Genome-Wide Association Study of Body Fat Distribution identifies Novel Adiposity Loci and Sex-Specific Genetic Effects

Rask‐Andersen, Mathias; Karlsson, Torgny; Ek, WE; Johansson, Åsa

doi:10.1101/207498

Cited by 4 publications

(6 citation statements)

References 52 publications

(19 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The selective regions detected by XP-EHH showed a similar pattern to those found by F ST , XP-CLR, and log 2 (π ratio ). Overall, 40, 67, and 43 overlapping regions were detected by XP-EHH and F ST , XP-CLR, and log 2 (π ratio ), respectively (Supplementary Data [44][45].…”

Section: Resultsmentioning

confidence: 99%

“…As the main lipid storage depot, adipocytes play a crucial role in buffering the daily influx of dietary fat into circulation. In humans, body fat distribution is of clinical interest because of its links to multiple metabolic diseases 45 . Previous studies reported that fat stored in the trunk was more pathogenic than that stored in other compartments, and the accumulation of adipose tissue in the upper body (abdominal region) was more pathogenic than that in the lower body (gluteofemoral region) 46 .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Whole-body adipose tissue multi-omic analyses in sheep reveal molecular mechanisms underlying local adaptation to extreme environments

Wang

Jing

et al. 2023

Commun Biol

View full text Add to dashboard Cite

The fat tail of sheep is an important organ that has evolved to adapt to extreme environments. However, the genetic mechanisms underlying the fat tail phenotype remain poorly understood. Here, we characterize transcriptome and lipidome profiles and morphological changes in 250 adipose tissues from two thin-tailed and three fat-tailed sheep populations in summer and winter. We implement whole-genome selective sweep tests to identify genetic variants related to fat-tails. We identify a set of functional genes that show differential expression in the tail fat of fat-tailed and thin-tailed sheep in summer and winter. These genes are significantly enriched in pathways, such as lipid metabolism, extracellular matrix (ECM) remodeling, molecular transport, and inflammatory response. In contrast to thin-tailed sheep, tail fat from fat-tailed sheep show slighter changes in adipocyte size, ECM remodeling, and lipid metabolism, and had less inflammation in response to seasonal changes, indicating improved homeostasis. Whole-genome selective sweep tests identify genes involved in preadipocyte commitment (e.g., BMP2, PDGFD) and terminal adipogenic differentiation (e.g., VEGFA), which could contribute to enhanced adipocyte hyperplasia. Altogether, we establish a model of regulatory networks regulating adipose homeostasis in sheep tails. These findings improve our understanding of how adipose homeostasis is maintained, in response to extreme environments in animals.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Whole-body adipose tissue multi-omic analyses in sheep reveal molecular mechanisms underlying local adaptation to extreme environments

Wang

Jing

et al. 2023

Commun Biol

View full text Add to dashboard Cite

show abstract

“…Additional studies have confirmed the obesity-type 2 diabetes discordant genetic effects and the link to fat distribution and lipid metabolism, and genes that may represent targets for precision medicine approaches have been highlighted [82]. However, both fat distribution and the pathogenic effects by the adipose tissues are known to differ between sexes [83,84], and future studies stratifying by sex are therefore needed to increase the precision in prevention and treatment strategies for obesity [85].…”

Section: Genetic Subtyping In Obesity and Metabolismmentioning

confidence: 99%

Precision medicine in complex diseases—Molecular subgrouping for improved prediction and treatment stratification

et al. 2023

Self Cite

View full text Add to dashboard Cite

Complex diseases are caused by a combination of genetic, lifestyle, and environmental factors and comprise common noncommunicable diseases, including allergies, cardiovascular disease, and psychiatric and metabolic disorders. More than 25% of Europeans suffer from a complex disease, and together these diseases account for 70% of all deaths. The use of genomic, molecular, or imaging data to develop accurate diagnostic tools for treatment recommendations and preventive strategies, and for disease prognosis and prediction, is an important step toward precision medicine. However, for complex diseases, precision medicine is associated with several challenges. There is a significant heterogeneity between patients of a specific disease—both with regards to symptoms and underlying causal mechanisms—and the number of underlying genetic and nongenetic risk factors is often high. Here, we summarize precision medicine approaches for complex diseases and highlight the current breakthroughs as well as the challenges. We conclude that genomic‐based precision medicine has been used mainly for patients with highly penetrant monogenic disease forms, such as cardiomyopathies. However, for most complex diseases—including psychiatric disorders and allergies—available polygenic risk scores are more probabilistic than deterministic and have not yet been validated for clinical utility. However, subclassifying patients of a specific disease into discrete homogenous subtypes based on molecular or phenotypic data is a promising strategy for improving diagnosis, prediction, treatment, prevention, and prognosis. The availability of high‐throughput molecular technologies, together with large collections of health data and novel data‐driven approaches, offers promise toward improved individual health through precision medicine.

show abstract

“…We follow this discussion by talking about the role of the oestrogen receptors (ERs) in adipose tissues. We provide a brief discussion on what was learned through genome-wide association studies (GWAS) regarding how oestrogenregulated genes influence sex differences in body fat distribution [10]. We expand our discussion on the role sex plays in determining adipose tissue function by discussing the role sex chromosomes have in influencing adiposity [10,11].…”

Section: Introductionmentioning

confidence: 99%

“…We provide a brief discussion on what was learned through genome-wide association studies (GWAS) regarding how oestrogenregulated genes influence sex differences in body fat distribution [10]. We expand our discussion on the role sex plays in determining adipose tissue function by discussing the role sex chromosomes have in influencing adiposity [10,11]. Oestrogens also influence adipose tissue lineage and epigenetics as additional methods they impact metabolism.…”

Section: Introductionmentioning

confidence: 99%

The evolutionary impact and influence of oestrogens on adipose tissue structure and function

Bardhi

Palmer

Clegg

2023

Phil. Trans. R. Soc. B

View full text Add to dashboard Cite

Oestrogens are sex steroid hormones that have gained prominence over the years owing to their crucial roles in human health and reproduction functions which have been preserved throughout evolution. One of oestrogens actions, and the focus of this review, is their ability to determine adipose tissue distribution, function and adipose tissue ‘health’. Body fat distribution is sexually dimorphic, affecting males and females differently. These differences are also apparent in the development of the metabolic syndrome and other chronic conditions where oestrogens are critical. In this review, we summarize the different molecular mechanisms, pathways and resulting pathophysiology which are a result of oestrogens actions in and on adipose tissues. This article is part of a discussion meeting issue ‘Causes of obesity: theories, conjectures and evidence (Part I)’.

show abstract

Genome-Wide Association Study of Body Fat Distribution identifies Novel Adiposity Loci and Sex-Specific Genetic Effects

Cited by 4 publications

References 52 publications

Whole-body adipose tissue multi-omic analyses in sheep reveal molecular mechanisms underlying local adaptation to extreme environments

Whole-body adipose tissue multi-omic analyses in sheep reveal molecular mechanisms underlying local adaptation to extreme environments

Precision medicine in complex diseases—Molecular subgrouping for improved prediction and treatment stratification

The evolutionary impact and influence of oestrogens on adipose tissue structure and function

Contact Info

Product

Resources

About