Long-chain n-3 polyunsaturated fatty acids (PUFAs) can derive from diet or from α-linolenic acid (ALA) by elongation and desaturation. We investigated the association of common genetic variation with plasma phospholipid levels of the four major n-3 PUFAs by performing genome-wide association studies in five population-based cohorts comprising 8,866 subjects of European ancestry. Minor alleles of SNPs in FADS1 and FADS2 (desaturases) were associated with higher levels of ALA (p = 3×10−64) and lower levels of eicosapentaenoic acid (EPA, p = 5×10−58) and docosapentaenoic acid (DPA, p = 4×10−154). Minor alleles of SNPs in ELOVL2 (elongase) were associated with higher EPA (p = 2×10−12) and DPA (p = 1×10−43) and lower docosahexaenoic acid (DHA, p = 1×10−15). In addition to genes in the n-3 pathway, we identified a novel association of DPA with several SNPs in GCKR (glucokinase regulator, p = 1×10−8). We observed a weaker association between ALA and EPA among carriers of the minor allele of a representative SNP in FADS2 (rs1535), suggesting a lower rate of ALA-to-EPA conversion in these subjects. In samples of African, Chinese, and Hispanic ancestry, associations of n-3 PUFAs were similar with a representative SNP in FADS1 but less consistent with a representative SNP in ELOVL2. Our findings show that common variation in n-3 metabolic pathway genes and in GCKR influences plasma phospholipid levels of n-3 PUFAs in populations of European ancestry and, for FADS1, in other ancestries.
Summary.We consider the problem of reconstructing prehistoric climates by using fossil data that have been extracted from lake sediment cores. Such reconstructions promise to provide one of the few ways to validate modern models of climate change. A hierarchical Bayesian modelling approach is presented and its use, inversely, is demonstrated in a relatively small but statistically challenging exercise: the reconstruction of prehistoric climate at Glendalough in Ireland from fossil pollen. This computationally intensive method extends current approaches by explicitly modelling uncertainty and reconstructing entire climate histories. The statistical issues that are raised relate to the use of compositional data (pollen) with covariates (climate) which are available at many modern sites but are missing for the fossil data. The compositional data arise as mixtures and the missing covariates have a temporal structure. Novel aspects of the analysis include a spatial process model for compositional data, local modelling of lattice data, the use, as a prior, of a random walk with long-tailed increments, a two-stage implementation of the Markov chain Monte Carlo approach and a fast approximate procedure for cross-validation in inverse problems. We present some details, contrasting its reconstructions with those which have been generated by a method in use in the palaeoclimatology literature. We suggest that the method provides a basis for resolving important challenging issues in palaeoclimate research. We draw attention to several challenging statistical issues that need to be overcome.
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