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- Titel:
Machine Learning based histology phenotyping to investigate the epidemiologic and genetic basis of adipocyte morphology and cardiometabolic traits.
- Dokumenttyp:
- Article; Journal Article; Meta-Analysis; Research Support, Non-U.S. Gov't
- Autor(en):
- Glastonbury, Craig A; Pulit, Sara L; Honecker, Julius; Censin, Jenny C; Laber, Samantha; Yaghootkar, Hanieh; Rahmioglu, Nilufer; Pastel, Emilie; Kos, Katerina; Pitt, Andrew; Hudson, Michelle; Nellåker, Christoffer; Beer, Nicola L; Hauner, Hans; Becker, Christian M; Zondervan, Krina T; Frayling, Timothy M; Claussnitzer, Melina; Lindgren, Cecilia M
- Abstract:
- Genetic studies have recently highlighted the importance of fat distribution, as well as overall adiposity, in the pathogenesis of obesity-associated diseases. Using a large study (n = 1,288) from 4 independent cohorts, we aimed to investigate the relationship between mean adipocyte area and obesity-related traits, and identify genetic factors associated with adipocyte cell size. To perform the first large-scale study of automatic adipocyte phenotyping using both histological and genetic data, we developed a deep learning-based method, the Adipocyte U-Net, to rapidly derive mean adipocyte area estimates from histology images. We validate our method using three state-of-the-art approaches; CellProfiler, Adiposoft and floating adipocytes fractions, all run blindly on two external cohorts. We observe high concordance between our method and the state-of-the-art approaches (Adipocyte U-net vs. CellProfiler: R2visceral = 0.94, P < 2.2 × 10-16, R2subcutaneous = 0.91, P < 2.2 × 10-16), and faster run times (10,000 images: 6mins vs 3.5hrs). We applied the Adipocyte U-Net to 4 cohorts with histology, genetic, and phenotypic data (total N = 820). After meta-analysis, we found that mean adipocyte area positively correlated with body mass index (BMI) (Psubq = 8.13 × 10-69, βsubq = 0.45; Pvisc = 2.5 × 10-55, βvisc = 0.49; average R2 across cohorts = 0.49) and that adipocytes in subcutaneous depots are larger than their visceral counterparts (Pmeta = 9.8 × 10-7). Lastly, we performed the largest GWAS and subsequent meta-analysis of mean adipocyte area and intra-individual adipocyte variation (N = 820). Despite having twice the number of samples than any similar study, we found no genome-wide significant associations, suggesting that larger sample sizes and a homogenous collection of adipose tissue are likely needed to identify robust genetic associations.
- Zeitschriftentitel:
- PLoS Comput Biol
- Jahr:
- 2020
- Band / Volume:
- 16
- Heft / Issue:
- 8
- Volltext / DOI:
- doi:10.1371/journal.pcbi.1008044
- PubMed:
- http://view.ncbi.nlm.nih.gov/pubmed/32797044
- Print-ISSN:
- 1553-734X
- TUM Einrichtung:
- Else Kröner-Fresenius-Zentrum für Ernährungsmedizin - Klinik für Ernährungsmedizin
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