INFLUENCE OF CONTROL SELECTION IN GENOME-WIDE ASSOCIATION STUDY: THE EXAMPLE OF DIABETES IN THE FRAMIGHAM HEART STUDY.

International audienc

GÉNÉTIQUE ET ÉPIGÉNÉTIQUE DU COMPORTEMENT SOCIAL

International audienc

Aging and DNA methylation

International audienc

EXPLORATION DES FONCTIONS IMMUNOSUPPRESSIVES DES ARN NON CODANTS CONTENUS DANS LES EXOSOMES DU MÉLANOME

National audienc

T2DM: Why Epigenetics?

Type 2 Diabetes Mellitus (T2DM) is a metabolic disorder influenced by interactions between genetic and environmental factors. Epigenetics conveys specific environmental influences into phenotypic traits through a variety of mechanisms that are often installed in early life, then persist in differentiated tissues with the power to modulate the expression of many genes, although undergoing time-dependent alterations. There is still no evidence that epigenetics contributes significantly to the causes or transmission of T2DM from one generation to another, thus, to the current environment-driven epidemics, but it has become so likely, as pointed out in this paper, that one can expect an efflorescence of epigenetic knowledge about T2DM in times to come

Influence of control selection in genome-wide association studies: the example of diabetes in the Framingham Heart Study

Epidemiologic study designs represent a major challenge for genome-wide association studies. Most such studies to date have selected controls from the pool of participants without the disease of interest at the end of the study time. These choices can lead to biased estimates of exposure effects. Using data from the Framingham Heart Study (Genetic Analysis Workshop 16 Problem 2), we evaluate the impact on genetic association estimates for designs with control selection based on status at the end of a study (case exclusion (CE) sampling) to control selection based on incidence density (ID) sampling, when controls are selected from the pool of participants who are disease-free at the time a case is diagnosed. Cases are defined as those diagnosed with type 2 diabetes (T2D). We estimated odds ratios for 18 previously confirmed T2D variants using 189 cases selected by ID sampling and using 231 cases selected by CE sampling. We found none of these single-nucleotide polymorphisms to be significantly associated with T2D using either design. Because these empirical analyses were based on a small number of cases and on single-nucleotide polymorphisms with likely small effect sizes, we supplemented this work with simulated data sets of 500 cases from each strategies across a variety of allele frequencies and effect sizes. In our simulated datasets, we show ID sampling to be less biased than CE, although CE shows apparent increased power due to the upward bias of point estimates. We conclude that ID sampling is an appropriate option for genome-wide association studies

Three Common Variants of LEP, NPY1R and GPR54 Show No Association with Age at Menarche

International audienc

'Non-Mendelian' genetics of fetal growth

International audienceMendelian genetics showed that a few mutated genes, or errors in parental imprinting, can lead to major phenotypic changes (diseases) in pre-natal growth. Mendelian genetics, however, do not explain the individual subtle variability of size at birth within the normal range. Fetal growth is a complex multifactorial, multigenic trait made of various sub-traits, such as body mass, fat and muscle, brain mass, head circumference, skeletal growth of the spine and limbs. It is likely that multiple genetic factors and genomic variants are responsible for the variations of these sub-traits. A study has been launched to investigate the genetics of the variation of human birth weight, with the ultimate aim of identifying genomic variations that are within or near certain genes and are associated with variations of human height and weight at birth

Allele Dependent DNA Methylation of the Human Insulin Gene Promoter in T2D patients and Controls

International audienc

Personalized Epigenomic Signatures That Are Stable Over Time and Covary with Body Mass Index

International audienc