Genomic Heritabilities and Correlations of 17 Traits Related to Obesity and Associated Conditions in the Japanese Population
Genomic Heritabilities and Correlations of 17 Traits Related to Obesity and Associated Conditions in the Japanese Population
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DOI：
10.1534/g3.120.401242
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发表时间：
2020-07-01
影响因子：
2.6
通讯作者：
Nagasaki, Masao
中科院分区：
文献类型：
--
作者：
Gervais, Olivier;Ueno, Kazuko;Nagasaki, Masao
在过去的几十年里，肥胖已经成为全球关注的公共卫生问题。尽管人口之间存在差异，例如，尽管日本人的体重指数（BMI）较低，但肝脏脂肪含量较高，肥胖遗传学研究仍主要集中在欧洲血统的人群中，导致缺乏非欧洲人群的遗传数据。在这种情况下，本研究旨在通过检查参与东北医疗Megabank项目队列的18，889名个体的代表性样本，建立日本人群遗传属性的广泛图景。我们应用线性混合模型方法对17个与肥胖及相关疾病相关的性状进行了遗传力估计，以估计常见遗传变异所解释的遗传力以及每对性状之间的遗传相关。这些分析使我们能够量化健康指标的SNP遗传力，如BMI（0.248 +/- 0.032）和HDL胆固醇（0.324 +/- 0.031），并提供非相关个体中胱抑素C SNP遗传力的少数估计值之一（0.260 +/- 0.025）。我们讨论了日本人和欧洲血统的人之间的潜在差异，尿生物标志物和肥胖性状之间的遗传相关性，获得了大量的估计。例如，尿钾水平与体重，BMI，腰围和腰围与身高比之间的遗传相关性范围为0.290至0.559，远高于英国生物银行的相应估计值。
Over the past few decades, obesity has become a public health issue of global concern. Even though disparities exist between human populations,e.g., the higher liver fat content of the Japanese despite a lower body mass index (BMI), studies on the genetics of obesity still largely focus on populations of European descent, leading to a dearth of genetic data on non-European populations. In this context, this study aimed to establish a broad picture of the genetic attributes of the Japanese population, by examining a representative sample of 18,889 individuals participating in the Tohoku Medical Megabank Project cohort. We applied linear mixed model methods to 17 traits related to obesity and associated diseases to estimate the heritabilities explained by common genetic variants and the genetic correlations between each pair of traits. These analyses allowed us to quantify the SNP heritability of health indicators such as BMI (0.248 +/- 0.032) and HDL cholesterol (0.324 +/- 0.031), and to provide one of the few estimates of the SNP heritability of cystatin C in unrelated individuals (0.260 +/- 0.025). We discuss potential differences between the Japanese and people of European ancestry with respect to the genetic correlations between urinary biomarkers and adiposity traits, for which large estimates were obtained. For instance, the genetic correlations between urine potassium level and the values for weight, BMI, waist circumference, and waist-to-height ratio ranged from 0.290 to 0.559, much higher than the corresponding estimates in the UK Biobank.