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美国印第安人 BMI 的全基因组关联研究。

A genome-wide association study of BMI in American Indians.

机构信息

Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona, USA.

出版信息

Obesity (Silver Spring). 2011 Oct;19(10):2102-6. doi: 10.1038/oby.2011.178. Epub 2011 Jun 23.

Abstract

Numerous studies have been done to understand genetic contributors to BMI, but only a limited number of studies have been done in nonwhite groups such as American Indians. A genome-wide association study (GWAS) for BMI was therefore performed in Pima Indians. BMI measurements from a longitudinal study of 1,120 Pima Indians and 454,194 single-nucleotide polymorphisms (SNPs) from the 1 million Affymetrix SNP panel were used (35% of SNPs were excluded due to minor allele frequency <0.05). Data included BMI measured at multiple examinations collected from 1965 to 2004, as well as the maximum BMI at one of these visits. General and within-family tests were performed using a maximum-likelihood based mixed model procedure. No SNP reached a genome-wide significance level (estimated at P < 4.94 × 10(-7)). For repeated measures analyses, the strongest associations for general and within-family tests mapped to two different regions on chromosome 6 (rs9342220 (P = 1.39 × 10(-6)) and rs7758764 (P = 2.51 × 10(-6)), respectively). For maximum BMI, the strongest association for the general tests mapped to chromosome 4 (rs17612333; P = 1.98 × 10(-6)) and to chromosome 3 (rs11127958; P = 1.53 × 10(-6)) for the within-family tests. Further analysis is important because only a few of these regions have been previously implicated in a GWAS and genetic susceptibility may differ by ethnicity.

摘要

已经进行了许多研究来了解 BMI 的遗传贡献,但仅在非白人群体(如美洲印第安人)中进行了有限数量的研究。因此,对皮马印第安人进行了 BMI 的全基因组关联研究(GWAS)。该研究使用了来自皮马印第安人纵向研究的 1120 名皮马印第安人和 454194 个单核苷酸多态性(SNP)的 BMI 测量值(由于次要等位基因频率<0.05,因此排除了 35%的 SNP)。数据包括从 1965 年至 2004 年期间多次检查中测量的 BMI,以及这些访问中的一次最大 BMI。使用基于最大似然的混合模型程序进行了一般和家庭内测试。没有 SNP 达到全基因组显着水平(估计为 P <4.94×10(-7))。对于重复测量分析,一般和家庭内测试的最强关联映射到染色体 6 上的两个不同区域(rs9342220(P = 1.39×10(-6))和 rs7758764(P = 2.51×10(-6)))。对于最大 BMI,一般测试的最强关联映射到染色体 4(rs17612333;P = 1.98×10(-6))和染色体 3(rs11127958;P = 1.53×10(-6))对于家庭内测试。进一步的分析很重要,因为以前仅在少数这些区域中发现了 GWAS ,并且遗传易感性可能因种族而异。

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