The Human Obesity Gene Map: The 2005 Update

Rankinen, Tuomo; Zuberi, Aamir; Chagnon, Yvon C.; Weisnagel, S. John; Argyropoulos, George; Walts, Brandon; Pérusse, Louis; Bouchard, Claude

doi:10.1038/oby.2006.71

Cited by 965 publications

(827 citation statements)

References 1,284 publications

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“…There are known Mendelian disorders resulting from single-gene mutations that cause severe obesity, which usually starts already in childhood. 11,12 These studies are out of the scope of this review. We limited childhood period from 1 to 18 years.…”

Section: Search Strategymentioning

confidence: 99%

“…There are a lot of studies on the candidate genes of BMI, but only few of them include children. 11,12 It would thus be important to replicate the found candidate genes in children, which may also give more insight into the biological mechanisms behind these effects. Twin studies are useful in this area as they allow estimating the proportion of the variation explained by the candidate genes of the total genetic variation.…”

Section: Further Prospectsmentioning

confidence: 99%

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The genetic and environmental influences on childhood obesity: a systematic review of twin and adoption studies

et al. 2009

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In this systematic review, we aimed to collect together all previous twin and adoption studies on childhood and adolescent obesity up to the age of 18 years. Using several sources, we identified nine twin and five adoption studies; all of these studies had used relative weight as an indicator of obesity. Except the two twin studies from the Korean population, all studies represented Caucasian populations. In a meta-analysis of these twin studies, we found that genetic factors had a strong effect on the variation of body mass index (BMI) at all ages. The common environmental factors showed a substantial effect in mid-childhood, but this effect disappeared at adolescence. Adoption studies supported the role of family environment in childhood obesity as correlations were found between adoptees and adoptive parents; however, correlations were substantially stronger between parents and their biological offspring, further supporting the importance of genetic factors. In the future, more studies implementing genetic and environmental measures into twin models are needed as they allow estimation of the proportion of total genetic variation explained by candidate genes and analyses of gene-environment interactions. More studies of genetic architecture in non-Caucasian populations, of gene-environment interactions, and of body composition and body fat distribution are needed. IntroductionChildhood obesity is one of the major public health problems in the modern world. In the period [2003][2004][2005][2006], 32% of the US children were classified as obese or overweight, 1 and increasing trends in childhood obesity are seen all over the world. 2 These results are especially alarming as overweight children show a high risk of becoming obese adults. 3,4 Childhood is an important period of life for health interventions as health-related behaviors are just in formation, and it seems possible to intervene for preventing the development of obesity. 5 Thus, it is crucial to further understand the background mechanisms of childhood obesity to find even more effective measures to prevent it before it begins to produce more or less irreversible health damages.Both genetic and environmental factors will probably contribute to childhood obesity. 6 Family studies have shown that obesity runs in families, although more detailed twin, adoption and family studies have shown that genetic differences between individuals explain a major proportion of the within-population variation in body mass index (BMI, kg m À2 ) in adulthood. [7][8][9] It is probable that genetic factors have an important role in childhood obesity also, but their role may be different or they may result from other genes than those that operate in adulthood. 10 The environmental factors shared by family members, such as co-twins in twin studies, have shown only a slight effect on the variation of adult BMI. 7,8 However, they may have a more important role in childhood, where parents and their offspring live together and where siblings obviously have a much greater opportu...

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Section: Search Strategymentioning

confidence: 99%

Section: Further Prospectsmentioning

confidence: 99%

The genetic and environmental influences on childhood obesity: a systematic review of twin and adoption studies

et al. 2009

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“…7 Although environmental factors have an important function, there is significant evidence for a heritable component in obesity. 8,9 In general, the total variance in BMI explained by genetic factors varies between 20 and 90%, with a most probable value around 40%. 10,11 For waist, the heritability estimates range from 40 to 80%.…”

