Genomic Heritabilities and Correlations of 17 Traits Related to Obesity and Associated Conditions in the Japanese Population

Abstract

<jats:p>Over the past few decades, obesity has become a public health issue of global concern. Even though disparities exist between human populations, <jats:italic>e.g.</jats:italic>, 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.</jats:p>

Whole genome sequence association analysis of fasting glucose and fasting insulin levels in diverse cohorts from the NHLBI TOPMed program

“…This variant is rare overall, but observed frequently (EAF = 0.07) in the African ancestry population. This gene has previously been associated with BMI, which has moderate genetic correlation (previously estimated as ρ g = 0.48) with FI 20,21 . The expression of this gene is most commonly associated with variants as eQTLs in pancreas in GTEx 31 .…”

“…Near the APOB region a suggestively associated variant at rs478588 (P = 2.9 × 10 −9 ) has not previously identified (Supplementary Data 4). Variant rs478588 has robust associations with lipid traits 20 and significant parent-of-origin effects on metabolic traits 21 . Lipid traits have been studied for pleiotropy with glycemic traits but have been inconclusive with respect to APOB.…”

Whole Genome Sequence Association Analysis of Fasting Glucose and Fasting Insulin Levels in Diverse Cohorts from the NHLBI TOPMed Program

“…It is rare overall, but observed with low frequency (EAF=0.07) in the African population. This gene has previously been associated with BMI, which has moderate genetic correlation (previously estimated as ρ g =0.48) with FI 21; 22 . The expression of this gene is most commonly associated with variants as eQTLs in pancreas in GTEx 20 .…”