved in the etiology of CSVD. Methods: We used data from large-scale genome-wide association studies of European ancestry to identify genetic proxies for blood pressure, blood lipids, body mass index (BMI), type 2 diabetes, smoking initiation, cigarettes per day, and alcohol consumption. MR was performed to assess their association with 3 neuroimaging features that are altered in CSVD (white matter hyperintensities [WMH], fractional anisotropy [FA], and mean diffusivity [MD]) using genetic summary data from the UK Biobank (N = 31,855). Our primary analysis used inverse-weighted median MR, with validation using weighted median, MR-Egger, and a pleiotropy-minimizing approach. Finally, multivariable MR was performed to study the effects of multiple risk factors jointly. Results: MR analysis showed consistent associations across all methods for higher genetically proxied systolic and diastolic blood pressures with WMH, FA, and MD and for higher genetically proxied BMI with WMH. There was weaker evidence for associations between total cholesterol, low-density lipoprotein, smoking initiation, pulse pressure, and type 2 diabetes liability and at least 1 CSVD imaging feature, but these associations were not reproducible across all validation methods used. Multivariable MR analysis for blood pressure traits found that the effect was primarily through genetically proxied diastolic blood pressure across all CSVD traits. Discussion: Genetic predisposition to higher blood pressure, primarily diastolic blood pressure, and to higher BMI is associated with a higher burden of CSVD, suggesting a causal role. Improved management and treatment of these risk factors could reduce the burden of CSVD

Genetic Risk Score for Intracranial Aneurysms:Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity

BACKGROUND: Recently, common genetic risk factors for intracranial aneurysm (IA) and aneurysmal subarachnoid hemorrhage (ASAH) were found to explain a large amount of disease heritability and therefore have potential to be used for genetic risk prediction. We constructed a genetic risk score to (1) predict ASAH incidence and IA presence (combined set of unruptured IA and ASAH) and (2) assess its association with patient characteristics. METHODS: A genetic risk score incorporating genetic association data for IA and 17 traits related to IA (so-called metaGRS) was created using 1161 IA cases and 407 392 controls from the UK Biobank population study. The metaGRS was validated in combination with risk factors blood pressure, sex, and smoking in 828 IA cases and 68 568 controls from the Nordic HUNT population study. Furthermore, we assessed association between the metaGRS and patient characteristics in a cohort of 5560 IA patients. RESULTS: Per SD increase of metaGRS, the hazard ratio for ASAH incidence was 1.34 (95% CI, 1.20-1.51) and the odds ratio for IA presence 1.09 (95% CI, 1.01-1.18). Upon including the metaGRS on top of clinical risk factors, the concordance index to predict ASAH hazard increased from 0.63 (95% CI, 0.59-0.67) to 0.65 (95% CI, 0.62-0.69), while prediction of IA presence did not improve. The metaGRS was statistically significantly associated with age at ASAH (β=-4.82×10(-3) per year [95% CI, -6.49×10(-3) to -3.14×10(-3)]; P=1.82×10(-8)), and location of IA at the internal carotid artery (odds ratio=0.92 [95% CI, 0.86-0.98]; P=0.0041). CONCLUSIONS: The metaGRS was predictive of ASAH incidence, although with limited added value over clinical risk factors. The metaGRS was not predictive of IA presence. Therefore, we do not recommend using this metaGRS in daily clinical care. Genetic risk does partly explain the clinical heterogeneity of IA warranting prioritization of clinical heterogeneity in future genetic prediction studies of IA and ASAH

Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices

AbstractAutosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholesterol, and triglycerides (min P = 8.5 × 10−72), with similar effects for males and females. Chromosome Xq23 lipid-lowering alleles are associated with reduced odds for CHD among 42,545 cases and 591,247 controls (P = 1.7 × 10−4), and reduced odds for diabetes mellitus type 2 among 54,095 cases and 573,885 controls (P = 1.4 × 10−5). Although we observe an association with increased BMI, waist-to-hip ratio adjusted for BMI is reduced, bioimpedance analyses indicate increased gluteofemoral fat, and abdominal MRI analyses indicate reduced visceral adiposity. Co-localization analyses strongly correlate increased CHRDL1 gene expression, particularly in adipose tissue, with reduced concentrations of blood lipids.Abstract Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholesterol, and triglycerides (min P = 8.5 × 10−72), with similar effects for males and females. Chromosome Xq23 lipid-lowering alleles are associated with reduced odds for CHD among 42,545 cases and 591,247 controls (P = 1.7 × 10−4), and reduced odds for diabetes mellitus type 2 among 54,095 cases and 573,885 controls (P = 1.4 × 10−5). Although we observe an association with increased BMI, waist-to-hip ratio adjusted for BMI is reduced, bioimpedance analyses indicate increased gluteofemoral fat, and abdominal MRI analyses indicate reduced visceral adiposity. Co-localization analyses strongly correlate increased CHRDL1 gene expression, particularly in adipose tissue, with reduced concentrations of blood lipids

Women in technology-oriented fields

This study focuses on investigating the main elements that have an effect on women’s decisions to enter a career in technology-oriented fields, and more specifically, to discover whether studying crafts, especially technical work, during basic education affects their decisions in this context. The study was carried out using a semi-structured questionnaire, and the data consist of the responses from 12 female technology education teachers and 12 female engineering students. A qualitative theory oriented content analysis was carried out through identifying, coding, analysing and reporting the patterns within the data. The findings revealed that the most influential career anchor identified by all these women was a technical or functional competence. Secondly, their familiarity with the field was a relatively important element. These findings suggest some positive perspectives on women’s interests in technology-oriented career paths, and indicating that supportive interventions can be implemented.peerReviewe

Women in technology-oriented fields

This study focuses on investigating the main elements that have an effect on women's decisions to enter a career in technology-oriented fields, and more specifically, to discover whether studying crafts, especially technical work, during basic education affects their decisions in this context. The study was carried out using a semi-structured questionnaire, and the data consist of the responses from 12 female technology education teachers and 12 female engineeringstudents. A qualitative theory oriented content analysis was carried out through identifying, coding, analysing and reporting the patterns within the data.The findings revealed that the most influential career anchor identified by all these women was a technical or functional competence. Secondly, their familiarity with the field was a relatively important element. These findings suggest some positive perspectives on women's interests in technology-oriented career paths, and indicating that supportive interventions can be implemented