Direct-to-Consumer Genetic Test and Lifestyle Questionnaire Analysis of Body Mass Index and Body Fat Percentage in a Large Korean Population

Research Article

J Dis Markers. 2023; 8(1): 1051.

Direct-to-Consumer Genetic Test and Lifestyle Questionnaire Analysis of Body Mass Index and Body Fat Percentage in a Large Korean Population

Hyo-Eun Kim1, Kyung Mi Park3, Dasom Lee1,2, So-Ra Lee1, Sang-Woon Kim1, Tae Soon Hwang1,2 and Kyung-Won Hong1,2*

1Healthcare Technology, Theragen Health Co., Ltd., Pangyoyeok-ro 240, Seongnam-si, 13493, Republic of Korea

2Healthcare Technology, Theragen Bio Co., Ltd., Pangyoyeok-ro 240, Seongnam-si, 13493, Republic of Korea

3Herbalife Korea Co., Ltd., 706, Nonhyeon-ro, Gangnam-gu, Seoul, 06052, Republic of Korea

*Corresponding author: Kyung-Won HongHealthcare Technology, Theragen Bio Co., Ltd., Pangyoyeok-ro 240, Seongnam-si, 13493, Republic of Korea Tel.: +82-31-288-1288, Fax: +82-31-288-1295 E-mail: kyungwon.hong@theragenbio.com

Received: January 17, 2023; Accepted: February 13, 2023; Published: February 20, 2023

Abstract

Background: Direct-to-Consumer (DTC) genetic testing provides genetic risk to consumers and motivates consumers to take care of their own customized health care. In 2018, we developed and provided a DTC genetic testing service (GENESTART™) in collaboration with Herbalife Korea Co. Ltd.

Methods: The analyzed dataset consisted of the body fat percentage (BFP), body mass index (BMI), 31 genetic polymorphism genotypes, and responses to 19 questionnaire items of 24,447 individuals. The genetic main effects for BFP and BMI were examined by linear regression analysis, and the interaction effects were examined using a generalized linear model that controlled age and sex as covariates.

Results: In the case of BFP, the sample average was 31.47% overall, 24.76% for men, and 32.79% for women, showing that men had an average BFP that was 8 percentage points lower than that of women. The average BMI was 25.38 overall, 26.45 for men, and 25.17 for women, showing that men had an average BMI of 1.2 kg/m2 higher than that of women. The FTO and MC4R genes, well-known obesity markers, showed a significant correlation with both phenotypes, and the BDNF gene, which is related to stress obesity, showed a highly significant association with BMI but only a weak association with BFP. Among the remaining genes, TRIB1, ABCA1, MYL2, G6PC, GCKR, GLIS3, CYP17A1, HECTD4, and NT5C2 genes showed significant associations with the obesity-related phenotypes. In this study, we found four interaction results for BFP (ABO and fruits, CYP1A2 and sugary foods, FTO and muscle exercise, MC4R and vitamins) and five interactions for BMI (MC4R and proteins, CSK and fruits, MC4R and calcium, DGKB and calcium, CSK and water).

Conclusions: This study is expected to enable the provision of personalized and accurate solutions for BFP and BMI management to customers who have undergone genetic testing.

Keywords: Direct-to-consumer genetic testing; DTC; Interaction; Body fat percentage; Body mass index

Abbreviations: DTC: Direct-to-Consumer; BFC: Body Fat Percentage; BMI: Body Mass Index; SNP: Single Nucleotide Polymorphism

Introduction

After the Human Genome Project, genetic variations were discovered in the human genome [1]. dvancing genotyping technology enhanced the large-scale genome-wide association studies for each disease or phenotype [2]. The genetic markers for each disease or phenotype were discovered [3], and several companies (such as 23 and Me and Pathway Genomics) began to offer Direct-to-Consumer (DTC) genetic testing to check genetic vulnerability by testing genetic markers. In these genetic testing services, customers directly collect DNA test samples with a buccal swab or saliva kit and send them to the company [4]. The companies provide genetic test results to customers as well as customized solutions for those with vulnerable genotypes.

In line with the global DTC genetic testing trend, the Bioethics and Safety Act was amended in Korea to improve the DTC genetic testing regulations. In 2016, the Korean Ministry of Health and Welfare allowed domestic DTC services to test a total of 46 genetic markers of 12 phenotypes [4]. In accordance with these regulatory changes, we (Theragen Bio Co. Ltd.) also provided a DTC genetic testing service under the brand name GENESTART™ through collaboration with a functional health food company called Herbalife Korea [https://www.genestart.co.kr/].

