The Human Obesity Gene Map: The 2004 Update

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

doi:10.1038/oby.2005.50

Cited by 265 publications

(186 citation statements)

References 1,057 publications

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“…1 Although several obesity quantitative trait loci (QTLs) have been mapped by linkage analysis, identification of underlying susceptibility genes shows slow progress. 2 Recently, genome-wide association studies have identified INSIG2 and FTO as primary obesity genes. 3,4 The association with INSIG2 has not been confirmed in all subsequent studies.…”

Section: Introductionmentioning

confidence: 99%

Association analysis of positional obesity candidate genes based on integrated data from transcriptomics and linkage analysis

et al. 2008

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Context: Obesity is a typical complex disorder resulting from behaviors promoted in westernized societies in the presence of a genetic predisposition. We hypothesized that new genes predisposing to obesity can be detected at the mRNA level. Objective: To identify susceptibility genes for obesity. Design: Linkage and expression profile data from different cohorts were combined to select novel candidate genes that were analyzed for association with obesity. Setting and participants: University Hospital in Stockholm. Adipose tissue mRNA levels were quantified in 96 women. Two large cohorts with a wide distribution in body mass index (BMI, n ¼ 1013 and 1423) were genotyped. Main outcome measure: mRNA levels and allelic association with obesity. Results: We confirmed association between candidate gene mRNA levels in adipose tissue and obesity. A total of 118 polymorphisms in 16 genes were analyzed for association with obesity. Single nucleotide polymorphism rs1064891, located in the 3 0 UTR of the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) gene, was nominally associated with obesity in combined analysis of cohorts 1 and 2 (P ¼ 0.007) and, in men that were lean or had severe obesity, with BMI (P ¼ o0.005). Conclusion: To combine linkage and expression profile data is valuable in finding new obesity genes. PFKFB3, a potential regulator of glycolysis, displays decreased mRNA levels in adipose tissue of obese women, is associated with obesity and is a new promising candidate gene for obesity warranting further studies.

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Section: Introductionmentioning

confidence: 99%

Association analysis of positional obesity candidate genes based on integrated data from transcriptomics and linkage analysis

et al. 2008

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“…4,5 Numerous molecular studies have been launched to search for genetic determinants underlying the variations of obesity-related phenotypes, involving more than 600 genes, markers and chromosomal regions. 6 The CYP19A1 gene encodes the aromatase, an enzyme that catalyses the conversions of C19 androgens, androstenedione and testosterone, to C18 estrogens, estrone and estradiol, respectively. [7][8][9] Testosterone inhibits preadipocyte proliferation and differentiation, 10,11 whereas estradiol appears to stimulate them.…”

Section: Introductionmentioning

confidence: 99%

CYP19A1 genetic polymorphisms may be associated with obesity-related phenotypes in Chinese women

et al. 2006

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The CYP19A1 protein (aromatase) plays a critical role in estrogen biosynthesis and thus affects body fat distribution and regulation. Object: To examine the relationship between genetic polymorphisms of the CYP19A1 gene and obesity-related phenotypes, body mass index (BMI) and waist-to-hip ratio (WHR). Subjects: In total, 1241 Chinese women, who were recruited as community controls for a population-based case-control study of breast cancer. Methods: Nineteen haplotype tagging single nucleotide polymorphisms (htSNPs) in four haplotype blocks were genotyped. Results: Significant associations were observed for WHR at three SNPs that are located in haplotype block 1, including rs2445765, rs1004984 and rs1902584 (P ¼ 0.05, 0.04 and 0.01, respectively). Women, particularly premenopausal women, who carried the minor allele at any of these SNPs, had higher WHR than those without it. Of these three SNPs, the strongest association was observed at rs1902584, which is the closest to Promoter I.4, the major promoter for adipose tissue. Haplotype analyses indicated an association between the haplotype TCCAT in block 1 and WHR with a P-value of 0.02. Conclusion: These results suggested that CYP19A1 genetic polymorphisms may be associated with the risk of obesity among Chinese women, especially among premenopausal women.

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“…[2][3][4] The gene encoding ERRa (ESRRA) is located on chromosome 11q13, a chromosomal region that has shown genetic linkage to body mass index (BMI) and fat percentage. 5,6 A pseudo gene has been identified on chromosome 13q12.1. 7 ESRRA is expressed in several tissues, but most abundantly in tissues with a high capacity for b-oxidation, such as skeletal muscle, heart, kidney, liver and adipose tissue.…”

Section: Introductionmentioning

confidence: 99%

Genetic analysis of the estrogen-related receptor α and studies of association with obesity and type 2 diabetes

et al. 2006

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Background: The estrogen-related receptor a (ERRa or NR3B1) is a transcription factor from the nuclear receptor super-family, group III. The gene encoding ERRa (ESRRA) is located on chromosome 11q13, a region showing genetic linkage to body mass index and fat percentage. Through interaction with the peroxisome proliferator-activated receptor-g coactivator-1a (PGC-1a), ERRa regulates key enzymes involved in the b-oxidation of fatty acids. Results: By screening 48 overweight or obese subjects for variants in the exons, exon-intron boundaries and 1000 base pairs (bp) of the promoter region of ESRRA using bi-directional nucleotide sequencing, we identified seven variants. Four rare variants had minor allele frequencies (MAF) below 1%: Pro369Pro, Gly406Asp, 3 0 UTR þ 418G4A, 3 0 UTR þ 505C4A. Two singlenucleotide polymorphisms, Pro116Pro and IVS6 þ 65C4T (MAF 15%), were in complete linkage disequilibrium (LD) (r 2 ¼ 1). We also confirmed the presence of a reported 23 bp microsatellite repeat (ESRRA23). The Pro116Pro and ESRRA23 variants were not associated with obesity, type 2 diabetes or related phenotypes in a large population-based study of 6365 Danish whites. The two variants were examined for interactions with variants in the peroxisome proliferator-activated receptor-g coactivator-1a and -b; however, no evidence of epistatic effects between the variants was demonstrated. Conclusion: The ESRRA23 and Pro116Pro variants of the gene encoding ERRa are not associated with obesity, type 2 diabetes or related quantitative traits in the examined Danish whites.

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The Human Obesity Gene Map: The 2004 Update

Abstract: PÉ RUSSE, LOUIS, TUOMO RANKINEN, AAMIR

Cited by 265 publications

References 1,057 publications

Association analysis of positional obesity candidate genes based on integrated data from transcriptomics and linkage analysis

Association analysis of positional obesity candidate genes based on integrated data from transcriptomics and linkage analysis

CYP19A1 genetic polymorphisms may be associated with obesity-related phenotypes in Chinese women

Genetic analysis of the estrogen-related receptor α and studies of association with obesity and type 2 diabetes

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