# Genetic predisposition to elevated BMI and adult asthma phenotypes in a Japanese population

**Authors:** Yohei Yatagai, Hisayuki Oshima, Yu Abe, Haruna Kitazawa, Hironori Masuko, Takashi Naito, Takefumi Saito, Tomomitsu Hirota, Mayumi Tamari, Emiko Noguchi, Tohru Sakamoto, Nobuyuki Hizawa, Muhammad Salman Bashir, Muhammad Salman Bashir, Muhammad Salman Bashir

PMC · DOI: 10.1371/journal.pone.0340728 · 2026-01-29

## TL;DR

This study explores how genetic factors linked to higher BMI influence asthma types in Japanese adults, revealing genetic diversity in asthma subgroups.

## Contribution

The study identifies distinct asthma subtypes influenced by BMI-related genetic variants in a Japanese population.

## Key findings

- Asthma patients had higher BMI than healthy individuals, but no significant difference in BMI-GRS was found between the groups.
- Cluster analysis revealed six asthma phenotypes, including two overweight/obese clusters and four non-obese clusters with varying BMI-GRS.
- Genetic variants associated with BMI contribute to specific asthma subtypes, highlighting genetic heterogeneity in adult asthma.

## Abstract

Obesity is a well-established risk factor for asthma, with genetic factors influencing both conditions. This study investigates the impact of genetic predisposition to increased body mass index (BMI) on adult asthma phenotypes. We recruited 1532 non-asthmatic healthy individuals and 779 adult asthma patients to assess the relationship between BMI-related genetic risk scores (BMI-GRS) and asthma. Among the 85 single nucleotide polymorphisms (SNPs) previously associated with BMI in Japanese populations, significant associations with BMI were confirmed for 6 SNPs in the healthy individuals. Using these, BMI-GRS was calculated for both groups. While asthma patients had higher BMI than healthy individuals (p = 0.004), no significant difference in BMI-GRS was observed between the groups (p = 0.56). A cluster analysis identified six distinct phenotypes of adult asthma patients: two overweight/obese clusters (one with elevated BMI-GRS, one without) and four non-obese clusters (with one showing significantly elevated BMI-GRS). This study demonstrates a genetic heterogeneity in the phenotype of adult asthma among a Japanese population, showing that genetic variants associated with BMI contribute to specific subtypes of asthma. Prospective longitudinal studies are essential to delineate the interactions between genetic predisposition, elevated BMI, subsequent changes in adiposity, and the evolution of asthma phenotypes, which would facilitate the development of mechanism-based therapeutic strategies tailored to genetically-defined patient subgroups.

## Linked entities

- **Diseases:** asthma (MONDO:0004979)

## Full-text entities

- **Genes:** TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, LINC01122 (long intergenic non-protein coding RNA 1122) [NCBI Gene 400955] {aka LINC01793, uc.52, uc.53, uc.54}, Stk33 (serine/threonine kinase 33) [NCBI Gene 117229] {aka 4921505G21Rik}, ALK (ALK receptor tyrosine kinase) [NCBI Gene 238] {aka ALK1, CD246, NBLST3}, TMEM18 (transmembrane protein 18) [NCBI Gene 129787] {aka lncND}, ADIPOQ (adiponectin, C1Q and collagen domain containing) [NCBI Gene 9370] {aka ACDC, ACRP30, ADIPQTL1, ADPN, APM-1, APM1}, PCSK1 (proprotein convertase subtilisin/kexin type 1) [NCBI Gene 5122] {aka BMIQ12, NEC1, PC1, PC1/3, PC3, SPC3}, STK33 (serine/threonine kinase 33) [NCBI Gene 65975] {aka SPGF93}, ERAP1 (endoplasmic reticulum aminopeptidase 1) [NCBI Gene 51752] {aka A-LAP, ALAP, APPILS, ARTS-1, ARTS1, ERAAP}, IGHE (immunoglobulin heavy constant epsilon) [NCBI Gene 3497] {aka IgE}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, GPR75 (G protein-coupled receptor 75) [NCBI Gene 10936] {aka GPRchr2, WI31133}, FTO (FTO alpha-ketoglutarate dependent dioxygenase) [NCBI Gene 79068] {aka ALKBH9, BMIQ14, GDFD, IFEX9}, LEP (leptin) [NCBI Gene 3952] {aka LEPD, OB, OBS}, PSME4 (proteasome activator subunit 4) [NCBI Gene 23198] {aka Blm10, PA200, hBlm10}
- **Diseases:** adiposity (MESH:D018205), weight gain (MESH:D015430), airway inflammation (MESH:D007249), insulin resistance (MESH:D007333), Asthmatic (MESH:D013224), airflow limitation (MESH:D029424), metabolic dysregulation (MESH:D021081), dysbiosis (MESH:D064806), overweight (MESH:D050177), ORCID iD (MESH:C535742), atopy (MESH:C564133), Asthma (MESH:D001249), endotoxemia (MESH:D019446), atopic (MESH:C566404), OA (MESH:D010003), Obesity (MESH:D009765), systemic (MESH:D015619), dyspnea (MESH:D004417)
- **Chemicals:** ADMA (MESH:C018524), PONE-D-25-02383R1 (-), Nitric Oxide (MESH:D009569)
- **Species:** Homo sapiens (human, species) [taxon 9606], gut metagenome (species) [taxon 749906]
- **Mutations:** serine/threonine, rs4929949, rs939584, rs10208649, rs16937956, rs11642015, rs1006257, rs10197655

## Figures

11 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12854457/full.md

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Source: https://tomesphere.com/paper/PMC12854457