Taxonomic identification of whale bones found during archaeological excavations is problematic dueto their typically fragmented state. This difficulty limits understanding of both the past spatio... Show moreTaxonomic identification of whale bones found during archaeological excavations is problematic dueto their typically fragmented state. This difficulty limits understanding of both the past spatio-temporal distributions of whale populations and of possible early whaling activities. To overcomethis challenge, we performed zooarchaeology by mass spectrometry on an unprecedented 719archaeological and palaeontological specimens of probable whale bone from Atlantic Europeancontexts, predominantly dating fromca3500 BCE to the eighteenth century CE. The results showhigh numbers of Balaenidae (many probably North Atlantic right whale (Eubalaena glacialis)) andgrey whale (Eschrichtius robustus) specimens, two taxa no longer present in the eastern NorthAtlantic. This discovery matches expectations regarding the past utilization of North Atlantic rightwhales, but was unanticipated for grey whales, which have hitherto rarely been identified in theEuropean zooarchaeological record. Many of these specimens derive from contexts associated withmediaeval cultures frequently linked to whaling: the Basques, northern Spaniards, Normans,Flemish, Frisians, Anglo-Saxons and Scandinavians. This association raises the likelihood that earlywhaling impacted these taxa, contributing to their extirpation and extinction. Much lower numbersof other large cetacean taxa were identified, suggesting that what are now the most depletedwhales were once those most frequently used. Show less
Potjer, T.P.; Grinten, T.W.J. van der; Lakeman, I.M.M.; Bollen, S.H.; Rodriguez-Girondo, M.; Iles, M.M.; ... ; Stoep, N. van der 2022
Background Familial clustering of melanoma suggests a shared genetic predisposition among family members, but only 10%-40% of familial cases carry a pathogenic variant in a known high-risk melanoma... Show moreBackground Familial clustering of melanoma suggests a shared genetic predisposition among family members, but only 10%-40% of familial cases carry a pathogenic variant in a known high-risk melanoma susceptibility gene. We investigated whether a melanoma-specific Polygenic Risk Score (PRS) is associated with melanoma risk in patients with genetically unexplained familial melanoma. Methods Dutch familial melanoma cases (n=418) were genotyped for 46 SNPs previously identified as independently associated with melanoma risk. The 46-SNP PRS was calculated and standardised to 3423 healthy controls (sPRS) and the association between PRS and melanoma risk was modelled using logistic regression. Within the case series, possible differences were further explored by investigating the PRS in relation to (1) the number of primary melanomas in a patient and (2) the extent of familial clustering of melanoma. Results The PRS was significantly associated with melanoma risk, with a per-SD OR of 2.12 (95% CI 1.90 to 2.35, p<0.001), corresponding to a 5.70-fold increased risk (95% CI 3.93 to 8.28) when comparing the top 90th to the middle 40-60th PRS percentiles. The mean PRS was significantly higher in cases with multiple primary melanomas than in cases with a single melanoma (sPRS 1.17 vs 0.71, p=0.001). Conversely, cases from high-density melanoma families had a lower (but non-significant) mean PRS than cases from low-density families (sPRS 0.60 vs 0.94, p=0.204). Conclusion Our work underlines the significance of a PRS in determining melanoma susceptibility and encourages further exploration of the diagnostic value of a PRS in genetically unexplained melanoma families. Show less
Meta-analysis of 36,760 cases and 375,188 controls identifies 54 loci associated with susceptibility to cutaneous melanoma. Further analysis combining nevus count and hair color GWAS results... Show moreMeta-analysis of 36,760 cases and 375,188 controls identifies 54 loci associated with susceptibility to cutaneous melanoma. Further analysis combining nevus count and hair color GWAS results provide insights into the genetic architecture of melanoma.Most genetic susceptibility to cutaneous melanoma remains to be discovered. Meta-analysis genome-wide association study (GWAS) of 36,760 cases of melanoma (67% newly genotyped) and 375,188 controls identified 54 significant (P < 5 x 10(-8)) loci with 68 independent single nucleotide polymorphisms. Analysis of risk estimates across geographical regions and host factors suggests the acral melanoma subtype is uniquely unrelated to pigmentation. Combining this meta-analysis with GWAS of nevus count and hair color, and transcriptome association approaches, uncovered 31 potential secondary loci for a total of 85 cutaneous melanoma susceptibility loci. These findings provide insights into cutaneous melanoma genetic architecture, reinforcing the importance of nevogenesis, pigmentation and telomere maintenance, together with identifying potential new pathways for cutaneous melanoma pathogenesis. Show less
Epidemiologic studies have reported inconsistent results regarding an association between Parkinson disease (PD) and cutaneous melanoma (melanoma). Identifying shared genetic architecture between... Show moreEpidemiologic studies have reported inconsistent results regarding an association between Parkinson disease (PD) and cutaneous melanoma (melanoma). Identifying shared genetic architecture between these diseases can support epidemiologic findings and identify common risk genes and biological pathways. Here, we apply polygenic, linkage disequilibrium-informed methods to the largest available case-control, genome-wide association study summary statistic data for melanoma and PD. We identify positive and significant genetic correlation (correlation: 0.17, 95% CI 0.10-0.24; P = 4.09 x 10(-06)) between melanoma and PD. We further demonstrate melanoma and PD-inferred gene expression to overlap across tissues (correlation: 0.14, 95% CI 0.06 to 0.22; P = 7.87 x 10(-04)) and highlight seven genes including PIEZO1, TRAPPC2L, and SOX6 as potential mediators of the genetic correlation between melanoma and PD. These findings demonstrate specific, shared genetic architecture between PD and melanoma that manifests at the level of gene expression. Show less
BackgroundPrevious studies of radiological damage in rheumatoid arthritis (RA) have used candidate-gene approaches, or evaluated single genome-wide association studies (GWAS). We undertook the... Show moreBackgroundPrevious studies of radiological damage in rheumatoid arthritis (RA) have used candidate-gene approaches, or evaluated single genome-wide association studies (GWAS). We undertook the first meta-analysis of GWAS of RA radiological damage to: (1) identify novel genetic loci for this trait; and (2) test previously validated variants.MethodsSeven GWAS (2,775 RA cases, of a range of ancestries) were combined in a meta-analysis. Radiological damage was assessed using modified Larsen scores, Sharp van Der Heijde scores, and erosive status. Single nucleotide polymophsim (SNP) associations with radiological damage were tested at a single time-point using regression models. Primary analyses included age and disease duration as covariates. Secondary analyses also included rheumatoid factor (RF). Meta-analyses were undertaken in trans-ethnic and European-only cases.ResultsIn the trans-ethnic primary meta-analysis, one SNP (rs112112734) in close proximity to HLA-DRB1, and strong linkage disequilibrium with the shared-epitope, attained genome-wide significance (P = 4.2x10(-8)). In the secondary analysis (adjusting for RF) the association was less significant (P = 1.7x10(-6)). In both trans-ethnic primary and secondary meta-analyses 14 regions contained SNPs with associations reaching P<5x10(-6); in the European primary and secondary analyses 13 and 10 regions contained SNPs reaching P<5x10(-6), respectively. Of the previously validated SNPs for radiological progression, only rs660895 (tagging HLA-DRB1*04:01) attained significance (P = 1.6x10(-5)) and had a consistent direction of effect across GWAS.ConclusionsOur meta-analysis confirms the known association between the HLA-DRB1 shared epitope and RA radiological damage. The lack of replication of previously validated non-HLA markers highlights a requirement for further research to deliver clinically-useful prognostic genetic markers. Show less
