Asymptotically Exact, Embarrassingly Parallel MCMC

Communication costs, resulting from synchronization requirements during learning, can greatly slow down many parallel machine learning algorithms. In this paper, we present a parallel Markov chain Monte Carlo (MCMC) algorithm in which subsets of data are processed independently, with very little communication. First, we arbitrarily partition data onto multiple machines. Then, on each machine, any classical MCMC method (e.g., Gibbs sampling) may be used to draw samples from a posterior distribution given the data subset. Finally, the samples from each machine are combined to form samples from the full posterior. This embarrassingly parallel algorithm allows each machine to act independently on a subset of the data (without communication) until the final combination stage. We prove that our algorithm generates asymptotically exact samples and empirically demonstrate its ability to parallelize burn-in and sampling in several models

THE INFLUENCE OF FGFR1 VARIANTS ON NORMAL HUMAN CRANIOFACIAL SHAPE

The factors influencing the morphology of the human face are of interest to researchers in a variety of different fields. Craniofacial morphology is modified by both genetic and epigenetic events, and factors influencing craniofacial morphology include, but are not limited to, age, sex, mechanical function, soft-tissue matrices, hormones, and genetics. Mutations discovered within FGFR1 offer insight into the importance of this particular gene in controlling craniofacial skeletal development, and the evidence thus far connecting FGFR1 variants to quantitative craniofacial traits in the general population is inconclusive. The purpose of this study was to investigate the association between FGFR1 variants and several measures of cranial and facial shape in a sample of healthy human subjects and to serve as a replication sample for prior genotype-phenotype studies with positive findings for FGFR1. This study comprised 1375 subjects (544 Male, 795 Female, 36 unknown sex) recruited as part of the 3D Facial Norms Project. 3D facial surface images were captured using digital stereophotogrammetry and eight craniofacial measurements were analyzed: maximum cranial width, maximum cranial length, morphological face height, upper face height, nasal protrusion, cephalic index, facial index and upper facial index. Two SNP’s of FGFR1 were genotyped: rs6983315 (intronic variant) and rs13317 (3’ UTR variant). Genotype-phenotype associations were tested with linear regression, using an additive model and a full dominant model, where age and sex were included as covariates in all analyses. Results were considered significant if p ≤ 0.0015. No significant associations were observed between either of the two SNPs and any of the eight craniofacial measurements, and the association results of previous studies could not be replicated

The prevalence, penetrance, and expressivity of etiologic <i>IRF6</i> variants in orofacial clefts patients from sub-Saharan Africa

BACKGROUND: Orofacial clefts are congenital malformations of the orofacial region, with a global incidence of one per 700 live births. Interferon Regulatory Factor 6 (IRF6) (OMIM:607199) gene has been associated with the etiology of both syndromic and nonsyndromic orofacial clefts. The aim of this study was to show evidence of potentially pathogenic variants in IRF6 in orofacial clefts cohorts from Africa. METHODS: We carried out Sanger Sequencing on DNA from 184 patients with nonsyndromic orofacial clefts and 80 individuals with multiple congenital anomalies that presented with orofacial clefts. We sequenced all the nine exons of IRF6 as well as the 5′ and 3′ untranslated regions. In our analyses pipeline, we used various bioinformatics tools to detect and describe the potentially etiologic variants. RESULTS: We observed that potentially etiologic exonic and splice site variants were nonrandomly distributed among the nine exons of IRF6, with 92% of these variants occurring in exons 4 and 7. Novel variants were also observed in both nonsyndromic orofacial clefts (p.Glu69Lys, p.Asn185Thr, c.175‐2A>C and c.1060+26C>T) and multiple congenital anomalies (p.Gly65Val, p.Lys320Asn and c.379+1G>T) patients. Our data also show evidence of compound heterozygotes that may modify phenotypes that emanate from IRF6 variants. CONCLUSIONS: This study demonstrates that exons 4 and 7 of IRF6 are mutational ‘hotspots’ in our cohort and that IRF6 mutants‐induced orofacial clefts may be prevalent in the Africa population, however, with variable penetrance and expressivity. These observations are relevant for detection of high‐risk families as well as genetic counseling. In conclusion, we have shown that there may be a need to combine both molecular and clinical evidence in the grouping of orofacial clefts into syndromic and nonsyndromic forms