Common variants near MC4R are associated with fat mass, weight and risk of obesity

To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) = 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits.     

Constitutional 11p15 abnormalities, including heritable imprinting center mutations, cause nonsyndromic Wilms tumor

Constitutional abnormalities at the imprinted 11p15 growth regulatory region cause syndromes characterized by disordered growth, some of which include a risk of Wilms tumor. We explored their possible contribution to nonsyndromic Wilms tumor and identified constitutional 11p15 abnormalities in genomic lymphocyte DNA from 13 of 437 individuals (3%) with sporadic Wilms tumor without features of growth disorders, including 12% of bilateral cases (P = 0.001) and in one familial Wilms tumor pedigree. No abnormality was detected in 220 controls (P = 0.006). Abnormalities identified included H19 DMR epimutations, uniparental disomy 11p15 and H19 DMR imprinting center mutations (one microinsertion and one microdeletion), thus identifying microinsertion as a new class of imprinting center mutation. Our data identify constitutional 11p15 defects as one of the most common known causes of Wilms tumor, provide mechanistic insights into imprinting disruption and reveal clinically important epigenotype-phenotype associations. The impact on clinical management dictates that constitutional 11p15 analysis should be considered in all individuals with Wilms tumor.     

Research on Environment-Economy CoordinationDevelopment Model

1IntroductionEnvironment-economycoordinationdevelopmentisoneofthemostconcernsatpresenttime.However,whatiscoordinationdevelopment,itsspecificationandthekindofitsmodelstructureetc.arestillunknown.Infact,coordinationdevelopmentissimplyaslogan.Thispaperrepresentsthattheultimategoalofenvironmentalprotectionandeconomicdevelopmentistomeetthedemandofpeople.Thisisdecidedbythesubjectivevalueofthenecessitiesfortotalmankinddevelopment.Mankindproducesphysicalsubstanceandundertakesenvironmentalprotection,b…     

Study on the REM Model for Group Decision Making

IntroductionAsocialchoicefunctionisamappingwhichassignsanonemptysubsetofthepotentialfeasiblesubsettoeachorderedpairconsistentofapotentialfeasiblesubsetofalternativesandascheduleorprofileofvoters'preferences.Consideranopinionaggregationprobleminwhichagroupofexpertsgivetheirscoresthatexpresstheirpreferencestoasetofalternativesanddesiretocombinetheirscoresintoasingleaggregationpreferenceoverthealternativeset.Theunderlyingideahereisthattheconsensusofnumerousexpertsresultsinasuperiorpreferenceonthe…     

COHERENT, REGULAR AND SIMPLE SYSTEMS IN ZERO DECOMPOSITIONS OF PARTIAL DIFFERENTIAL SYSTEMS

1.IntroductionWeareconcernedwithalgebraicdifferentialpolynomials(abbreviatedas'd-pcis)inafinitenumberofdifferentialindeterminatesoveradifferentialfieldofcharacteristic0.Givenafinitesetofsuchd-pcis,wewouldliketostudyd-Zero(),thedifferentialalgebraicsetdefinedbyPoverauniversaldifferentialfield.Wemayaskwhetherd-Zero()isempty,whetherad-pcivanishesond-Zero()(differentialradicalidealmembershipproblem),whatthedimensionofd-Zero()is,howtodecomposed-Zero()intoirreduciblealgebraicdifferentialsets,andso…     

METHODS OF ESTIMATION FOR QUASI-INDEPENDENCE IN CONTINGENCY TABLES

1.IntroductionAnUInberofauthorshaveconsideredtheproblemoffittingmodelsofquasi-independencetocontingenCytabledatawhichareeithertriangUlarorhaveanexcludeddiagonal.hithispaperthevariousmethodsproposedforfittingthesemodelsarecompared.ItisthenshoWnthstparameterestimatesarethesamefordifferentmodelsinsomecases.Anew,verysample,easytoimplemeDtalgoritlunispreseDted.Finallysomepreviousiterstivemethodsarecomparedwiththenewmethod.2.Quasi-IndependenceModeisforContingencyamblesSupposethatatwo-waycolltin…     

THE SELF-STABLE REGION APPROACH FOR SECOND ORDER SYSTEMS

1.IntroductionThecolltrolproblemofnonlinearuncertainsystemshasbeenextensivelyresearchedformanyyears.Manymethodshavebeenproposedandsomeprogresshasbeenmade.[1]poiedsoutthatsomesecondordersystemshaveaninherelltpropertythatthereexistscertainregioninwhichalltrajectoriesofthesystemremaininginitaftercertaintimeTwillconvergetotheorigin.Basedonthisproperty,anewapproachhajsbeenputforwardtoconstructacolltinuousfeedbacklawsuchthatallsystem'strajectoriesmovetowardtheregionandeventuallyremaininit.In[2,3],a…     

An Adaptive Identification and Control Scheme Using Radial Basis Function Networks

1.INTaODUCTIONThemultilayerfeedforwardneuralnetworks(MFNN)hasbeenwidelyappliedinmanyfieldssuchaspatternrecognition,nonlinearoptimization,systemidentificationandcontrol.Thesimpleback-propagation(BP)learningalgorithmisusuallyadoptedtoupdateitsweights.TheBPalgorithm,however,suffersdrawbacksofslowconvergenceandunpredictablesolutionsduringlearning.Althoughmailyapproachessuchasvariablestepsize,conjugategradient,pseudo-Newtonmethods[4]andothermethods[3,10],havebeendevelopedtoovercometheproble…     

Truncating mutations in the Fanconi anemia J gene BRIP1 are low-penetrance breast cancer susceptibility alleles

We identified constitutional truncating mutations of the BRCA1-interacting helicase BRIP1 in 9/1,212 individuals with breast cancer from BRCA1/BRCA2 mutation-negative families but in only 2/2,081 controls (P = 0.0030), and we estimate that BRIP1 mutations confer a relative risk of breast cancer of 2.0 (95% confidence interval = 1.2-3.2, P = 0.012). Biallelic BRIP1 mutations were recently shown to cause Fanconi anemia complementation group J. Thus, inactivating truncating mutations of BRIP1, similar to those in BRCA2, cause Fanconi anemia in biallelic carriers and confer susceptibility to breast cancer in monoallelic carriers.