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. 2022 Oct 6;23(19):11889.
doi: 10.3390/ijms231911889.

Lifestage Sex-Specific Genetic Effects on Metabolic Disorders in an Adult Population in Korea: The Korean Genome and Epidemiology Study

Young-Sang Kim  1 , Yon Chul Park  2   3 , Ja-Eun Choi  4 , Jae-Min Park  5 , Kunhee Han  6 , Kwangyoon Kim  7   8 , Bom-Taeck Kim  7 , Kyung-Won Hong  2
Affiliations

Lifestage Sex-Specific Genetic Effects on Metabolic Disorders in an Adult Population in Korea: The Korean Genome and Epidemiology Study

Young-Sang Kim et al. Int J Mol Sci. .

Abstract

Although many genome-wide association studies (GWASs) have evaluated the association with metabolic disorders, the current study is the first attempt to analyze the genetic risk factors for various metabolic disorders according to sex and age groups of the life course in Korean adults. A total population of 50,808 people were included in this GWAS. The genetic traits for eight metabolic phenotypes were investigated in peri-, and postmenopausal women compared to a younger group or men of corresponding age groups. The metabolic phenotypes include general obesity, abdominal obesity, hypertension, type 2 diabetes, hypercholesterolemia, hypertriglyceridemia, hypo-high-density lipoprotein cholesterolemia, and metabolic syndrome. In the total participants, GWAS results for eight metabolic phenotypes found 101 significant loci. Of these, 15 loci were the first reported to be associated with the risk of metabolic disorder. Interestingly, some of the significant loci presented the association with the various phenotypes, which presented when there was a correlation between phenotypes. In addition, we analyzed divided by gender and age (young adult, peri-menopausal group, older adult), and specifically identified specific loci in peri-menopausal women. Meanwhile, several genetic factors associated with metabolic disorders were newly reported in our study. In particular, several genes were significantly associated with one of the metabolic phenotypes in only a single specific group. These findings suggest that menopausal transition rather than aging itself potentiates the influence of genetic risks on metabolic disorders. In addition, some genetic loci with low frequencies may play a role in the metabolic disturbances in a specific sex and age group. The genetic traits derived from our study may contribute to understanding the genetic risk factors for metabolic disorders in the Korean population.

Keywords: genome-wide association studies; metabolic disorders; perimenopause; postmenopause; premenopause.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Flow chart of the study. The perimenopausal age group (45–55 years) includes perimenopausal women and perimenopause-corresponding men. KoGES, Korean Genome and Epidemiology Study; WC, waist circumference; BMI, body mass index.
Figure 2
Figure 2
Manhattan plots of each GWAS p-value. The X-axis is the number of chromosomes, and the Y-axis is the minus Log10(P). Each locus was numbered using the ‘L’ character, which indicated the significant locus. The same ‘L’ characters and numbering between Manhattan and Miami plots indicated the same locus, which implied that the locus was similarly associated with the phenotype in both the total group and subgroup. We extracted the most significant SNP (top signal) for each locus.
Figure 2
Figure 2
Manhattan plots of each GWAS p-value. The X-axis is the number of chromosomes, and the Y-axis is the minus Log10(P). Each locus was numbered using the ‘L’ character, which indicated the significant locus. The same ‘L’ characters and numbering between Manhattan and Miami plots indicated the same locus, which implied that the locus was similarly associated with the phenotype in both the total group and subgroup. We extracted the most significant SNP (top signal) for each locus.
Figure 3
Figure 3
Heat-map analysis based on genome-wide association study results. A red mark means an association with a p-value of less than 5 × 10−8, and black or gray means a case that shows a p-value between 0.05 and 5 × 10−8, although not 5 × 10−8 significance. (A) shows the significant results confirmed in the GWAS analysis using the entire sample, (B) shows the results for the male group, and (C) shows the results for the female group.
See this image and copyright information in PMC

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