👤 Markku J Savolainen

Elevated lipoprotein(a) [Lp(a)] is an important genetic risk factor for cardiovascular diseases (CVDs). Because Lp(a)-lowering therapies are limited, prevention focuses on identifying individuals with elevated Lp(a) and optimizing other modifiable risk factors. We aimed to assess the distribution of Lp(a) levels in Finnish adults and examine its association with other CVD risk factors, as well as the awareness, treatment, and control of dyslipidemia. Data were derived from the Healthy Finland health examination survey conducted in 2023, comprising a nationally representative sample of 5,484 adults. Lp(a) levels were categorized using a cut-point at 125 nmol/L. Other CVD risk factors included were dyslipidemia, abnormal glucose metabolism, hypertension, and obesity. Analyses were weighted taking into account the sampling design and non-participation to provide nationally representative results. Mean Lp(a) levels were 41.7 nmol/L (95% CI 39.0-44.3) in men (M) and 41.9 nmol/L (39.7-44.1) in women (W). Elevated Lp(a) was observed in 11.0% of men and 10.4% of women. Dyslipidemia was more prevalent among individuals with elevated Lp(a) (M: 88.1% vs. 78.4% p = 0.003, W: 79.2% vs. 73.2% p = 0.030) but this association reversed after correcting cholesterol for Lp(a). No associations were found between Lp(a) and other cardiometabolic risk factors. Individuals with elevated Lp(a) had slightly lower unawareness (M: 42.3% vs. 47.5%, p = 0.180, W: 38.8% vs.48.4%, p = 0.042) and better treatment (M: 38.1% vs. 31.7%, p = 0.010, W: 29.2% vs. 24.7%, p = 0.090) of dyslipidemia than those with lower levels while no association was found between Lp(a) and dyslipidemia control (M: 81.4% vs. 84.1%, p = 0.520, W: 74.6% vs. 73.0%, p = 0.740). Approximately one in ten Finnish adults had elevated Lp(a), a lower prevalence than in many other European populations but still affecting a substantial share of the population. Elevated Lp(a) was associated with higher prevalence of dyslipidemia prior to Lp(a) correction, but not with other CVD risk factors, and these individuals also showed slightly greater awareness and treatment of dyslipidemia. These findings emphasize the need for comprehensive management of modifiable CVD risk factors to reduce the overall burden of CVDs. Show less

Concentrations of liver enzymes in plasma are widely used as indicators of liver disease. We carried out a genome-wide association study in 61,089 individuals, identifying 42 loci associated with concentrations of liver enzymes in plasma, of which 32 are new associations (P = 10(-8) to P = 10(-190)). We used functional genomic approaches including metabonomic profiling and gene expression analyses to identify probable candidate genes at these regions. We identified 69 candidate genes, including genes involved in biliary transport (ATP8B1 and ABCB11), glucose, carbohydrate and lipid metabolism (FADS1, FADS2, GCKR, JMJD1C, HNF1A, MLXIPL, PNPLA3, PPP1R3B, SLC2A2 and TRIB1), glycoprotein biosynthesis and cell surface glycobiology (ABO, ASGR1, FUT2, GPLD1 and ST3GAL4), inflammation and immunity (CD276, CDH6, GCKR, HNF1A, HPR, ITGA1, RORA and STAT4) and glutathione metabolism (GSTT1, GSTT2 and GGT), as well as several genes of uncertain or unknown function (including ABHD12, EFHD1, EFNA1, EPHA2, MICAL3 and ZNF827). Our results provide new insight into genetic mechanisms and pathways influencing markers of liver function. Show less

Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ∼ 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10⁻⁸), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation. Show less