Diverse perspectives on interdisciplinarity from the Members of the College of the Royal Society of Canada

Various multiple-disciplinary terms and concepts (although most commonly “interdisciplinarity”, which is used herein) are used to frame education, scholarship, research, and interactions within and outside academia. In principle, the premise of interdisciplinarity may appear to have many strengths; yet, the extent to which interdisciplinarity is embraced by the current generation of academics, the benefits and risks for doing so, and the barriers and facilitators to achieving interdisciplinarity represent inherent challenges. Much has been written on the topic of interdisciplinarity, but to our knowledge there have been few attempts to consider and present diverse perspectives from scholars, artists, and scientists in a cohesive manner. As a team of 57 members from the Canadian College of New Scholars, Artists, and Scientists of the Royal Society of Canada (the College) who self-identify as being engaged or interested in interdisciplinarity, we provide diverse intellectual, cultural, and social perspectives. The goal of this paper is to share our collective wisdom on this topic with the broader community and to stimulate discourse and debate on the merits and challenges associated with interdisciplinarity. Perhaps the clearest message emerging from this exercise is that working across established boundaries of scholarly communities is rewarding, necessary, and is more likely to result in impact. However, there are barriers that limit the ease with which this can occur (e.g., lack of institutional structures and funding to facilitate cross-disciplinary exploration). Occasionally, there can be significant risk associated with doing interdisciplinary work (e.g., lack of adequate measurement or recognition of work by disciplinary peers). Solving many of the world’s complex and pressing problems (e.g., climate change, sustainable agriculture, the burden of chronic disease, and aging populations) demand thinking and working across long-standing, but in some ways restrictive, academic boundaries. Academic institutions and key support structures, especially funding bodies, will play an important role in helping to realize what is readily apparent to all who contributed to this paper—that interdisciplinarity is essential for solving complex problems; it is the new norm. Failure to empower and encourage those doing this research will serve as a great impediment to training, knowledge, and addressing societal issues

Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1

Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value < 1 × 10-5) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p < 1 × 10-5). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10-10, odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

A genome-wide association search for type 2 diabetes genes in African Americans.

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations

Paleopathological Description and Diagnosis of Metastatic Carcinoma in an Early Bronze Age (4588+34 Cal. BP) Forager from the Cis-Baikal Region of Eastern Siberia

<div><p>Extensive osteolytic and osteoblastic lesions were observed on the skeletal remains of an adult male excavated from an Early Bronze Age cemetery dated to 4556+32 years BP, located in the Cis-Baikal region of Siberia (Russian Federation). Lytic lesions ranged in size from several mm to over 60 mm in diameter and had irregular, moth-eaten borders. Many of these lesions destroyed trabecular bone, though a hollowed shell of cortical bone often remained observable. Radiographic analysis revealed numerous lytic lesions within trabecular bone that had not yet affected the cortex. Blastic lesions were identified as spiculated lines, bands, or nodules of mostly immature (woven) bone formed at irregular intervals. Anatomical elements with the greatest involvement included those of the axial skeleton (skull, vertebrae, sacrum, ribs, and sternum) as well as proximal appendicular elements (ossa coxae, proximal femora, clavicles, scapulae, and proximal humeri). Osteocoalescence of destructive foci was observed on the ilium and frontal bone, with the largest lesion found on the right ilium. Differential diagnoses include metastatic carcinoma, mycotic infections, tuberculosis, Langerhan's cell histiocytosis, and multiple myeloma. Based on lesion appearance and distribution, age and sex of the individual, as well as pathogen endemism, the most likely diagnostic option for this set of lesions is metastatic carcinoma. The age and sex of this individual and appearance of the lesions may reflect carcinoma of the lung or, possibly, prostate. This represents one of the earliest cases of metastatic carcinoma worldwide and the oldest case documented thus far from Northeast Asia.</p></div

Osteolytic and mixed (blastic and lytic) lesions on the right lower limb elements; a, complete destruction of posterior third of iliac blade, lateral view; b, acetabulum and pubis, anterior view; c, proximal femur, posteromedial view.

<p>Osteolytic and mixed (blastic and lytic) lesions on the right lower limb elements; a, complete destruction of posterior third of iliac blade, lateral view; b, acetabulum and pubis, anterior view; c, proximal femur, posteromedial view.</p

Large mixed (blastic and lytic) lesion completely destroying the left femoral neck and large portions of the trabecular bone within the trochanters; a, anteromedial view; b, lateral view; c, medial view.

<p>Large mixed (blastic and lytic) lesion completely destroying the left femoral neck and large portions of the trabecular bone within the trochanters; a, anteromedial view; b, lateral view; c, medial view.</p

Burial 3: Diagrammatic representation of skeletal completeness and lesion distribution; a, anterior view; b, posterior view.

<p>Burial 3: Diagrammatic representation of skeletal completeness and lesion distribution; a, anterior view; b, posterior view.</p

Osteolytic and mixed (blastic and lytic) lesions on the left upper limb elements; a, superolateral scapula, anterior view; b, distal shaft of humerus, anterior view.

<p>Osteolytic and mixed (blastic and lytic) lesions on the left upper limb elements; a, superolateral scapula, anterior view; b, distal shaft of humerus, anterior view.</p