The West Midland Familial Hypercholesterolaemia (FH) screening programme: Evaluating the utility of the 12 SNP polygenic risk score (PRS) across ethnic groupings

George, Elizabeth; Bellaby, J.; Day, Shelley; Dhillon, R.; Horton, Sean; Dyer, K. F.; Cramb, R.; Jones, Alice A.; Humphries, SE; Williams, Maggie; Watson, E.; Woodward, Geoff

doi:10.1016/j.athplu.2021.07.012

Cited by 1 publication

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Diagnostic labs in the UK are grouping individuals into low (deciles 1–3), intermediate (deciles 4–5) and high (deciles 6–10) polygenic hypercholesterolaemia score categories in order to simplify the classification of polygenic hypercholesterolaemia ( George et al, 2021 ). This also ensures that the discrepancies in the percent of individuals with LDL-C >4.9 mmol/L in each decile are smoothed for the BC and SA ethnic groups.…”

Section: Discussionmentioning

confidence: 99%

“…Other studies applied the score to define a polygenic cause of high LDL-C in patients with hypercholesterolaemia ( Amor-Salamanca et al, 2017 ; Saadatagah et al, 2021 ). Two of the current NHS Genomic Laboratory Hubs (GLHs) (South West and North East) are including the 12-SNP score within their diagnostic pipelines ( George et al, 2021 ), demonstrating feasibility of implementation. Clinicians receiving these reports are strongly supportive of the roll out to all GLHs and find them helpful for patient management because of the benefit of being able to offer a genetic explanation for mutation negative patients with a biochemical FH phenotype, which may motivate adherence to lifestyle interventions and cholesterol-lowering therapy ( Kullo et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

LDL-C Concentrations and the 12-SNP LDL-C Score for Polygenic Hypercholesterolaemia in Self-Reported South Asian, Black and Caribbean Participants of the UK Biobank

et al. 2022

View full text Add to dashboard Cite

Background: Monogenic familial hypercholesterolaemia (FH) is an autosomal dominant disorder characterised by elevated low-density lipoprotein cholesterol (LDL-C) concentrations due to monogenic mutations in LDLR, APOB, PCSK9, and APOE. Some mutation-negative patients have a polygenic cause for elevated LDL-C due to a burden of common LDL-C-raising alleles, as demonstrated in people of White British (WB) ancestry using a 12-single nucleotide polymorphism (SNP) score. This score has yet to be evaluated in people of South Asian (SA), and Black and Caribbean (BC) ethnicities.Objectives: 1) Compare the LDL-C and 12-SNP score distributions across the three major ethnic groups in the United Kingdom: WB, SA, and BC individuals; 2) compare the association of the 12-SNP score with LDL-C in these groups; 3) evaluate ethnicity-specific and WB 12-SNP score decile cut-off values, applied to SA and BC ethnicities, in predicting LDL-C concentrations and hypercholesterolaemia (LDL-C>4.9 mmol/L).Methods: The United Kingdom Biobank cohort was used to analyse the LDL-C (adjusted for statin use) and 12-SNP score distributions in self-reported WB (n = 353,166), SA (n = 7,016), and BC (n = 7,082) participants. To evaluate WB and ethnicity-specific 12-SNP score deciles, the total dataset was split 50:50 into a training and testing dataset. Regression analyses (logistic and linear) were used to analyse hypercholesterolaemia (LDL-C>4.9 mmol/L) and LDL-C.Findings: The mean (±SD) measured LDL-C differed significantly between the ethnic groups and was highest in WB [3.73 (±0.85) mmol/L], followed by SA [3.57 (±0.86) mmol/L, p < 2.2 × 10−16], and BC [3.42 (±0.90) mmol/L] participants (p < 2.2 × 10−16). There were significant differences in the mean (±SD) 12-SNP score between WB [0.90 (±0.23)] and BC [0.72 (±0.25), p < 2.2 × 10−16], and WB and SA participants [0.86 (±0.19), p < 2.2 × 10−16]. In all three ethnic groups the 12-SNP score was associated with measured LDL-C [R2 (95% CI): WB = 0.067 (0.065–0.069), BC = 0.080 (0.063–0.097), SA = 0.027 (0.016–0.038)]. The odds ratio and the area under the curve for hypercholesterolaemia were not statistically different when applying ethnicity-specific or WB deciles in all ethnic groups.Interpretation: We provide information on the differences in LDL-C and the 12-SNP score distributions in self-reported WB, SA, and BC individuals of the United Kingdom Biobank. We report the association between the 12-SNP score and LDL-C in these ethnic groups. We evaluate the performance of ethnicity-specific and WB 12-SNP score deciles in predicting LDL-C and hypercholesterolaemia.

show abstract

Section: Discussionmentioning

confidence: 99%