Genome-wide association to body mass index and waist circumference: the Framingham Heart Study 100K project

Genome-wide association to body mass index and waist circumference: the Framingham Heart Study 100K project
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DOI:
10.1186/1471-2350-8-s1-s18
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发表时间:
2007-01-01
影响因子:
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通讯作者:
Atwood, Larry D.
Atwood, Larry D.
中科院分区:
医学4区
文献类型:
--
作者:
Fox, Caroline S.;Heard-Costa, Nancy;Atwood, Larry D.

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背景:肥胖与多种心血管疾病(CVD)危险因素以及CVD相关,并且具有很强的家族性。我们测试的关联的单核苷酸多态性的Affyestival 100 K SNP基因芯片和肥胖的措施在心脏研究的心脏研究。方法:共有1341心脏研究参与者在310个家庭的Affyestival 100 K SNP基因芯片基因分型的肥胖特征测量超过30年的后续行动。在多个检查周期测量体重指数(BMI)、腰围(WC)、体重变化、身高和肥胖的放射学指标(皮下脂肪组织、内脏脂肪组织、腰围、矢状高度)。多变量调整残差,调整年龄,年龄平方,性别,吸烟,绝经状态,与基因型数据使用加性广义估计方程(GEE)和家庭为基础的关联检验(FBAT)模型进行了评估。我们将平均BMI优先于后代检查(1-7)和队列检查(10,16,18,20,22,24,26),平均WC优先于后代检查(4-7)。我们评估了常染色体上70,987个SNP的相关性,次要等位基因频率至少为0.10,Hardy-Weinberg平衡p >= 0.001,调用率至少为80%。通过GEE与平均BMI和平均WC相关的最高SNP是rs 110683(p值1.22* 10(-7))和rs 4471028(p值1.96* 10(-7))。请访问http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi? id= phs 000007以获得完整的结果集。我们能够验证已知基因中与BMI或其他肥胖性状相关的SNP,包括ESR 1 Xba 1 SNP、PPARG和ADIPOQ.Conclusion:肥胖性状与Affytek 100 K SNP基因芯片上的SNP相关。有必要复制这些初步调查结果。这些数据将作为复制的资源,因为更多的基因被确定与BMI和WC。
Background: Obesity is related to multiple cardiovascular disease ( CVD) risk factors as well as CVD and has a strong familial component. We tested for association between SNPs on the Affymetrix 100K SNP GeneChip and measures of adiposity in the Framingham Heart Study.Methods: A total of 1341 Framingham Heart Study participants in 310 families genotyped with the Affymetrix 100K SNP GeneChip had adiposity traits measured over 30 years of follow up. Body mass index ( BMI), waist circumference ( WC), weight change, height, and radiographic measures of adiposity ( subcutaneous adipose tissue, visceral adipose tissue, waist circumference, sagittal height) were measured at multiple examination cycles. Multivariable-adjusted residuals, adjusting for age, age-squared, sex, smoking, and menopausal status, were evaluated in association with the genotype data using additive Generalized Estimating Equations ( GEE) and Family Based Association Test ( FBAT) models. We prioritized mean BMI over offspring examinations ( 1-7) and cohort examinations ( 10, 16, 18, 20, 22, 24, 26) and mean WC over offspring examinations ( 4-7) for presentation. We evaluated associations with 70,987 SNPs on autosomes with minor allele frequencies of at least 0.10, Hardy-Weinberg equilibrium p >= 0.001, and call rates of at least 80%.Results: The top SNPs to be associated with mean BMI and mean WC by GEE were rs110683 ( p-value 1.22* 10(-7)) and rs4471028 ( p-values 1.96* 10(-7)). Please see http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007 for the complete set of results. We were able to validate SNPs in known genes that have been related to BMI or other adiposity traits, including the ESR1 Xba1 SNP, PPARG, and ADIPOQ.Conclusion: Adiposity traits are associated with SNPs on the Affymetrix 100K SNP GeneChip. Replication of these initial findings is necessary. These data will serve as a resource for replication as more genes become identified with BMI and WC.