Department of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ, USA.
BIO5 Institute, University of Arizona, Arizona, AZ, USA.
Eur J Hum Genet. 2023 Mar;31(3):338-344. doi: 10.1038/s41431-022-01231-6. Epub 2022 Nov 16.
Lipedema is a common disorder characterized by excessive deposition of subcutaneous adipose tissue (SAT) in the legs, hips, and buttocks, mainly occurring in adult women. Although it appears to be heritable, no specific genes have yet been identified. To identify potential genetic risk factors for lipedema, we used bioelectrical impedance analysis and anthropometric data from the UK Biobank to identify women with and without a lipedema phenotype. Specifically, we identified women with both a high percentage of fat in the lower limbs and a relatively small waist, adjusting for hip circumference. We performed a genome-wide association study (GWAS) for this phenotype, and performed multiple sensitivity GWAS. In an independent case/control study of lipedema based on strict clinical criteria, we attempted to replicate our top hits. We identified 18 significant loci (p < 5 × 10), several of which have previously been identified in GWAS of waist-to-hip ratio with larger effects in women. Two loci (VEGFA and GRB14-COBLL1) were significantly associated with lipedema in the independent replication study. Follow-up analyses suggest an enrichment of genes expressed in blood vessels and adipose tissue, among other tissues. Our findings provide a starting point towards better understanding the genetic and physiological basis of lipedema.
脂肪营养不良是一种常见的疾病，其特征是下肢、臀部和臀部的皮下脂肪组织（SAT）过度沉积，主要发生在成年女性中。尽管它似乎具有遗传性，但尚未确定特定的基因。为了确定脂肪营养不良的潜在遗传风险因素，我们使用英国生物银行的生物电阻抗分析和人体测量数据，确定了有和没有脂肪营养不良表型的女性。具体来说，我们确定了下肢脂肪百分比高且腰围相对较小的女性，同时调整了臀围。我们对该表型进行了全基因组关联研究（GWAS），并进行了多次敏感性 GWAS。在一项基于严格临床标准的脂肪营养不良独立病例对照研究中，我们试图复制我们的顶级发现。我们确定了 18 个显著的位点（p<5×10），其中一些先前在腰臀比的 GWAS 中被发现，对女性的影响更大。两个位点（VEGFA 和 GRB14-COBLL1）在独立的复制研究中与脂肪营养不良显著相关。后续分析表明，血管和脂肪组织等组织中表达的基因富集。我们的发现为更好地理解脂肪营养不良的遗传和生理基础提供了一个起点。
