A novel locus for body mass index on 5p15.2: A meta-analysis of two genome-wide association studies

Wang, Ke Sheng; Li, Xuefeng; Zheng, Shimin; Zeng, Min; Pan, Yue; Callahan, Katie

doi:10.1016/j.gene.2012.03.046

Cited by 12 publications

(10 citation statements)

References 30 publications

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“…It is compelling that our investigations show that many of the loci previously indicated as being associated with BMI [15], [17]–[20], [41], [42] contain no SNVs that are strongly associated with BMI in our sample. While the participants of these studies were primarily of recent European descent, one study in an African American population [21] and one in a Japanese population [22] found an association signal from a variant in the vicinity of FTO, which replicated a signal seen in populations of European ancestry [15], [18], [19], [41], [42].…”

Section: Discussionsupporting

confidence: 51%

Genome-Wide Association Studies and Heritability Estimates of Body Mass Index Related Phenotypes in Bangladeshi Adults

et al. 2014

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Many health outcomes are influenced by a person's body mass index, as well as by the trajectory of body mass index through a lifetime. Although previous research has established that body mass index related traits are influenced by genetics, the relationship between these traits and genetics has not been well characterized in people of South Asian ancestry. To begin to characterize this relationship, we analyzed the association between common genetic variation and five phenotypes related to body mass index in a population-based sample of 5,354 Bangladeshi adults. We discovered a significant association between SNV rs347313 (intron of NOS1AP) and change in body mass index in women over two years. In a linear mixed-model, the G allele was associated with an increase of 0.25 kg/m2 in body mass index over two years (p-value of 2.3·10−8). We also estimated the heritability of these phenotypes from our genotype data. We found significant estimates of heritability for all of the body mass index-related phenotypes. Our study evaluated the genetic determinants of body mass index related phenotypes for the first time in South Asians. The results suggest that these phenotypes are heritable and some of this heritability is driven by variation that differs from those previously reported. We also provide evidence that the genetic etiology of body mass index related traits may differ by ancestry, sex, and environment, and consequently that these factors should be considered when assessing the genetic determinants of the risk of body mass index-related disease.

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Section: Discussionsupporting

confidence: 51%

Genome-Wide Association Studies and Heritability Estimates of Body Mass Index Related Phenotypes in Bangladeshi Adults

et al. 2014

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“…The effect allele frequencies of the eight SNPs in the present study were similar to those reported in HapMap Han Chinese, however, different from the frequencies of the original findings in other populations (see Table 2). The effect allele frequency of rs2967951 varied at most, which was 0.67 in our study and 0.10 in Wang's study among Caucasians (8). The SNP rs6794092 was monomorphic in our study, but its effect allele frequency was 0.90 in Ng's study among African American (7).…”

Section: Association Of Eight Variants With Obesitycontrasting

confidence: 46%

“…Firstly, we selected six SNPs associated with BMI or obesity from two new GWAS in 2012 (7,8). Secondly, the SNP rs62048402 in FTO recently identified by Sällman et al (9) was included in the present study.…”

Section: Snps Selection and Genotypingmentioning

confidence: 99%

“…Firstly, in 2012, Ng et al (7) performed a meta-analysis of two GWAS and the replication in four cohorts of African Americans, revealing five SNPs at four loci (rs6794092 near transmembrane protein 212 (TMEM212), rs268972 near cadherin 12 (CDH12), rs2033195, and rs815611 between microfibrillar-associated protein 3 (MFAP3) and UDP-N-acetyl-alpha-D-galactosamine: polypeptide N-acetylgalactosaminyltransferase 10 (GALNT10), and rs6088887 near Fer-1-like 4 (FER1L4)) associated with BMI (2.4 × 10 −6 < P < 2.5 × 10 −5 ). In the same year, Wang et al (8) identified a novel locus that influences BMI based on metaanalysis of GWAS data of two Caucasian samples. The strongest associated marker was SNP rs2967951 in rhophilin-associated tail protein 1-like (ROPN1L) located at 5p15.2.…”

