Influence of common variants near INSIG2, in FTO, and near MC4R genes on overweight and the metabolic profile in adolescence: the TRAILS (TRacking Adolescents' Individual Lives Survey) Study.
BACKGROUND
Overweight is a complex trait in which both environmental and genetic factors play a role.


OBJECTIVE
We aimed to evaluate the influence of common genetic variants identified by genome-wide association studies on overweight and the metabolic profile in adolescence.


METHODS
In a population-based cohort of 663 girls and 612 boys aged 16 y, weight, height, skinfold thicknesses, percentage body fat, waist circumference, blood pressure, glucose, insulin, lipid profile, and DNA were obtained. We defined overweight according to international criteria. We performed multiple linear and logistic regression analyses to assess the influence of candidate single nucleotide polymorphisms near the INSIG2, in the FTO, and near the MC4R genes and repeated-measures analyses of available body mass index (BMI) and skinfold thickness data across 3 visits at ages 11, 13.5, and 16 y.


RESULTS
A total of 15.1% of participants were overweight or obese at age 16 y. No associations with INSIG2 were found. Common variation in the FTO gene was associated with sex-specific z scores of BMI (B: 0.11; 95% CI: 0.03, 0.19), sum of skinfold thicknesses (B: 0.12; 95% CI: 0.04, 0.20), percentage body fat (B: 0.11; 95% CI: 0.03, 0.19), waist circumference (B: 0.11; 95% CI: 0.03, 0.19), fasting glucose (B: 0.10; 95% CI: 0.00, 0.20), and overweight (odds ratio: 1.34; 95% CI: 1.06, 1.69) at age 16 y. Repeated-measures analyses confirmed the associations for BMI and sum of skinfold thicknesses, and physical activity did not modify these associations. Common variation near the MC4R gene was associated with BMI in cross-sectional (B: 0.11; 95% CI: 0.02, 0.20) and repeated-measures (B: 0.12; 95% CI: 0.03, 0.20) analyses.


CONCLUSIONS
Common variation in the FTO gene is associated with overall and abdominal adiposity. Variation near the MC4R gene is associated with BMI. These findings in adolescents strengthen and extend the results from previous research.
Liem
Eryn T
ET
Department of Pediatrics-Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, Netherlands. e.t.liem@bkk.umcg.nl
Vonk
Judith M
JM
Sauer
Pieter J J
PJ
van der Steege
Gerrit
G
Oosterom
Elvira
E
Stolk
Ronald P
RP
Snieder
Harold
H
D000293:Adolescent; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000502:physiology; D001823:Body Composition / Q000502:physiology; D015992:Body Mass Index; D015331:Cohort Studies; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000097:blood; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008055:Lipids / Q000097:blood; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D050177:Overweight / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011506:Proteins / Q000235:genetics*; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics*; D055105:Waist Circumference / Q000502:physiology
D001786:Blood Glucose; C467727:INSIG2 protein, human; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D008055:Lipids; C470072:MC4R protein, human; D008565:Membrane Proteins; D011506:Proteins; D044105:Receptor, Melanocortin, Type 4; D004247:DNA; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human