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内脏、腹部皮下和臀股部脂肪蓄积的遗传基础。

Inherited basis of visceral, abdominal subcutaneous and gluteofemoral fat depots.

机构信息

Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Center for Genomic Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.

出版信息

Nat Commun. 2022 Jun 30;13(1):3771. doi: 10.1038/s41467-022-30931-2.

DOI:10.1038/s41467-022-30931-2
PMID:35773277
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9247093/
Abstract

For any given level of overall adiposity, individuals vary considerably in fat distribution. The inherited basis of fat distribution in the general population is not fully understood. Here, we study up to 38,965 UK Biobank participants with MRI-derived visceral (VAT), abdominal subcutaneous (ASAT), and gluteofemoral (GFAT) adipose tissue volumes. Because these fat depot volumes are highly correlated with BMI, we additionally study six local adiposity traits: VAT adjusted for BMI and height (VATadj), ASATadj, GFATadj, VAT/ASAT, VAT/GFAT, and ASAT/GFAT. We identify 250 independent common variants (39 newly-identified) associated with at least one trait, with many associations more pronounced in female participants. Rare variant association studies extend prior evidence for PDE3B as an important modulator of fat distribution. Local adiposity traits (1) highlight depot-specific genetic architecture and (2) enable construction of depot-specific polygenic scores that have divergent associations with type 2 diabetes and coronary artery disease. These results - using MRI-derived, BMI-independent measures of local adiposity - confirm fat distribution as a highly heritable trait with important implications for cardiometabolic health outcomes.

摘要

对于任何给定的总体肥胖水平，个体的脂肪分布差异很大。一般人群中脂肪分布的遗传基础尚未完全了解。在这里，我们研究了多达 38965 名英国生物银行参与者的 MRI 衍生内脏（VAT）、腹部皮下（ASAT）和臀股（GFAT）脂肪组织体积。由于这些脂肪库体积与 BMI 高度相关，我们还研究了六个局部肥胖特征：BMI 和身高调整后的 VAT（VATadj）、ASATadj、GFATadj、VAT/ASAT、VAT/GFAT 和 ASAT/GFAT。我们确定了 250 个与至少一个特征相关的独立常见变异（39 个新发现），许多关联在女性参与者中更为明显。罕见变异关联研究扩展了 PDE3B 作为脂肪分布重要调节剂的先前证据。局部肥胖特征（1）突出了储存部位特异性的遗传结构，（2）使构建储存部位特异性多基因评分成为可能，这些评分与 2 型糖尿病和冠心病的相关性不同。这些结果 - 使用 MRI 衍生的、与 BMI 无关的局部肥胖测量值 - 证实了脂肪分布是一种高度遗传的特征，对心血管代谢健康结果有重要影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0aa6/9247093/5bd5309122b9/41467_2022_30931_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0aa6/9247093/d16c62a5b911/41467_2022_30931_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0aa6/9247093/2d261d586926/41467_2022_30931_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0aa6/9247093/d32cc689ec65/41467_2022_30931_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0aa6/9247093/756f750726af/41467_2022_30931_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0aa6/9247093/5bd5309122b9/41467_2022_30931_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0aa6/9247093/d16c62a5b911/41467_2022_30931_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0aa6/9247093/3a1537a4b347/41467_2022_30931_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0aa6/9247093/b2f20e75d78b/41467_2022_30931_Fig3_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0aa6/9247093/d32cc689ec65/41467_2022_30931_Fig5_HTML.jpg
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