Fig. 1: Spectrum of pathogenic variation in clinically relevant genes among Singaporeans.
From: Analysis of clinically relevant variants from ancestrally diverse Asian genomes
a Carrier frequencies of ACMG SF v3.0 genes associated with dominant disorders compared across the three main ancestry groups. The disorders are further sub-classified into three main disease domains for comparison (cancer, cardiovascular, lipid disorders). Carrier frequency of P/LP variants in lipid disorder genes were significantly higher among Chinese compared to Indians (p = 7.93 × 10−5) and Malays (p = 1.70 × 10−3). Statistical significance was evaluated by two-sided Fisher’s exact test, with Benjamini-Hochberg correction for multiple testing. Adjusted p < 0.05 was considered significant, ns: not significant. CH: Chinese, IND: Indian, MY: Malay. b Differential distribution of carrier frequencies across ancestries for dominantly inherited genetic disorders associated with ACMG SF v3.0 medically actionable genes, or non-ACMG SF v3.0 genes with a carrier frequency >0.5%. c Genes of recessive conditions with significant differences in carrier frequency of P/LP variants across ancestry groups. Colour scale maps to row-wise z-scores, obtained by subtracting from each gene-level carrier frequency the row average and then dividing the value by the row standard deviation. Genes in red fonts are recommended by ACMG for carrier screening. Genes in bold fonts are part of the ACMG SF v3.0 list. The disorder domain associated with pathogenic alteration of the indicated gene is represented in the dot matrix. CVD cardiovascular disorders, Derm dermatological disorders, Metab. metabolic (including lysosomal storage, mitochondrial, metabolic disorders), Gastro-HPB gastro-hepato-pancreato biliary disorders, Haem/Immuno haematological/immunological disorders, MCA multiple congenital anomalies, Neuro neurological (including neurologic, neuromuscular, neurodegenerative disorders), Others: including cancer, respiratory, genitourinary disorders.
