Abstract：
OBJECTIVE: To test the hypothesis that liver-expressed antimicrobial peptide 2 (LEAP2) genetic variants might influence the susceptibility to human obesity.
METHODS: Using data from the UK Biobank, we identified independent LEAP2 gene single nucleotide polymorphisms (SNPs) and examined their associations with obesity traits and serum insulin-like growth factor-1 (IGF-1) concentration. These associations were evaluated for both individual SNPs and after combining them into a genetic risk score (GRSLEAP2) using linear and logistic regression models. Sex-stratified analyses were also conducted.
RESULTS: Five SNPs showed positive associations with obesity-related traits. rs57880964 was associated with body mass index (BMI) and waist-to-hip ratio adjusted for BMI (WHRadjBMI), in the total population and among women. Four independent SNPs were positively associated with higher serum IGF-1 concentrations in both men and women. GRSLEAP2 was associated with BMI and WHRadjBMI only in women and with serum IGF-1 concentration in both sexes.
CONCLUSIONS: These findings reveal sex-specific associations between key LEAP2 gene variants and several obesity traits, while also indicating a strong independent association of LEAP2 variants with serum IGF-1 concentration.
METHODS: Using data from the UK Biobank, we identified independent LEAP2 gene single nucleotide polymorphisms (SNPs) and examined their associations with obesity traits and serum insulin-like growth factor-1 (IGF-1) concentration. These associations were evaluated for both individual SNPs and after combining them into a genetic risk score (GRSLEAP2) using linear and logistic regression models. Sex-stratified analyses were also conducted.
RESULTS: Five SNPs showed positive associations with obesity-related traits. rs57880964 was associated with body mass index (BMI) and waist-to-hip ratio adjusted for BMI (WHRadjBMI), in the total population and among women. Four independent SNPs were positively associated with higher serum IGF-1 concentrations in both men and women. GRSLEAP2 was associated with BMI and WHRadjBMI only in women and with serum IGF-1 concentration in both sexes.
CONCLUSIONS: These findings reveal sex-specific associations between key LEAP2 gene variants and several obesity traits, while also indicating a strong independent association of LEAP2 variants with serum IGF-1 concentration.
摘要：
目的：验证肝脏表达的抗菌肽2（LEAP2）遗传变异可能影响人类肥胖易感性的假设。
方法：使用英国生物库的数据，我们鉴定了独立的LEAP2基因单核苷酸多态性(SNPs),并检测了它们与肥胖性状和血清胰岛素样生长因子-1(IGF-1)浓度的关联.使用线性和逻辑回归模型，对两个单独的SNP进行评估，并将其组合为遗传风险评分（GRSLEAP2）。还进行了性别分层分析。
结果：5个SNP与肥胖相关性状呈正相关。rs57880964与体重指数（BMI）和经BMI校正的腰臀比（WHRadjBMI）相关，在总人口和妇女中。在男性和女性中，四个独立的SNP与较高的血清IGF-1浓度呈正相关。GRSLEAP2仅与女性的BMI和WHRadjBMI相关，与男女血清IGF-1浓度相关。
结论：这些发现揭示了LEAP2关键基因变异体与几种肥胖特征之间的性别特异性关联，同时也表明LEAP2变体与血清IGF-1浓度之间存在强烈的独立关联。
方法：使用英国生物库的数据，我们鉴定了独立的LEAP2基因单核苷酸多态性(SNPs),并检测了它们与肥胖性状和血清胰岛素样生长因子-1(IGF-1)浓度的关联.使用线性和逻辑回归模型，对两个单独的SNP进行评估，并将其组合为遗传风险评分（GRSLEAP2）。还进行了性别分层分析。
结果：5个SNP与肥胖相关性状呈正相关。rs57880964与体重指数（BMI）和经BMI校正的腰臀比（WHRadjBMI）相关，在总人口和妇女中。在男性和女性中，四个独立的SNP与较高的血清IGF-1浓度呈正相关。GRSLEAP2仅与女性的BMI和WHRadjBMI相关，与男女血清IGF-1浓度相关。
结论：这些发现揭示了LEAP2关键基因变异体与几种肥胖特征之间的性别特异性关联，同时也表明LEAP2变体与血清IGF-1浓度之间存在强烈的独立关联。