The purpose of DTC genetic testing is to inform consumers of their genetic risk and motivate them to take care of their own customized health care. In particular, the GENESTART genetic test mainly aims to identify genetic factors related to obesity and metabolic syndrome. In this study, we examined the association between GENESTART results and obesity-related factors (BFP and BMI) and their interactions with lifestyle habits.

Methods

Samples & Questionnaires

The data of the study population were obtained via the DTC service through Herbalife Korea after confirming the content of genetic testing and the research application. This study was approved by the institutional review board of Theragen Etex Bio Institute (IRB No. 700062-20180905-JR-006-01). The participants collected buccal swab samples and answered the self-reported questionnaires. All the data used for statistical analysis were obtained from the 19 question items about nutrition intake from the self-administered health assessment (Supplementary Table 1). In addition, we provided a food intake guide to increase the accuracy of the survey responses (Supplementary Figure 1).

Genotyping

Buccal swab samples for genotyping were collected using a Buccal DNA Collector (Theragen Bio Co. Ltd, Korea). DNA was extracted by the Buccal DNA Collector using the Exgene™ Tissue SV kit (Gene All Biotechnology Co., Ltd., Seoul, Korea) and genotyped at Theragen Bio using a Quant Studio™ 12K Flex Open Array genotyping plate, custom format 64 (Thermo Fisher, Waltham, MA, USA) according to the manufacturer’s recommendation. Analysis of the genotyping results was performed using Quant Studio™ 12K Flex Real-Time PCR Software (Thermo Fisher, Waltham, MA, USA).

Statistical Analysis

To determine the strength of the relationship between the variables, a statistical correlation study was performed using correlation analysis with PASW Statistics (SPSS Inc., Hong Kong). The data are presented as mean ± SD (continuous variables) or as a percentage (categorical variables). We performed statistical analysis, including multiple linear regression, ANOVA (one-way and two-way), and the chisquared test. The multiple linear regression models were performed between SNP genotypes and BMI or BFP adjusted for age and sex.

We conducted 20 lifestyle-related surveys, as shown in Supplementary Table 1, to provide suggestions for lifestyle improvements to customers undergoing GENESTART genetic testing. The interaction analyses were conducted using the generalized linear model below.

BFP ~ Age×ßAGE+Sex×ßSEX+G×ßG+Q×ßQ+GQ×ßGQ

BMI ~ Age×ßAGE+Sex×ßSEX+G×ßG+Q×ßQ+GQ×ßGQ

Where the ßs are the effect sizes of age, sex, genotype (G), questionnaire (Q), and the interaction effect size (GQ). P-values less than 0.05 were considered statistically significant.

Results

Population Characteristics

The study population characteristics are described in (Table 1). A total of 24,447 people who received the GENESTART service were analyzed as the subjects of the study. The average age of the subjects was 45.38 ± 11.73 years old, and the age ranged from 20 to 70 years. Among the subjects, approximately 83.5% (20,425) were women and the remaining 16.7% (4,022) were men.

The average BFP was 31.47% overall, 24.76% for men, and 32.79% for women, showing that men had 8 percentage points lower BFP than women on average. Further broken down by age, both men and women in their 20s and 30s had the highest BFP, though it decreased for both groups beginning in their 40s. The average BMI was 25.38 for the entire sample, 26.45 for men, and 25.17 for women, showing that men had an average BMI of 1.2 kg/m2 higher than that of women.

Genetic Association between DTC Genes and BMI or BF

We listed the genetic markers and described the association between the target genetic markers and the obesity-related phenotypes (BFP and BMI) in Table 2 (5–35). The FTO and MC4R genes—well-known obesity markers—showed a significant correlation with both phenotypes, and the BDNF gene, a gene related to stress obesity, showed a highly significant association with BMI but only a weak correlation with BFP.

Among the triglyceride genes, the TRIB1 gene was observed to have a significant association with increasing BFP. Also, the ABCA1 and MYL2 genes among cholesterol-related genes; G6PC, GCKR, and GLIS3 genes among the blood sugar–related genes; and CYP17A1, HECTD4, and NT5C2 genes among the blood sugar-related genes showed significant associations with obesity-related phenotypes.

Gene and Questionnaire Interaction for BMI and BFP

We analyzed the effect of the interaction between the genotypes of individuals identified through GENESTART and the survey results of BFP and BMI. Of the 30 genetic markers, 21 showed a significant interaction (Supplementary Table 2). Each interaction was further analyzed using a graph (Supplementary Figure 2 & 3). The statistically significant interactions that showed obvious changes when graphed were summarized in (Table 3), and the interactions are described in (Figure 1 (BFP) and 2) (BMI).

Citation:Kim HE et al. Direct-to-Consumer Genetic Test and Lifestyle Questionnaire Analysis of Body Mass Index and Body Fat Percentage in a Large Korean Population. J Dis Markers. 2023; 8(1): 1051.