Section: Introductionmentioning

confidence: 99%

Genetic variations in regulatory pathways of fatty acid and glucose metabolism are associated with obesity phenotypes: a population-based cohort study

et al. 2009

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Background: As nuclear receptors and transcription factors have an important regulatory function in adipocyte differentiation and fat storage, genetic variation in these key regulators and downstream pathways may be involved in the onset of obesity. Objective: To explore associations between single nucleotide polymorphisms (SNPs) in candidate genes from regulatory pathways that control fatty acid and glucose metabolism, and repeated measurements of body mass index (BMI) and waist circumference in a large Dutch study population. Methods: Data of 327 SNPs across 239 genes were analyzed for 3575 participants of the Doetinchem cohort, who were examined three times during 11 years, using the Illumina Golden Gate assay. Adjusted random coefficient models were used to analyze the relationship between SNPS and obesity phenotypes. False discovery rate q-values were calculated to account for multiple testing. Significance of the associations was defined as a q-value p0.20. Results: Two SNPs (in NR1H4 and SMARCA2 in women only) were significantly associated with both BMI and waist circumference. In addition, two SNPs (in SIRT1 and SCAP in women only) were associated with BMI alone. A functional SNP, in IL6, was strongly associated with waist. Conclusion: In this explorative study among participants of a large population-based cohort, five SNPs, mainly located in transcription mediator genes, were strongly associated with obesity phenotypes. The results from whole genome and candidate gene studies support the potential role of NR1H4, SIRT1, SMARCA2 and IL6 in obesity. Although replication of our findings and further research on the functionality of these SNPs and underlying mechanism is necessary, our data indirectly suggest a role of GATA transcription factors in weight control.

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“…Little is known about the pathophysiological role of NR1H3 in humans. Although NR1H3 is not located in a susceptibility locus for the metabolic syndrome or related traits from genetic linkage analysis according to the 2005 Obesity Gene Map, 7 one study found significant association between a NR1H3 polymorphism and body mass index in Swedish women. 8 Therefore, we performed a large-scale association study of NR1H3 in two large French population-based studies (n ¼ 1130 and 1160).…”

Section: Introductionmentioning

confidence: 99%

Association between liver X receptor α gene polymorphisms and risk of metabolic syndrome in French populations

et al. 2008

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Context:The metabolic syndrome is a complex and multifactorial disorder often associated with type 2 diabetes mellitus and cardiovascular diseases. The liver X receptor a (NR1H3) plays numerous roles in metabolic pathways involved in metabolic syndrome. Objective: In the search for susceptibility genes to metabolic syndrome, we hypothesized that common genetic variation in NR1H3 gene influences metabolic syndrome susceptibility. Design: Two large French population-based studies (n ¼ 1130 and 1160) including overall 664 individuals with and 1626 individuals without metabolic syndrome were genotyped for three polymorphisms (rs12221497, rs11039155 and rs2279239) of NR1H3. Results: We found that the À6A allele of rs11039155 was consistently associated with a 30% reduction in risk of metabolic syndrome in the two independent population samples (adjusted OR (95% CI) ¼ 0.68 (0.53-0.86), P ¼ 0.001 for the combined sample). Moreover, it was associated with an increase in plasma HDL-cholesterol concentrations (P ¼ 0.02 for the combined sample). Neither rs12221497 nor rs11039155, both polymorphisms located in the 5 0 region of NR1H3, had significant influence on NR1H3 and ATP-binding cassette transporter A1 (ABCA1) gene expression in primary human macrophages. Conclusions: These results suggest that NR1H3 plays an important role in the HDL-cholesterol metabolism and in the genetic susceptibility to metabolic syndrome.

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The Human Obesity Gene Map: The 2005 Update

Abstract: RANKINEN, TUOMO, AAMIR

Cited by 965 publications

References 1,284 publications

The genetic and environmental influences on childhood obesity: a systematic review of twin and adoption studies

The genetic and environmental influences on childhood obesity: a systematic review of twin and adoption studies

Genetic variations in regulatory pathways of fatty acid and glucose metabolism are associated with obesity phenotypes: a population-based cohort study

Association between liver X receptor α gene polymorphisms and risk of metabolic syndrome in French populations

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