Genetic risk sum score comprised of common polygenic variation is associated with body mass index.

paper Cited Public

Authors: Peterson, Roseann E; Maes, Hermine H; Holmans, Peter; Sanders, Alan R; Levinson, Douglas F; Shi, Jianxin; Kendler, Kenneth S; Gejman, Pablo V; Webb, Bradley T
Year: 2011
Journal: Human genetics
PMID: 21104096
DOI: 10.1007/s00439-010-0917-1
PMCID: PMC3403709

#	Section	Preview
0	Introduction	Obesity is a general medical condition, defined clinically by a body mass index (BMI) greater than…
1	Introduction	Genome-wide association studies (GWAS) have successfully identified polymorphisms that contribute to…
2	Introduction	MC4R. These variants were highly significant but had modest effects with 0.06–0.4 kg/m2 per allele…
3	Introduction	Replication attempts using studies unselected for BMI have limited power to achieve genome-wide…
4	Introduction	predictive of type II diabetes, though algorithms including family history and additional risk…
5	Introduction	The purpose of this study was to test a GRSS comprising replicated genome-wide significant variants…
6	Materials and methods — Participants and phenotypes	The MGS-C sample has been previously described in detail (Sanders et al. 2008; Shi et al. 2009;…
7	Materials and methods — Genotyping	Venipuncture for DNA extraction and establishment of lymphoblastoid cell lines was completed at…
8	Materials and methods — Selection of 56 SNPs	Preliminary SNP selection identified 78 variants meeting criteria for genome-wide or suggestive…
9	Materials and methods — Selection of 56 SNPs	one SNP, rs10938397 on 4p12, could not be compared between meta-analyses because there was no…
10	Materials and methods — Selection of 56 SNPs	selection threshold was more liberal than the traditional genome-wide significance threshold, it was…
11	Materials and methods — Genetic risk sum score	Under an additive model, 56 variants were used to construct the GRSS. The use of an additive model…
12	Materials and methods — Prediction of obesity	One method to assess diagnostic efficiency is to graph a receiver operator criteria (ROC) curve,…
13	Results — Phenotypic detail	Descriptive statistics for age and BMI are presented by race and sex in Table 1. The mean age of…
14	Results — Phenotypic detail	expected, females had significantly greater BMI than males with African-American females having…
15	Results — Genetic risk sum score	Fifty-six variants catalogued from two large-scale BMI meta-analyses were used to construct the GRSS…
16	Results — Genetic risk sum score	Results from linear regression analyses are presented in Table 2. Standard covariates known to…
17	Results — Genetic risk sum score	to the base model, fits significantly better [F (1,3027) = 21.8, p = 3.2E−06] and accounted for an…
18	Results — Genetic risk sum score	The relative contributions of the individual loci to the GRSS were examined post hoc by dropping the…
19	Results — Prediction of obesity	To test the discriminative accuracy of the GRSS and covariates (molecularly derived ancestry, sex,…

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In this knowledge base

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Development and evaluation of a genetic risk score for obesity.	2013	23701538
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