Absence of association between the INSIG2 gene polymorphism (rs7566605) and obesity in the European Youth Heart Study (EYHS)

Karani S Vimaleswaran, Paul W Franks, Soren Brage, Luis B Sardinha, Lars B Andersen, Nicholas J Wareham, Ulf Ekelund, Ruth J F Loos

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

The first genome-wide association study for BMI identified a polymorphism, rs7566605, 10 kb upstream of the insulin-induced gene 2 (INSIG2) transcription start site, as the most significantly associated variant in children and adults. Subsequent studies, however, showed inconsistent association of this polymorphism with obesity traits. This polymorphism has been hypothesized to alter INSIG2 expression leading to inhibition of fatty acid and cholesterol synthesis. Hence, we investigated the association of the INSIG2 rs7566605 polymorphism with obesity- and lipid-related traits in Danish and Estonian children (930 boys and 1,073 girls) from the European Youth Heart Study (EYHS), a school-based, cross-sectional study of pre- and early pubertal children. The association between the polymorphism and obesity traits was tested using additive and recessive models adjusted for age, age-group, gender, maturity and country. Interactions were tested by including the interaction terms in the model. Despite having sufficient power (98%) to detect the previously reported effect size for association with BMI, we did not find significant effects of rs7566605 on BMI (additive, P = 0.68; recessive, P = 0.24). Accordingly, the polymorphism was not associated with overweight (P = 0.87) or obesity (P = 0.34). We also did not find association with waist circumference (WC), sum of four skinfolds, or with total cholesterol, triglycerides, low-density lipoprotein, or high-density lipoprotein. There were no gender-specific (P = 0.55), age-group-specific (P = 0.63) or country-specific (P = 0.56) effects. There was also no evidence of interaction between genotype and physical activity (P = 0.95). Despite an adequately powered study, our findings suggest that rs7566605 is not associated with obesity-related traits and lipids in the EYHS.
Original languageEnglish
JournalObesity
Volume17
Issue number7
Pages (from-to)1453-7
Number of pages4
ISSN1930-7381
DOIs
Publication statusPublished - 1. Jul 2009

Fingerprint

Insulin
Age Groups
Lipids
Genome-Wide Association Study
Transcription Initiation Site
HDL Lipoproteins
LDL Cholesterol
Fatty Acids
Cross-Sectional Studies
Exercise

Keywords

  • Adolescent
  • Child
  • Cross-Sectional Studies
  • Denmark
  • Estonia
  • Europe
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Lipids
  • Male
  • Membrane Proteins
  • Obesity
  • Polymorphism, Single Nucleotide
  • Waist Circumference

Cite this

Vimaleswaran, K. S., Franks, P. W., Brage, S., Sardinha, L. B., Andersen, L. B., Wareham, N. J., ... Loos, R. J. F. (2009). Absence of association between the INSIG2 gene polymorphism (rs7566605) and obesity in the European Youth Heart Study (EYHS). Obesity, 17(7), 1453-7. https://doi.org/10.1038/oby.2008.650
Vimaleswaran, Karani S ; Franks, Paul W ; Brage, Soren ; Sardinha, Luis B ; Andersen, Lars B ; Wareham, Nicholas J ; Ekelund, Ulf ; Loos, Ruth J F. / Absence of association between the INSIG2 gene polymorphism (rs7566605) and obesity in the European Youth Heart Study (EYHS). In: Obesity. 2009 ; Vol. 17, No. 7. pp. 1453-7.
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abstract = "The first genome-wide association study for BMI identified a polymorphism, rs7566605, 10 kb upstream of the insulin-induced gene 2 (INSIG2) transcription start site, as the most significantly associated variant in children and adults. Subsequent studies, however, showed inconsistent association of this polymorphism with obesity traits. This polymorphism has been hypothesized to alter INSIG2 expression leading to inhibition of fatty acid and cholesterol synthesis. Hence, we investigated the association of the INSIG2 rs7566605 polymorphism with obesity- and lipid-related traits in Danish and Estonian children (930 boys and 1,073 girls) from the European Youth Heart Study (EYHS), a school-based, cross-sectional study of pre- and early pubertal children. The association between the polymorphism and obesity traits was tested using additive and recessive models adjusted for age, age-group, gender, maturity and country. Interactions were tested by including the interaction terms in the model. Despite having sufficient power (98{\%}) to detect the previously reported effect size for association with BMI, we did not find significant effects of rs7566605 on BMI (additive, P = 0.68; recessive, P = 0.24). Accordingly, the polymorphism was not associated with overweight (P = 0.87) or obesity (P = 0.34). We also did not find association with waist circumference (WC), sum of four skinfolds, or with total cholesterol, triglycerides, low-density lipoprotein, or high-density lipoprotein. There were no gender-specific (P = 0.55), age-group-specific (P = 0.63) or country-specific (P = 0.56) effects. There was also no evidence of interaction between genotype and physical activity (P = 0.95). Despite an adequately powered study, our findings suggest that rs7566605 is not associated with obesity-related traits and lipids in the EYHS.",
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Vimaleswaran, KS, Franks, PW, Brage, S, Sardinha, LB, Andersen, LB, Wareham, NJ, Ekelund, U & Loos, RJF 2009, 'Absence of association between the INSIG2 gene polymorphism (rs7566605) and obesity in the European Youth Heart Study (EYHS)', Obesity, vol. 17, no. 7, pp. 1453-7. https://doi.org/10.1038/oby.2008.650

Absence of association between the INSIG2 gene polymorphism (rs7566605) and obesity in the European Youth Heart Study (EYHS). / Vimaleswaran, Karani S; Franks, Paul W; Brage, Soren; Sardinha, Luis B; Andersen, Lars B; Wareham, Nicholas J; Ekelund, Ulf; Loos, Ruth J F.

In: Obesity, Vol. 17, No. 7, 01.07.2009, p. 1453-7.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Absence of association between the INSIG2 gene polymorphism (rs7566605) and obesity in the European Youth Heart Study (EYHS)

AU - Vimaleswaran, Karani S

AU - Franks, Paul W

AU - Brage, Soren

AU - Sardinha, Luis B

AU - Andersen, Lars B

AU - Wareham, Nicholas J

AU - Ekelund, Ulf

AU - Loos, Ruth J F

PY - 2009/7/1

Y1 - 2009/7/1

N2 - The first genome-wide association study for BMI identified a polymorphism, rs7566605, 10 kb upstream of the insulin-induced gene 2 (INSIG2) transcription start site, as the most significantly associated variant in children and adults. Subsequent studies, however, showed inconsistent association of this polymorphism with obesity traits. This polymorphism has been hypothesized to alter INSIG2 expression leading to inhibition of fatty acid and cholesterol synthesis. Hence, we investigated the association of the INSIG2 rs7566605 polymorphism with obesity- and lipid-related traits in Danish and Estonian children (930 boys and 1,073 girls) from the European Youth Heart Study (EYHS), a school-based, cross-sectional study of pre- and early pubertal children. The association between the polymorphism and obesity traits was tested using additive and recessive models adjusted for age, age-group, gender, maturity and country. Interactions were tested by including the interaction terms in the model. Despite having sufficient power (98%) to detect the previously reported effect size for association with BMI, we did not find significant effects of rs7566605 on BMI (additive, P = 0.68; recessive, P = 0.24). Accordingly, the polymorphism was not associated with overweight (P = 0.87) or obesity (P = 0.34). We also did not find association with waist circumference (WC), sum of four skinfolds, or with total cholesterol, triglycerides, low-density lipoprotein, or high-density lipoprotein. There were no gender-specific (P = 0.55), age-group-specific (P = 0.63) or country-specific (P = 0.56) effects. There was also no evidence of interaction between genotype and physical activity (P = 0.95). Despite an adequately powered study, our findings suggest that rs7566605 is not associated with obesity-related traits and lipids in the EYHS.

AB - The first genome-wide association study for BMI identified a polymorphism, rs7566605, 10 kb upstream of the insulin-induced gene 2 (INSIG2) transcription start site, as the most significantly associated variant in children and adults. Subsequent studies, however, showed inconsistent association of this polymorphism with obesity traits. This polymorphism has been hypothesized to alter INSIG2 expression leading to inhibition of fatty acid and cholesterol synthesis. Hence, we investigated the association of the INSIG2 rs7566605 polymorphism with obesity- and lipid-related traits in Danish and Estonian children (930 boys and 1,073 girls) from the European Youth Heart Study (EYHS), a school-based, cross-sectional study of pre- and early pubertal children. The association between the polymorphism and obesity traits was tested using additive and recessive models adjusted for age, age-group, gender, maturity and country. Interactions were tested by including the interaction terms in the model. Despite having sufficient power (98%) to detect the previously reported effect size for association with BMI, we did not find significant effects of rs7566605 on BMI (additive, P = 0.68; recessive, P = 0.24). Accordingly, the polymorphism was not associated with overweight (P = 0.87) or obesity (P = 0.34). We also did not find association with waist circumference (WC), sum of four skinfolds, or with total cholesterol, triglycerides, low-density lipoprotein, or high-density lipoprotein. There were no gender-specific (P = 0.55), age-group-specific (P = 0.63) or country-specific (P = 0.56) effects. There was also no evidence of interaction between genotype and physical activity (P = 0.95). Despite an adequately powered study, our findings suggest that rs7566605 is not associated with obesity-related traits and lipids in the EYHS.

KW - Adolescent

KW - Child

KW - Cross-Sectional Studies

KW - Denmark

KW - Estonia

KW - Europe

KW - Female

KW - Genetic Predisposition to Disease

KW - Genotype

KW - Humans

KW - Intracellular Signaling Peptides and Proteins

KW - Lipids

KW - Male

KW - Membrane Proteins

KW - Obesity

KW - Polymorphism, Single Nucleotide

KW - Waist Circumference

U2 - 10.1038/oby.2008.650

DO - 10.1038/oby.2008.650

M3 - Journal article

C2 - 19197262

VL - 17

SP - 1453

EP - 1457

JO - Obesity

JF - Obesity

SN - 1930-7381

IS - 7

ER -