Longevity candidate genes and their association with personality traits in the elderly.
ABSTRACT Human longevity and personality traits are both heritable and are consistently linked at the phenotypic level. We test the hypothesis that candidate genes influencing longevity in lower organisms are associated with variance in the five major dimensions of human personality (measured by the NEO-FFI and IPIP inventories) plus related mood states of anxiety and depression. Seventy single nucleotide polymorphisms (SNPs) in six brain expressed, longevity candidate genes (AFG3L2, FRAP1, MAT1A, MAT2A, SYNJ1, and SYNJ2) were typed in over 1,000 70-year old participants from the Lothian Birth Cohort of 1936 (LBC1936). No SNPs were associated with the personality and psychological distress traits at a Bonferroni corrected level of significance (P < 0.0002), but there was an over-representation of nominally significant (P < 0.05) SNPs in the synaptojanin-2 (SYNJ2) gene associated with agreeableness and symptoms of depression. Eight SNPs which showed nominally significant association across personality measurement instruments were tested in an extremely large replication sample of 17,106 participants. SNP rs350292, in SYNJ2, was significant: the minor allele was associated with an average decrease in NEO agreeableness scale scores of 0.25 points, and 0.67 points in the restricted analysis of elderly cohorts (most aged >60 years). Because we selected a specific set of longevity genes based on functional genomics findings, further research on other longevity gene candidates is warranted to discover whether they are relevant candidates for personality and psychological distress traits.
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ABSTRACT: Recently, it has been demonstrated that DNA methylation, a covalent modification of DNA that can regulate gene expression, is modified as a function of age. However, the biological and clinical significance of this age-associated epigenetic drift is unclear. To shed light on the potential biological significance, we here adopt a systems approach and study the genes undergoing age-associated changes in DNA methylation in the context of a protein interaction network, focusing on their topological properties. In contrast to what has been observed for other age-related gene classes, including longevity- and disease-associated genes, as well as genes undergoing age-associated changes in gene expression, we here demonstrate that age-associated epigenetic drift occurs preferentially in genes that occupy peripheral network positions of exceptionally low connectivity. In addition, we show that these genes synergize topologically with disease and longevity genes, forming unexpectedly large network communities. Thus, these results point toward a potentially distinct mechanistic and biological role of DNA methylation in dictating the complex aging and disease phenotypes.Proceedings of the National Academy of Sciences 08/2013; · 9.74 Impact Factor
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ABSTRACT: Background The leaves of the Coriandrum sativum plant, known as cilantro or coriander, are widely used in many cuisines around the world. However, far from being a benign culinary herb, cilantro can be polarizing—many people love it while others claim that it tastes or smells foul, often like soap or dirt. This soapy or pungent aroma is largely attributed to several aldehydes present in cilantro. Cilantro preference is suspected to have a genetic component, yet to date nothing is known about specific mechanisms. Results Here, we present the results of a genome-wide association study among 14,604 participants of European ancestry who reported whether cilantro tasted soapy, with replication in a distinct set of 11,851 participants who declared whether they liked cilantro. We find a single-nucleotide polymorphism (SNP) significantly associated with soapy-taste detection that is confirmed in the cilantro preference group. This SNP, rs72921001 (p = 6.4 × 10−9, odds ratio 0.81 per A allele), lies within a cluster of olfactory receptor genes on chromosome 11. Among these olfactory receptor genes is OR6A2, which has a high binding specificity for several of the aldehydes that give cilantro its characteristic odor. We also estimate the heritability of cilantro soapy-taste detection in our cohort, showing that the heritability tagged by common SNPs is low, about 0.087. Conclusions These results confirm that there is a genetic component to cilantro taste perception and suggest that cilantro dislike may stem from genetic variants in olfactory receptors. We propose that one of a cluster of olfactory receptor genes, perhaps OR6A2, may be the olfactory receptor that contributes to the detection of a soapy smell from cilantro in European populations.Flavour. 1(1).