Fig. 2: Evaluating the influence of genetic admixture and potentially pathogenic VUS in SG10K_Health cohort.

a ADMIXTURE analysis of inferred genetic ancestral components at K = 3 juxtaposed with self-reported ancestry for the 9,051 Singaporean individuals. NA: not available. b The proportion of genetic ancestral components tracked consistently with carrier status of pathogenic/likely pathogenic (P/LP) variants specific to the associated ancestry group across Singaporean Chinese (CH), Indian (IND) and Malay (MY) individuals (Chinese-specific variant carriers/non-carriers: (CH) 455/5047, (IND) 2/1939, (MY) 26/1582; Indian-specific variant carriers/non-carriers: (CH) 3/5499, (IND) 147/1794, (MY) 19/1589; Malay-specific variant carriers/non-carriers: (CH) 2/5500, (IND) 2/1939, (MY) 24/1584). Pairwise differences between carriers and non-carriers were evaluated by two-sided Wilcoxon rank-sum test. p < 0.05 was considered significant. ns: not significant. c Juxtaposition of P/LP variants with potentially pathogenic variants of uncertain significance (missense and cryptic splice variants) classified as VUS-FP, identified in genes from the ACMG SF v3.0 list. Mode of inheritance and disease domain associated for each gene are indicated in the dot matrix below. PTV: protein-truncating variant. d Carriers of VUS-FP variants (n = 5) identified in LDLR demonstrated LDL cholesterol range that is consistent with carriers of P/LP variants (n = 25) and is higher compared to non-carriers (n = 4397). An LDL cholesterol level of ≥4.1 mmol/L is classified as high by the Ministry of Health Singapore. p values were derived from binomial logistic regression comparing LDL cholesterol levels against LDLR variant status, correcting for age, sex, genetic ancestry, and lipid-lowering medication intake. All box plots extend from the 25th to 75th percentiles and the length of the whiskers are defined as follows: upper whisker =  min(maximum_value, Q3 + 1.5*IQR), lower whisker = max(mininum_value, Q1–1.5*IQR), where IQR is interquartile range, Q3 is third quartile, Q1 is first quartile. Horizontal line in the box represents the median.