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- Aberg, KA, et al.
(författare)
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MBD-seq as a cost-effective approach for methylome-wide association studies: demonstration in 1500 case--control samples
- 2012
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Ingår i: Epigenomics. - : Future Medicine Ltd. - 1750-192X .- 1750-1911. ; 4:6, s. 605-621
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Tidskriftsartikel (refereegranskat)abstract
- Aim: We studied the use of methyl-CpG binding domain (MBD) protein-enriched genome sequencing (MBD-seq) as a cost-effective screening tool for methylome-wide association studies (MWAS). Materials & methods: Because MBD-seq has not yet been applied on a large scale, we first developed and tested a pipeline for data processing using 1500 schizophrenia cases and controls plus 75 technical replicates with an average of 68 million reads per sample. This involved the use of technical replicates to optimize quality control for multi- and duplicate-reads, an in silico experiment to identify CpGs in loci with alignment problems, CpG coverage calculations based on multiparametric estimates of the fragment size distribution, a two-stage adaptive algorithm to combine data from correlated adjacent CpG sites, principal component analyses to control for confounders and new software tailored to handle the large data set. Results: We replicated MWAS findings in independent samples using a different technology that provided single base resolution. In an MWAS of age-related methylation changes, one of our top findings was a previously reported robust association involving GRIA2. Our results also suggested that owing to the many confounding effects, a considerable challenge in MWAS is to identify those effects that are informative about disease processes. Conclusion: This study showed the potential of MBD-seq as a cost-effective tool in large-scale disease studies.
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- Benjamin, DJ, et al.
(författare)
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The genetic architecture of economic and political preferences
- 2012
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 109:21, s. 8026-8031
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Tidskriftsartikel (refereegranskat)abstract
- Preferences are fundamental building blocks in all models of economic and political behavior. We study a new sample of comprehensively genotyped subjects with data on economic and political preferences and educational attainment. We use dense single nucleotide polymorphism (SNP) data to estimate the proportion of variation in these traits explained by common SNPs and to conduct genome-wide association study (GWAS) and prediction analyses. The pattern of results is consistent with findings for other complex traits. First, the estimated fraction of phenotypic variation that could, in principle, be explained by dense SNP arrays is around one-half of the narrow heritability estimated using twin and family samples. The molecular-genetic–based heritability estimates, therefore, partially corroborate evidence of significant heritability from behavior genetic studies. Second, our analyses suggest that these traits have a polygenic architecture, with the heritable variation explained by many genes with small effects. Our results suggest that most published genetic association studies with economic and political traits are dramatically underpowered, which implies a high false discovery rate. These results convey a cautionary message for whether, how, and how soon molecular genetic data can contribute to, and potentially transform, research in social science. We propose some constructive responses to the inferential challenges posed by the small explanatory power of individual SNPs.
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- Benjamin, DJ, et al.
(författare)
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The Promises and Pitfalls of Genoeconomics*
- 2012
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Ingår i: Annual review of economics. - : Annual Reviews. - 1941-1383 .- 1941-1391. ; 4, s. 627-
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Tidskriftsartikel (refereegranskat)abstract
- This article reviews existing research at the intersection of genetics and economics, presents some new findings that illustrate the state of genoeconomics research, and surveys the prospects of this emerging field. Twin studies suggest that economic outcomes and preferences, once corrected for measurement error, appear to be about as heritable as many medical conditions and personality traits. Consistent with this pattern, we present new evidence on the heritability of permanent income and wealth. Turning to genetic association studies, we survey the main ways that the direct measurement of genetic variation across individuals is likely to contribute to economics, and we outline the challenges that have slowed progress in making these contributions. The most urgent problem facing researchers in this field is that most existing efforts to find associations between genetic variation and economic behavior are based on samples that are too small to ensure adequate statistical power. This has led to many false positives in the literature. We suggest a number of possible strategies to improve and remedy this problem: (a) pooling data sets, (b) using statistical techniques that exploit the greater information content of many genes jointly, and (c) focusing on economically relevant traits that are most proximate to known biological mechanisms.
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