Genetic architecture of human plasma lipidome and its link to cardiovascular disease

AbstractUnderstanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P −8), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rateAbstract Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 ×10−8), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate<0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD

The hidden epidemic : Uncovering incidental fatty liver disease and its metabolic comorbidities by datamining in a hospital data lake – A real-world cohort study

Aims: To identify individuals with incidental fatty liver disease (FLD), and to evaluate its prevalence, metabolic co-morbidities and impact on follow-up. Methods: We leveraged the data-lake of Helsinki Uusimaa Hospital district (Finland) with a population of 1.7 million (specialist and primary care). A phrase recognition script on abdominal imaging reports (2008–2020) identified/excluded FLD or cirrhosis; we extracted ICD-codes, laboratory and BMI data. Results: Excluding those with other liver diseases, the prevalence of FLD was 29% (steatosis yes/no, N=61,271/155,521; cirrhosis, N=3502). The false positive and negative rates were 5–6%. Only 1.6% of the FLD cases had the ICD code recorded and 32% had undergone full clinical evaluation for associated co-morbidities. Of the 35–65-year-old individuals with FLD, 20% had diabetes, 42% prediabetes and 28% a high liver fibrosis index. FLD was independently predicted by diabetes (OR 1.56, CI 1.46–1.66, p = 2.3 * 10^-41), BMI (1.46, 1.42–1.50, p = 1.7 * 10^-154) and plasma triglyceride level (1.5, 1.43–1.57, p = 3.5 * 10^-68). Alanine aminotransferase level mildly increased (1.12, 1.08–1.16, p = 2.2 * 10^-9) and high age decreased the risk (0.92, 0.89–0.94, p = 4.65*10^-09). Half of the cases had normal ALT. Conclusions: The incidental radiological finding of FLD is reliable and associated with metabolic risks but largely ignored, although it should lead to metabolic and hepatic follow-up.Peer reviewe