The role of liver fat in cardiometabolic diseases is highlighted by genome-wide association study of MRI-derived measures of body composition
van der Meer, D.; Gurholt, T. P.; Sonderby, I. E.; Shadrin, A.; Hindley, G. F.; Rahman, Z.; Glaso de Lange, A.-M.; Frei, O.; Leinhard, O. D.; Linge, J.; Simon, R.; Westlye, L. T.; Halvorsen, S.; Dale, A.; Karlsen, T. H.; Kaufmann, T.; Andreassen, O. A.
Show abstract
Background & AimsObesity and associated morbidities, metabolic associated liver disease (MAFLD) included, constitute some of the largest public health threats worldwide. Body composition and related risk factors are known to be heritable and identification of their genetic determinants may aid in the development of better prevention and treatment strategies. Recently, large-scale whole-body MRI data has become available, providing more specific measures of body composition than anthropometrics such as body mass index. Here, we aimed to elucidate the genetic architecture of body composition, by conducting the first genome-wide association study (GWAS) of these MRI-derived measures. MethodsWe ran both univariate and multivariate GWAS on fourteen MRI-derived measurements of adipose and muscle tissue distribution, derived from scans from 34,036 White European UK Biobank participants (mean age of 64.5 years, 51.5% female). ResultsThrough multivariate analysis, we discovered 108 loci with distributed effects across the body composition measures and 256 significant genes primarily involved in immune system functioning. Liver fat stood out, with a highly discoverable and oligogenic architecture and the strongest genetic associations. Comparison with 21 common cardiometabolic traits revealed both shared and specific genetic influences, with higher mean heritability for the MRI measures (h2=.25 vs. .16, p=1.4x10-6). We found substantial genetic correlations between the body composition measures and a range of cardiometabolic diseases, with the strongest correlation between liver fat and type 2 diabetes (rg=.48, p=1.6x10-22). ConclusionsThese findings show that MRI-derived body composition measures complement conventional body anthropometrics and other biomarkers of cardiometabolic health, highlighting the central role of liver fat, and improving our knowledge of the genetic architecture of body composition and related diseases.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Association of machine learning-derived measures of body fat distribution with cardiometabolic diseases in >40,000 individuals 97%
- Twin pair analysis uncovers novel links between DNA methylation, mitochondrial DNA quantity and obesity 95%
- Comprehensive genomic analysis of dietary habits in UK Biobank identifies hundreds of genetic loci and establishes causal relationships between educational attainment and healthy eating 94%
Similar papers in this journal
- The extracellular vesicle transcriptome provides tissue-specific functional genomic annotation relevant to disease susceptibility in obesity 94%
- Genome-wide study on 72,298 Korean individuals in Korean biobank data for 76 traits identifies hundreds of novel loci 92%
- Polygenic scores capture genetic modification of the adiposity-cardiometabolic risk factor relationship 92%
Similar papers in this journal
- Characterizing common and rare variations in non-traditional glycemic biomarkers using multivariate approaches on multi-ancestry ARIC study 94%
- Plasma proteomic signatures of adiposity are associated with cardiovascular risk factors and type 2 diabetes risk in a multi-ethnic Asian population 94%
- Integrative proteogenomic analyses provide novel interpretations of type 1 diabetes risk loci through circulating proteins 92%
Similar papers in this journal
- Composite trait Mendelian Randomization reveals distinct metabolic and lifestyle consequences of differences in body shape 95%
- Amerind ancestry predicts the impact of FADS genetic variation on omega-3 PUFA deficiency, cardiometabolic and inflammatory risk in Hispanic populations 93%
- Molecular programming in utero modulates hepatic lipid metabolism and adult metabolic risk in obese mother offspring in a sex-specific manner 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.