BMI loci and longitudinal BMI from adolescence to young adulthood in an ethnically diverse cohort

Mariaelisa Graff, Kari E North, A. S. Richardson, K. L. Young, A. L. Mazul, H. M. Highland, K. L. Mohlke, Leslie A Lange, E. M. Lange, K. Mullan Harris, P. Gordon-Larsen

Research output: Contribution to journalArticle

  • 3 Citations

Abstract

Objective:The association of obesity susceptibility variants with change in body mass index (BMI) across the life course is not well understood.Subjects:In ancestry-stratified models of 5962 European American (EA), 2080 African American (AA) and 1582 Hispanic American (HA) individuals from the National Longitudinal Study of Adolescent to Adult Health (Add Health), we examined associations between 34 obesity single-nucleotide polymorphisms (SNPs) with per year change in BMI, measured by the slope from a growth-curve analysis of two or more BMI measurements between adolescence and young adulthood. For SNPs nominally associated with BMI change (P<0.05), we interrogated age differences within data collection Wave and time differences between age categories that overlapped between Waves.Results:We found SNPs in/near FTO, MC4R, MTCH2, TFAP2B, SEC16B and TMEM18 were significantly associated (P<0.0015≈0.05/34) with BMI change in EA and the ancestry-combined meta-analysis. rs9939609 in FTO met genome-wide significance at P<5e-08 in the EA and ancestry-combined analysis, respectively [Beta(se)=0.025(0.004);Beta(se)=0.021(0.003)]. No SNPs were significant after Bonferroni correction in AA or HA, although five SNPs in AA and four SNPs in HA were nominally significant (P<0.05). In EA and the ancestry-combined meta-analysis, rs3817334 near MTCH2 showed larger effects in younger respondents, whereas rs987237 near TFAP2B, showed larger effects in older respondents across all Waves. Differences in effect estimates across time for MTCH2 and TFAP2B are suggestive of either era or cohort effects.Conclusion:The observed association between variants in/near FTO, MC4R, MTCH2, TFAP2B, SEC16B and TMEM18 with change in BMI from adolescence to young adulthood suggest that the genetic effect of BMI loci varies over time in a complex manner, highlighting the importance of investigating loci influencing obesity risk across the life course.

LanguageEnglish (US)
Pages759-768
Number of pages10
JournalInternational Journal of Obesity
Volume41
Issue number5
DOIs
StatePublished - May 1 2017

Fingerprint

Body Mass Index
Single Nucleotide Polymorphism
Hispanic Americans
African Americans
Obesity
Meta-Analysis
Cohort Effect
Longitudinal Studies
Genome
Health
Growth
Surveys and Questionnaires

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

BMI loci and longitudinal BMI from adolescence to young adulthood in an ethnically diverse cohort. / Graff, Mariaelisa; North, Kari E; Richardson, A. S.; Young, K. L.; Mazul, A. L.; Highland, H. M.; Mohlke, K. L.; Lange, Leslie A; Lange, E. M.; Mullan Harris, K.; Gordon-Larsen, P.

In: International Journal of Obesity, Vol. 41, No. 5, 01.05.2017, p. 759-768.

Research output: Contribution to journalArticle

Graff, M, North, KE, Richardson, AS, Young, KL, Mazul, AL, Highland, HM, Mohlke, KL, Lange, LA, Lange, EM, Mullan Harris, K & Gordon-Larsen, P 2017, 'BMI loci and longitudinal BMI from adolescence to young adulthood in an ethnically diverse cohort' International Journal of Obesity, vol. 41, no. 5, pp. 759-768. https://doi.org/10.1038/ijo.2016.233
Graff, Mariaelisa ; North, Kari E ; Richardson, A. S. ; Young, K. L. ; Mazul, A. L. ; Highland, H. M. ; Mohlke, K. L. ; Lange, Leslie A ; Lange, E. M. ; Mullan Harris, K. ; Gordon-Larsen, P. / BMI loci and longitudinal BMI from adolescence to young adulthood in an ethnically diverse cohort. In: International Journal of Obesity. 2017 ; Vol. 41, No. 5. pp. 759-768.
@article{ba4107dcb428477a9a495a86dfb4eda7,
title = "BMI loci and longitudinal BMI from adolescence to young adulthood in an ethnically diverse cohort",
abstract = "Objective:The association of obesity susceptibility variants with change in body mass index (BMI) across the life course is not well understood.Subjects:In ancestry-stratified models of 5962 European American (EA), 2080 African American (AA) and 1582 Hispanic American (HA) individuals from the National Longitudinal Study of Adolescent to Adult Health (Add Health), we examined associations between 34 obesity single-nucleotide polymorphisms (SNPs) with per year change in BMI, measured by the slope from a growth-curve analysis of two or more BMI measurements between adolescence and young adulthood. For SNPs nominally associated with BMI change (P<0.05), we interrogated age differences within data collection Wave and time differences between age categories that overlapped between Waves.Results:We found SNPs in/near FTO, MC4R, MTCH2, TFAP2B, SEC16B and TMEM18 were significantly associated (P<0.0015≈0.05/34) with BMI change in EA and the ancestry-combined meta-analysis. rs9939609 in FTO met genome-wide significance at P<5e-08 in the EA and ancestry-combined analysis, respectively [Beta(se)=0.025(0.004);Beta(se)=0.021(0.003)]. No SNPs were significant after Bonferroni correction in AA or HA, although five SNPs in AA and four SNPs in HA were nominally significant (P<0.05). In EA and the ancestry-combined meta-analysis, rs3817334 near MTCH2 showed larger effects in younger respondents, whereas rs987237 near TFAP2B, showed larger effects in older respondents across all Waves. Differences in effect estimates across time for MTCH2 and TFAP2B are suggestive of either era or cohort effects.Conclusion:The observed association between variants in/near FTO, MC4R, MTCH2, TFAP2B, SEC16B and TMEM18 with change in BMI from adolescence to young adulthood suggest that the genetic effect of BMI loci varies over time in a complex manner, highlighting the importance of investigating loci influencing obesity risk across the life course.",
author = "Mariaelisa Graff and North, {Kari E} and Richardson, {A. S.} and Young, {K. L.} and Mazul, {A. L.} and Highland, {H. M.} and Mohlke, {K. L.} and Lange, {Leslie A} and Lange, {E. M.} and {Mullan Harris}, K. and P. Gordon-Larsen",
year = "2017",
month = "5",
day = "1",
doi = "10.1038/ijo.2016.233",
language = "English (US)",
volume = "41",
pages = "759--768",
journal = "International Journal of Obesity",
issn = "0307-0565",
publisher = "Nature Publishing Group",
number = "5",

