<br>BMI 多基因评分对减肥效果和全基因组关联分析的影响,International Journal of Obesity

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BMI 多基因评分对减肥效果和全基因组关联分析的影响
International Journal of Obesity ( IF 4.2 ) Pub Date : 2024-01-24 , DOI: 10.1038/s41366-024-01470-1
Hassan S Dashti _{1,

2,

3,

4} , Frank A J L Scheer _{2,

4,

5} , Richa Saxena _{1,

2,

3,

4} , Marta Garaulet _{5,

6,

7}

Affiliation

背景

虽然环境因素在减肥效果中发挥着重要作用，但遗传因素也可能影响减肥的成功。我们检查了 BMI 的全基因组多基因评分是否与减肥效果相关，旨在识别与减肥相关的常见遗传变异。

方法

ONTIME 研究的参与者（ n = 1210）遵循统一的多模式行为减肥干预措施。我们首先测试了较高 BMI 的全基因组多基因评分与减肥效果（总体重减轻、体重减轻率和减重）之间的关联。然后，我们在 ONTIME 研究中进行了减肥全基因组关联研究 (GWAS)，并与早期研究进行了最大的减肥荟萃分析 ( n = 3056)。最后，我们在 ONTIME 研究中对其他减肥结果和相关因素进行了探索性 GWAS。

结果

我们发现，多基因评分中的每个标准差增量都与体重减轻率的降低相关（95% CI）= -0.04（-0.06，-0.01； P = 3.7×10 ^-03 ）并且与更高的损耗相关按治疗持续时间调整后。在之前的 GWAS 减肥研究荟萃分析中，没有发现任何关联达到全基因组显着性。然而，ONTIME 研究中的关联显示的效果与已发表的 rs545936 ( MIR486/NKX6.3/ANK1 )（先前提到的减肥位点）的研究一致。在荟萃分析中，次要 A 等位基因的每个拷贝与治疗第五周时 0.12 (0.03) kg/m ²较高的 BMI 相关 ( P = 3.9 × 10 ^-06 )。在ONTIME研究中，我们还在与脂肪分解、体重和代谢调节有关的基因附近鉴定了两个全基因组显着的（ P < 5×10 ^-08 ）体重减轻率位点： NFIP1 / SPRY4 / FGF1附近的rs146905606；和LSAMP附近的 rs151313458 。

结论

我们的研究结果预计将有助于开发基于遗传学的个性化减肥方法。

临床试验注册

肥胖、营养遗传学、时机和地中海（ONTIME；clinicaltrials.gov：NCT02829619）研究。

"点击查看英文标题和摘要"

Impact of polygenic score for BMI on weight loss effectiveness and genome-wide association analysis

Background

While environmental factors play an important role in weight loss effectiveness, genetics may also influence its success. We examined whether a genome-wide polygenic score for BMI was associated with weight loss effectiveness and aimed to identify common genetic variants associated with weight loss.

Methods

Participants in the ONTIME study (n = 1210) followed a uniform, multimodal behavioral weight-loss intervention. We first tested associations between a genome-wide polygenic score for higher BMI and weight loss effectiveness (total weight loss, rate of weight loss, and attrition). We then conducted a genome-wide association study (GWAS) for weight loss in the ONTIME study and performed the largest weight loss meta-analysis with earlier studies (n = 3056). Lastly, we ran exploratory GWAS in the ONTIME study for other weight loss outcomes and related factors.

Results

We found that each standard deviation increment in the polygenic score was associated with a decrease in the rate of weight loss Beta (95% CI) = −0.04 (−0.06, −0.01; P = 3.7×10⁻⁰³) and with higher attrition after adjusting by treatment duration. No associations reached genome-wide significance in meta-analysis with previous GWAS studies for weight loss. However, associations in the ONTIME study showed effects consistent with published studies for rs545936 (MIR486/NKX6.3/ANK1), a previously noted weight loss locus. In the meta-analysis, each copy of the minor A allele was associated with 0.12 (0.03) kg/m² higher BMI at week five of treatment (P = 3.9 × 10⁻⁰⁶). In the ONTIME study, we also identified two genome-wide significant (P < 5×10⁻⁰⁸) loci for the rate of weight loss near genes implicated in lipolysis, body weight, and metabolic regulation: rs146905606 near NFIP1/SPRY4/FGF1; and rs151313458 near LSAMP.