Genetic architecture of 11 abdominal organ traits derived from abdominal MRI using deep learning

Liu, Yi; Basty, Nicolas; Whitcher, Brandon; Bell, Jimmy D.; Sorokin, Elena P.; Bruggen, Nick van; Thomas, E. Louise; Cule, Madeleine

doi:10.1101/2020.07.14.187070

Cited by 27 publications

(55 citation statements)

References 115 publications

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“…However, 10 other significant variants were identified as genome-wide significant (P<5x10 -8 ) in UK Biobank. Of these 10 significant variants [29], one variant showed a suggestive association with percent pancreatic fat in our MEC-APS study population (rs118005033: Beta = 0.10, P = 0.01), three . CC-BY 4.0 International license available under a (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.…”

Section: Discussionmentioning

confidence: 86%

“…In a preprint manuscript on bioRxiv, Liu and colleagues (2020) conducted GWASes of 11 MRIassessed abdominal organ and adiposity measurements , including pancreatic volume and percent fat based on 30,000 UK Biobank participants of White British ancestry [29]. Regarding the two genome-wide significant variants in our study, rs73449607 was not observed in the European American population in MEC-APS and rs79967607 was not found to be genome-wide significantly associated with pancreatic fat in the UK Biobank population.…”

Section: Discussionmentioning

confidence: 99%

“…However, 10 other significant variants were identified as genome-wide significant (P<5×10 -8 ) in UK Biobank. Of these 10 significant variants [29], one variant showed a suggestive association with percent pancreatic fat in our MEC-APS study population (rs118005033: Beta = 0.10, P = 0.01), three variants were not associated with percent pancreatic fat (rs4733612: Beta = −0.07, P = 0.16; rs2270911: Beta = 0.04, P = 0.25; and rs13040225, Beta = 0.04, P = 0.27), and the remaining six variants were not in our final data set.…”

Section: Discussionmentioning

confidence: 99%

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Genome-wide Association Study of Pancreatic Fat: The Multiethnic Cohort Adiposity Phenotype Study

Streicher

Lim

Park

et al. 2021

Preprint

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Several studies have found associations between higher pancreatic fat content and adverse health outcomes, such as diabetes and the metabolic syndrome, but investigations into the genetic contributions to pancreatic fat are limited. This genome-wide association study, comprised of 804 participants with MRI-assessed pancreatic fat measurements, was conducted in the ethnically diverse Multiethnic Cohort-Adiposity Phenotype Study (MEC-APS). Two genetic variants reaching genome-wide significance, rs73449607 on chromosome 13q21.2 (Beta = −0.67, P = 4.50×10-8) and rs7996760 on chromosome 6q14 (Beta = −0.90, P = 4.91×10-8) were associated with percent pancreatic fat on the log scale. Rs73449607 was most common in the African American population (13%) and rs79967607 was most common in the European American population (6%). Rs73449607 was also suggestively associated with lower risk of type 2 diabetes (OR = 0.95, 95% CI = 0.89-1.00, P = 0.047) in the Population Architecture Genomics and Epidemiology (PAGE) Study and the DIAbetes Genetics Replication and Meta-analysis (DIAGRAM), which included substantial numbers of non-European ancestry participants (53,102 cases and 193,679 controls). Rs73449607 is located in an intergenic region between GSX1 and PLUT, and rs79967607 is in intron 1 of EPM2A. PLUT, a linkRNA, regulates transcription of an adjacent gene, PDX1, that controls beta-cell function in the mature pancreas, and EPM2A encodes the protein laforin, which plays a critical role in regulating glycogen production. If validated, these variants may suggest a genetic component for pancreatic fat and a common etiologic link between pancreatic fat and type 2 diabetes.

