TY - JOUR
T1 - Genome-wide gene by environment interaction analysis identifies common SNPs at 17q21.2 that are associated with increased body mass index only among asthmatics
AU - Wang, Leyao
AU - Murk, William
AU - DeWan, Andrew T.
N1 - Funding Information:
This work was supported by a cooperative agreement from the United States Air Force/AFMC [Award No. FA8650-13-2-6371]. http://www.afmc.af. mil/. Dr. Leyao Wang is supported by the NIH/NIAID Ruth L. Kirschstein National Research Service Award (NRSA) Individual Postdoctoral Fellowship (F32) [Award No. 1F32AI114097-01A1]. http://www.niaid. nih.gov/. William Murk is supported by a Doctoral Foreign Study Award from the Canadian Institutes of Health Research [Award No. DFS – 129311]. http:// www.cihr-irsc.gc.ca/e/37788.html/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. MESA and the MESA SHARe project are conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with MESA investigators. Support for MESA is provided by contracts N01-HC-95159, N01-HC-95160, N01-HC- 95161, N01-HC-95162, N01- HC-95163, N01-HC- 95164, N01-HC-95165, N01-HC-95166, N01-HC- 95167, N01-HC-95168, N01-HC-95169 and CTSA UL1-RR-024156. The Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air) is supported by the U.S. Environmental Protection Agency (EPA) under Science to Achieve Results (STAR) Program Grant # RD831697. The Framingham Heart Study is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with Boston University (Contract No. N01-HC-25195). Funding for SHARe genotyping was provided by NHLBI Contract N02-HL- 64278. SHARe Illumina genotyping was provided under an agreement between Illumina and Boston University. This manuscript was not prepared in collaboration with investigators of the MESA, MESA Air or Framingham Heart Study and does not necessarily reflect the opinions or views of those studies and funding agencies and no official endorsement should be inferred. We would like to thank Dr. Michael Bracken and Dr. Josephine Hoh (both from the Yale School of Public Health, New Haven, Connecticut) and Dr. Wenan Chen (Mayo Clinic Department of Health Sciences Research, Rochester, Minnesota) for their helpful comments and suggestions on the analysis and the manuscript.
Publisher Copyright:
© 2015 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - Asthmatics have an increased risk of being overweight/obese. Although the underlying mechanisms of this are unclear, genetic factors are believed to play an essential role. To identify common genetic variants that are associated with asthma-related BMI increase, we performed a genome-wide gene by environment (asthma) interaction analysis for the outcome of BMI in the Multi-Ethnic Study of Atherosclerosis (MESA) study (N = 2474 Caucasians, 257 asthmatics), and replicated findings in the Framingham Heart Study (FHS) offspring cohort (N = 1408 Caucasians, 382 asthmatics). The replicable tagging SNP, rs2107212, was further examined in stratified analyses. Seven SNPs clustered in 17q21.2 were identified to be associated with higher BMI among asthmatics (interaction p < 5×10-7 in MESA and p < 0.05 in FHS). In both MESA and FHS asthmatics, subjects carrying the A allele on rs2107212 had significantly higher odds of obesity than non-carriers, which was not the case for non-asthmatics.We further examined BMI change subsequent to asthma diagnosis over a period of 26 years in FHS and demonstrated greater BMI increase among asthmatics compared to non-asthmatics. Asthmatics carrying the A allele at rs2107212 had significantly greater net BMI increase over the 26-year period compared to non-asthmatics. In this study, we found that common genetic variants on 17q21.2 are associated with postasthma BMI increase among Caucasians. This finding will help elucidate pathways involved in the comorbidity of asthma and obesity.
AB - Asthmatics have an increased risk of being overweight/obese. Although the underlying mechanisms of this are unclear, genetic factors are believed to play an essential role. To identify common genetic variants that are associated with asthma-related BMI increase, we performed a genome-wide gene by environment (asthma) interaction analysis for the outcome of BMI in the Multi-Ethnic Study of Atherosclerosis (MESA) study (N = 2474 Caucasians, 257 asthmatics), and replicated findings in the Framingham Heart Study (FHS) offspring cohort (N = 1408 Caucasians, 382 asthmatics). The replicable tagging SNP, rs2107212, was further examined in stratified analyses. Seven SNPs clustered in 17q21.2 were identified to be associated with higher BMI among asthmatics (interaction p < 5×10-7 in MESA and p < 0.05 in FHS). In both MESA and FHS asthmatics, subjects carrying the A allele on rs2107212 had significantly higher odds of obesity than non-carriers, which was not the case for non-asthmatics.We further examined BMI change subsequent to asthma diagnosis over a period of 26 years in FHS and demonstrated greater BMI increase among asthmatics compared to non-asthmatics. Asthmatics carrying the A allele at rs2107212 had significantly greater net BMI increase over the 26-year period compared to non-asthmatics. In this study, we found that common genetic variants on 17q21.2 are associated with postasthma BMI increase among Caucasians. This finding will help elucidate pathways involved in the comorbidity of asthma and obesity.
UR - http://www.scopus.com/inward/record.url?scp=84956643396&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0144114
DO - 10.1371/journal.pone.0144114
M3 - Article
C2 - 26672748
AN - SCOPUS:84956643396
SN - 1932-6203
VL - 10
JO - PloS one
JF - PloS one
IS - 12
M1 - e0144114
ER -