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confidence: 99%

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Association study of childhood obesity with eight genetic variants recently identified by genome-wide association studies

Meng

Song

et al. 2014

Pediatr Res

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Background:Being overweight or obese is becoming increasingly common in low-and middle-income countries. The present study aimed to examine association of eight genetic variants with obesity and to estimate the cumulative effects of these variants in Chinese children. Methods:We conducted the case-control study in a total of 2,030 subjects. Genotyping of seven novel variants was performed with matrix-assisted laser desorption ionization time of flight mass spectrometry, while rs9939609 was genotyped with tetra-primer amplification refractory mutation system analysis. results: The association of two fat mass and obesityassociated gene (FTO) single-nucleotide polymorphisms (SNPs; rs9939609 and rs62048402) with body mass index (BMI) or obesity reached nominal significance at P < 0.05. We found a cumulative effect of five SNPs on the risk of overweight and obesity (odds ratio (OR) = 1.197, 95% confidence interval (CI) = 1.068-1.342, P = 0.002). Subjects carrying 9 or more effect alleles had a 127% increased risk of overweight and obesity (OR = 2.270, 95% CI = 1.403-3.671, P = 0.001) compared with subjects who carry 6 or fewer effect alleles. conclusion: We confirmed two FTO SNPs (rs62048402 and rs9939609) had nominal significant effects on BMI or obesity. We identified the cumulative effect of five SNPs on risk of overweight and obesity. The results provided evidence for identifying genetic factors related to childhood obesity.

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“…Recently, an independent study (n = 4,325 cases and controls) also showed significant association of 5p15.2-rs1092913 with breast cancer risk in estrogen receptor positive breast cancer of Korean ethnicity, suggesting the potential generalizability of this SNP-breast cancer association in the Korean population [46]. Furthermore, a meta-analysis of two GWASs also found multiple SNPs within the ROP1NL locus associated with the phenotype of BMI at 5p15.2, suggesting that this region is important for both breast cancer susceptibility and BMI [47].…”

Section: Discussionmentioning

confidence: 83%

Identification of a Breast Cancer Susceptibility Locus at 4q31.22 Using a Genome-Wide Association Study Paradigm

et al. 2013

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More than 40 single nucleotide polymorphisms (SNPs) for breast cancer susceptibility were identified by genome-wide association studies (GWASs). However, additional SNPs likely contribute to breast cancer susceptibility and overall genetic risk, prompting this investigation for additional variants. Six putative breast cancer susceptibility SNPs identified in a two-stage GWAS that we reported earlier were replicated in a follow-up stage 3 study using an independent set of breast cancer cases and controls from Canada, with an overall cumulative sample size of 7,219 subjects across all three stages. The study design also encompassed the 11 variants from GWASs previously reported by various consortia between the years 2007–2009 to (i) enable comparisons of effect sizes, and (ii) identify putative prognostic variants across studies. All SNP associations reported with breast cancer were also adjusted for body mass index (BMI). We report a strong association with 4q31.22-rs1429142 (combined per allele odds ratio and 95% confidence interval = 1.28 [1.17–1.41] and P combined = 1.5×10−7), when adjusted for BMI. Ten of the 11 breast cancer susceptibility loci reported by consortia also showed associations in our predominantly Caucasian study population, and the associations were independent of BMI; four FGFR2 SNPs and TNRC9-rs3803662 were among the most notable associations. Since the original report by Garcia-Closas et al. 2008, this is the second study to confirm the association of 8q24.21-rs13281615 with breast cancer outcomes.

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A novel locus for body mass index on 5p15.2: A meta-analysis of two genome-wide association studies

Cited by 12 publications

References 30 publications

Genome-Wide Association Studies and Heritability Estimates of Body Mass Index Related Phenotypes in Bangladeshi Adults

Genome-Wide Association Studies and Heritability Estimates of Body Mass Index Related Phenotypes in Bangladeshi Adults

Association study of childhood obesity with eight genetic variants recently identified by genome-wide association studies

Identification of a Breast Cancer Susceptibility Locus at 4q31.22 Using a Genome-Wide Association Study Paradigm

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