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Genome-wide Association Study of Pancreatic Fat: The Multiethnic Cohort Adiposity Phenotype Study

Streicher

Lim

Park

et al. 2021

Preprint

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“…Raw MR images were obtained from the UKBB Abdominal Protocol 35 and preprocessed as previously reported 36,37 . The data were acquired on the same model, a Siemens Aera 1.5 T scanner (Syngo MR D13) (Siemens, Erlangen, Germany), across three sites (Stockport, Newcastle, Reading, UK).…”

Section: Datamentioning

confidence: 99%

Large-scale analysis of iliopsoas muscle volumes in the UK Biobank

Fitzpatrick

Basty

Cule

et al. 2020

Sci Rep

Self Cite

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Psoas muscle measurements are frequently used as markers of sarcopenia and predictors of health. Manually measured cross-sectional areas are most commonly used, but there is a lack of consistency regarding the position of the measurement and manual annotations are not practical for large population studies. We have developed a fully automated method to measure iliopsoas muscle volume (comprised of the psoas and iliacus muscles) using a convolutional neural network. Magnetic resonance images were obtained from the UK Biobank for 5000 participants, balanced for age, gender and BMI. Ninety manual annotations were available for model training and validation. The model showed excellent performance against out-of-sample data (average dice score coefficient of 0.9046 ± 0.0058 for six-fold cross-validation). Iliopsoas muscle volumes were successfully measured in all 5000 participants. Iliopsoas volume was greater in male compared with female subjects. There was a small but significant asymmetry between left and right iliopsoas muscle volumes. We also found that iliopsoas volume was significantly related to height, BMI and age, and that there was an acceleration in muscle volume decrease in men with age. Our method provides a robust technique for measuring iliopsoas muscle volume that can be applied to large cohorts.

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“…(7,8) Interestingly, the preprint of a recent study identifies rs4240624 as the strongest genome-wide genetic determinant of liver volume whereas no association with liver fat or liver iron content was observed. (9) Overall, the mechanisms for how the PPP1R3B polymorphism contributes to liver CT attenuation or liver metabolism are unclear.…”

mentioning

confidence: 99%

Protein Phosphatase 1 Regulatory Subunit 3B Genotype at rs4240624 Has a Major Effect on Gallbladder Bile Composition

et al. 2020

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The protein phosphatase 1 regulatory subunit 3B (PPP1R3B) gene is a target of farnesoid X receptor (FXR), which is a major regulator of bile acid metabolism. Both PPP1R3B and FXR have been suggested to take part in glycogen metabolism, which may explain the association of PPP1R3B gene variants with altered hepatic computed tomography attenuation. We analyzed the effect of PPP1R3B rs4240624 variant on bile acid composition in individuals with obesity. The study cohort consisted of 242 individuals from the Kuopio Obesity Surgery Study (73 men, 169 women, age 47.6 ± 9.0 years, body mass index 43.2 ± 5.4 kg/m 2) with PPP1R3B genotype and liver RNA sequencing (RNA-seq) data available. Fasting plasma and gallbladder bile samples were collected from 50 individuals. Bile acids in plasma did not differ based on the PPP1R3B rs4240624 genotype. However, the concentration of total bile acids (109 ± 55 vs. 35 ± 19 mM; P = 1.0 × 10 −5) and all individual bile acids (also 7α-hydroxy-4-cholesten-3-one [C4]) measured from bile were significantly lower in those with the AG genotype compared to those with the AA genotype. In addition, total cholesterol (P = 0.011) and phospholipid (P = 0.001) levels were lower in individuals with the AG genotype, but cholesterol saturation index did not differ, indicating that the decrease in cholesterol and phospholipid levels was secondary to the change in bile acids. Liver RNA-seq data demonstrated that expression of PPP1R3B, tankyrase (TNKS), Homo sapiens chromosome 8 clone RP11-10A14.5 (AC022784.1 [LOC157273]), Homo sapiens chromosome 8 clone RP11-375N15.1 (AC021242.1), and Homo sapiens chromosome 8, clone RP11-10A14 (AC022784.6) associated with the PPP1R3B genotype. In addition, genes enriched in transmembrane transport and phospholipid binding pathways were associated with the genotype. Conclusion: The rs4240624 variant in PPP1R3B has a major effect on the composition of gallbladder bile. Other transcripts in the same loci may be important mediators of the variant effect. (Hepatology Communications 2020;0:1-14).

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Genetic architecture of 11 abdominal organ traits derived from abdominal MRI using deep learning

Cited by 27 publications

References 115 publications

Genome-wide Association Study of Pancreatic Fat: The Multiethnic Cohort Adiposity Phenotype Study

Genome-wide Association Study of Pancreatic Fat: The Multiethnic Cohort Adiposity Phenotype Study

Large-scale analysis of iliopsoas muscle volumes in the UK Biobank

Protein Phosphatase 1 Regulatory Subunit 3B Genotype at rs4240624 Has a Major Effect on Gallbladder Bile Composition

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