1.
van der Meer, Dennis, et al.
(författare)
The role of liver fat in cardiometabolic diseases is highlighted by genome-wide association study of MRI-derived measures of body composition
2022
Annan publikation (övrigt vetenskapligt/konstnärligt) 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=1.4×10−6). 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=1.6×10−22).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.
3.
Helms, Gunther, et al.
(författare)
Correction of FLASH-based MT saturation in human brain for residual bias of B1-inhomogeneity at 3T
2021
Annan publikation (övrigt vetenskapligt/konstnärligt) abstract
Background: Magnetization transfer (MT) saturation reflects the additional saturation of the MRI signal imposed by an MT pulse and is largely driven by the saturation of the bound pool. This reduction of the bound polarization by the MT pulse is less efficient than predicted by the differential B1-square law of absorption. Thus, B1 inhomogeneities lead to a residual bias in the MT saturation maps. We derive a heuristic correction to reduce this bias for a widely used multi-parameter mapping protocol at 3T. Methods: The amplitude of the MT pulse was varied via the nominal flip angle to mimic variations in B1. The MT saturation's dependence on the actual flip angle features a linear correction term, which was determined separately for gray and white matter. Results: The deviation of MT saturation from differential B1-square law is well described by a linear decrease with the actual flip angle of the MT pulse. This decrease showed no significant differences between gray and white matter. Thus, the post hoc correction does not need to take different tissue types into account. Bias-corrected MT saturation maps appeared more symmetric and highlighted highly myelinated tracts. Discussion:Our correction involves a calibration that is specific for the MT pulse. While it can also be used to rescale nominal flip angles, different MT pulses and/or protocols will require individual calibration. Conclusion: The suggested B1 correction of the MT maps can be applied post hoc using an independently acquired flip angle map.
