Identification of genetic loci affecting body mass index through interaction with multiple environmental factors using structured linear mixed model
Open Access
- 2 March 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Scientific Reports
- Vol. 11 (1), 1-11
- https://doi.org/10.1038/s41598-021-83684-1
Abstract
Multiple environmental factors could interact with a single genetic factor to affect disease phenotypes. We used Struct-LMM to identify genetic variants that interacted with environmental factors related to body mass index (BMI) using data from the Korea Association Resource. The following factors were investigated: alcohol consumption, education, physical activity metabolic equivalent of task (PAMET), income, total calorie intake, protein intake, carbohydrate intake, and smoking status. Initial analysis identified 7 potential single nucleotide polymorphisms (SNPs) that interacted with the environmental factors (P value < 5.00 × 10−6). Of the 8 environmental factors, PAMET score was excluded for further analysis since it had an average Bayes Factor (BF) value < 1 (BF = 0.88). Interaction analysis using 7 environmental factors identified 11 SNPs (P value < 5.00 × 10−6). Of these, rs2391331 had the most significant interaction (P value = 7.27 × 10−9) and was located within the intron of EFNB2 (Chr 13). In addition, the gene-based genome-wide association study verified EFNB2 gene significantly interacting with 7 environmental factors (P value = 5.03 × 10−10). BF analysis indicated that most environmental factors, except carbohydrate intake, contributed to the interaction of rs2391331 on BMI. Although the replication of the results in other cohorts is warranted, these findings proved the usefulness of Struct-LMM to identify the gene–environment interaction affecting disease.Funding Information
- National Research Foundation of Korea (2019M3E5D3073365)
This publication has 45 references indexed in Scilit:
- Gene × Physical Activity Interactions in Obesity: Combined Analysis of 111,421 Individuals of European AncestryPLoS Genetics, 2013
- Gene-environment interactions and obesity traits among postmenopausal African-American and Hispanic women in the Women’s Health Initiative SHARe StudyHuman Genetics, 2012
- Active Smoking and Risk of Metabolic Syndrome: A Meta-Analysis of Prospective StudiesPLOS ONE, 2012
- Sleep Duration and Body Mass Index in Twins: A Gene-Environment InteractionSleep, 2012
- Physical Activity Attenuates the Influence of FTO Variants on Obesity Risk: A Meta-Analysis of 218,166 Adults and 19,268 ChildrenPLoS Medicine, 2011
- Interaction of FTO and Physical Activity Level on Adiposity in African‐American and European‐American Adults: The ARIC StudyObesity, 2011
- Emerging disparities in overweight by educational attainment in Chinese adults (1989–2006)International Journal of Obesity, 2011
- A Dose-Response Relationship between Types of Physical Activity and DistressJournal of Korean Medical Science, 2008
- Replicating genotype–phenotype associationsNature, 2007
- Alcohol consumption as a risk factor for high blood pressure. Munich Blood Pressure Study.Hypertension, 1984