}

TY - JOUR

T1 - BMI loci and longitudinal BMI from adolescence to young adulthood in an ethnically diverse cohort

AU - Graff, Mariaelisa

AU - North, Kari E

AU - Richardson, A. S.

AU - Young, K. L.

AU - Mazul, A. L.

AU - Highland, H. M.

AU - Mohlke, K. L.

AU - Lange, Leslie A

AU - Lange, E. M.

AU - Mullan Harris, K.

AU - Gordon-Larsen, P.

PY - 2017/5/1

Y1 - 2017/5/1

N2 - Objective:The association of obesity susceptibility variants with change in body mass index (BMI) across the life course is not well understood.Subjects:In ancestry-stratified models of 5962 European American (EA), 2080 African American (AA) and 1582 Hispanic American (HA) individuals from the National Longitudinal Study of Adolescent to Adult Health (Add Health), we examined associations between 34 obesity single-nucleotide polymorphisms (SNPs) with per year change in BMI, measured by the slope from a growth-curve analysis of two or more BMI measurements between adolescence and young adulthood. For SNPs nominally associated with BMI change (P<0.05), we interrogated age differences within data collection Wave and time differences between age categories that overlapped between Waves.Results:We found SNPs in/near FTO, MC4R, MTCH2, TFAP2B, SEC16B and TMEM18 were significantly associated (P<0.0015≈0.05/34) with BMI change in EA and the ancestry-combined meta-analysis. rs9939609 in FTO met genome-wide significance at P<5e-08 in the EA and ancestry-combined analysis, respectively [Beta(se)=0.025(0.004);Beta(se)=0.021(0.003)]. No SNPs were significant after Bonferroni correction in AA or HA, although five SNPs in AA and four SNPs in HA were nominally significant (P<0.05). In EA and the ancestry-combined meta-analysis, rs3817334 near MTCH2 showed larger effects in younger respondents, whereas rs987237 near TFAP2B, showed larger effects in older respondents across all Waves. Differences in effect estimates across time for MTCH2 and TFAP2B are suggestive of either era or cohort effects.Conclusion:The observed association between variants in/near FTO, MC4R, MTCH2, TFAP2B, SEC16B and TMEM18 with change in BMI from adolescence to young adulthood suggest that the genetic effect of BMI loci varies over time in a complex manner, highlighting the importance of investigating loci influencing obesity risk across the life course.

AB - Objective:The association of obesity susceptibility variants with change in body mass index (BMI) across the life course is not well understood.Subjects:In ancestry-stratified models of 5962 European American (EA), 2080 African American (AA) and 1582 Hispanic American (HA) individuals from the National Longitudinal Study of Adolescent to Adult Health (Add Health), we examined associations between 34 obesity single-nucleotide polymorphisms (SNPs) with per year change in BMI, measured by the slope from a growth-curve analysis of two or more BMI measurements between adolescence and young adulthood. For SNPs nominally associated with BMI change (P<0.05), we interrogated age differences within data collection Wave and time differences between age categories that overlapped between Waves.Results:We found SNPs in/near FTO, MC4R, MTCH2, TFAP2B, SEC16B and TMEM18 were significantly associated (P<0.0015≈0.05/34) with BMI change in EA and the ancestry-combined meta-analysis. rs9939609 in FTO met genome-wide significance at P<5e-08 in the EA and ancestry-combined analysis, respectively [Beta(se)=0.025(0.004);Beta(se)=0.021(0.003)]. No SNPs were significant after Bonferroni correction in AA or HA, although five SNPs in AA and four SNPs in HA were nominally significant (P<0.05). In EA and the ancestry-combined meta-analysis, rs3817334 near MTCH2 showed larger effects in younger respondents, whereas rs987237 near TFAP2B, showed larger effects in older respondents across all Waves. Differences in effect estimates across time for MTCH2 and TFAP2B are suggestive of either era or cohort effects.Conclusion:The observed association between variants in/near FTO, MC4R, MTCH2, TFAP2B, SEC16B and TMEM18 with change in BMI from adolescence to young adulthood suggest that the genetic effect of BMI loci varies over time in a complex manner, highlighting the importance of investigating loci influencing obesity risk across the life course.

UR - http://www.scopus.com/inward/record.url?scp=85009801522&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85009801522&partnerID=8YFLogxK

U2 - 10.1038/ijo.2016.233

DO - 10.1038/ijo.2016.233

M3 - Article

VL - 41

SP - 759

EP - 768

JO - International Journal of Obesity

T2 - International Journal of Obesity

JF - International Journal of Obesity

SN - 0307-0565

IS - 5

ER -