Biology subjects

Palmer, C. N.

Publications and source records attributed to Palmer, C. N..

3 recordsLinked to original sources

bioRxiv2026

PPARδ Expression and Prognosis in Resected Pancreatic Cancer: A Retrospective Single-Centre Study

Background: Pancreatic cancer remains one of the most lethal malignancies, with limited curative options and poor long-term outcomes. Nuclear receptors, including PPAR{delta}, have been implicated in tumour progression. Methods: Retrospectively, we analysed 25 resected pancreatic cancer specimens from patients undergoing Whipple!s procedure (pancreatoduodenectomy) between 2000 and 2009. Immunohistochemistry was performed for PPAR{delta}. Tumour and stromal staining were assessed and correlated with clinicopathological features and survival data. Results: PPAR{delta} expression was observed in the majority of samples. This preliminary analysis suggests that PPAR{delta} expression is associated with adverse clinicopathological features and poorer survival. Conclusions: PPAR{delta} immunohistochemistry may identify a subset of pancreatic cancers with more aggressive biology. Larger studies are warranted to validate these findings.

cancer biology↗

bioRxiv2022

Common and distinct genetic architecture of age at diagnosis of diabetes in South Indian and European populations

South Asians are diagnosed with type 2 diabetes (T2D) more than a decade earlier in life than seen in European populations. We hypothesised that studying the genomics of age of onset in these populations may give insight into earlier age at onset of T2D among individuals of South Asian descent. We conducted a meta-analysis of GWAS of age at diagnosis of T2D in 34,001 individuals from four independent cohorts of European and Asian Indians. We identified two signals near the TCF7L2 and CDKAL1 associated with age at onset of T2D. The strongest genome-wide significant variants at chromosome 10q25.3 in TCF7L2 (lead SNP rs7903146; p = 2.4 x10-12; p-het =0.01; Beta = -0.436; SE = 0.02) and chromosome 6 p22.3 in CDKAL1 (rs9368219; p = 2.29 x10-8; p-het =0.007; Beta = -0.053; SE=0.01) were directionally consistent across ethnic groups and present at similar frequencies, however both loci harboured additional independent signals that were only present in the South Asian cohorts. A genome wide signal was also obtained at chromosome 10q26.12 in WDR11 (rs3011366; p = 2.4 x10-8; p-het =0.25; Beta = 1.44; SE=0.25) specifically in the South Asian Indian cohorts. Our study estimated 17% of heritability (h2) for age onset of T2D among South Indians; higher than the 5% heritability we observed in Europeans suggesting different genetic architectures between these populations. We further estimated the Asian Indian genome-wide polygenic risk score for T2D risk and identified that the variance explained by the Indian specific polygenic risk score (PRS) for age at onset of T2D is substantially higher (2%) in an independent cohort of Asian Indians compared to that seen in White Europeans (<0.1%). This reveals that although variants do exist that are shared between the two population there are also genetic disparities of age onset of T2D between the ethnicities. Author SummaryRecent large multi-ancestry genome-wide meta-analyses have identified over 277 genetic loci associated with type 2 diabetes (T2D). Most association studies for T2D have focused on populations of European ancestry, and the specific genetic architecture of T2D in the South Asian population has not been extensively investigated. Increasing evidence indicates that the prevalence of T2D is higher in South Asians with a strikingly earlier age at diagnosis when compared to Europeans. Genome-wide association studies (GWAS) on age at age at diagnosis of T2D are limited and can help elucidate underlying mechanisms. We conducted the largest meta-analysis to date of genome-wide association studies of age at diagnosis as a surrogate for age of onset of T2D in South Indians and Europeans. Our trans-ancestry meta-analysis identified genetic loci near TCF7L2 and CDKAL1 with substantial ethnic heterogeneity in both allele frequencies and effect sizes in early diagnosis with T2D. Two novel variants near TCF7L2 (rs570193324) and CDKAL1 (rs143316471) were associated with age of diagnosis of T2D only in South Indians and were present at much lower frequency in the European populations. Heritability estimates for age of onset were much stronger in Asian Indians compared to Europeans and a polygenic risk score was constructed using a South Indians, which explained about 2% trait variance compared to European ancestry (<0.1%). Our novel findings provide a better understanding of ethnic differences in the age at onset of T2D and indicate the potential importance of ethnic differences in the genetic architecture underpinning T2D.

genetics↗

bioRxiv2020

A genome-wide association study finds genetic variants associated with neck or shoulder pain in UK Biobank

BackgroundCommon types of musculoskeletal conditions include pain in the neck and shoulder areas. This study seeks to identify the genetic variants associated with neck or shoulder pain based on a genome-wide association approach using 203,309 subjects from the UK Biobank cohort and look for replication evidence from the Generation Scotland: Scottish Family Health Study (GS:SFHS) and TwinsUK. MethodsCases in the UK Biobank were determined by a question which asked the participants if they had experienced pain in the neck or shoulder in the previous month influencing daily activities. Controls were the UK Biobank participants who reported no pain anywhere in the last month. A genome-wide association study was performed adjusting for age, sex, BMI and 9 population principal components. Significant and independent genetic variants were then sent to GS:SFHS and TwinsUK for replication. ResultsWe identified 3 genetic loci that were associated with neck or shoulder pain in the UK Biobank samples. The most significant locus was in an intergenic region in chromosome 17, rs12453010, having P = 1.66 x 10-11. The second most significant locus was located in the FOXP2 gene in chromosome 7 with P = 2.38 x 10-10 for rs34291892. The third locus was located in the LINC01572 gene in chromosome 16 with P = 4.50 x 10-8 for rs62053992. In the replication stage, among 4 significant and independent genetic variants, rs2049604 in the FOXP2 gene and rs62053992 in the LINC01572 gene were weakly replicated in GS:SFHS (P = 0.0240 and P = 0.0202, respectively). None of the single nucleotide polymorphisms (SNPs) were replicated in the TwinsUK cohort (P > 0.05). ConclusionsWe have identified 3 loci associated with neck or shoulder pain in the UK Biobank cohort, two of which were weakly supported in a replication cohort. Further evidence is needed to confirm their roles in neck or shoulder pain. SignificanceThis is the first genome-wide association study on neck or shoulder pain. We have identified 3 genetic loci (an intergenic region in chromosome 17, the FOXP2 gene in chromosome 7, and the LINC01572 gene in chromosome 16) that are associated with neck or shoulder pain using the UK Biobank cohort, among which the FOXP2 gene and the LINC01572 gene were weakly replicated by the Generation Scotland: Scottish Family Health Study (P < 0.05). The SNP heritability was 0.11, indicating neck or shoulder pain is a heritable trait. The tissue expression analysis suggested that neck or shoulder pain was related to multiple brain tissues, indicating the involvement of neuron function. The results will inform further research in the characterisation of the mechanisms of neck or shoulder pain.

genetics↗