Classification de variables en régression linéaire

International audienceFor the last three decades, the advent of technologies for massive data collection have brought deep changes in many scientific fields. What was first seen as a blessing, rapidly turned out to be termed as the curse of dimensionality. Reducing the dimensionality has therefore become a challenge in statistical learning. In high dimensional linear regression models, the quest for parsimony has long been driven by the idea that a few relevant variables may be sufficient to describe the modeled phenomenon. Recently, a new paradigm was introduced in a series of articles from which the present work derives. We propose here a model that simultaneously performs variable clustering and regression. Our approach no longer considers the regression coefficients as fixed parameters to be estimated, but as unobserved random variables following a Gaussian mixture model. The latent partition is then determined by maximum likelihood and predictions are obtained from the conditional distribution of the regression coefficients given the data. The number of latent components is chosen using a BIC criterion. Our model has very competitive predictive performances compared to standard approaches and brings significant improvements in interpretability.Les trois dernières décennies ont vu l’avènement de profonds changements dans de nombreuses discipline scientifiques. Certains de ces changements, directement liés à la collecte massive de données, ont donné naissance à de nombreux défis en apprentissage statistique. La réduction de la dimension en est un. En régression linéaire, l’idée de parcimonie a longtemps été associée à la possibilité de modéliser un phénomène grâce à un faible nombre de variables. Un nouveau paradigme a récemment été introduit dans lequel s’inscrivent pleinement les présents travaux. Nous présentons ici un modèle permettant simultanément d’estimer un modèle de régression tout en effectuant une classification des covariables. Ce modèle ne considère pas les coefficients de régression comme des paramètres à estimer mais plutôt comme des variables aléatoires non observées suivant une distribution de mélange gaussien. La partition latente des variables est estimée par maximum de vraisemblance. Le nombre de groupes de variables est choisi en minimisant le critère BIC. Notre modèle possède une très bonne qualité de prédiction et son interprétation est aisée grâce à l’introduction de groupe de variables

Variable clustering in high dimensional linear regression models

International audienceFor the last three decades, the advent of technologies for massive data collection have brought deep changes in many scientific fields. What was first seen as a blessing, rapidly turned out to be termed as the curse of dimensionality. Reducing the dimensionality has therefore become a challenge in statistical learning. In high dimensional linear regression models, the quest for parsimony has long been driven by the idea that a few relevant variables may be sufficient to describe the modeled phenomenon. Recently, a new paradigm was introduced in a series of articles from which the present work derives. We propose here a model that simultaneously performs variable clustering and regression. Our approach no longer considers the regression coefficients as fixed parameters to be estimated, but as unobserved random variables following a Gaussian mixture model. The latent partition is then determined by maximum likelihood and predictions are obtained from the conditional distribution of the regression coefficients given the data. The number of latent components is chosen using a BIC criterion. Our model has very competitive predictive performances compared to standard approaches and brings significant improvements in interpretability

Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index

A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown. We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex-and age-adjusted standard deviation scores. We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value &lt;5 x 10(-8)) in the joint discovery and replication analysis, of which 12 are previously identified loci in or close to ADCY3, GNPDA2, TMEM18, SEC16B, FAIM2, FTO, TFAP2B, TNNI3K, MC4R, GPR61, LMX1B and OLFM4 associated with adult body mass index or childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) [Standard Error (SE) 0.007], 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503 and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 x 10(-10)) increase in childhood body mass index in a population of 1955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in strength of the associations with body mass index.</p

New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk

To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10−8), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms