Bernie Devlin

..Our analysis suggests that it will be important to understand the basis for these maternal effects if ways in which IQ might be increased are to be identified...

..Naturally, as for any method seeking to explore complex genetic models, the power of the methods is limited by sample size and model complexity...

..50, P = 0.00035). By comparing our results to those implemented using more standard linkage methods, we find the covariates convey substantial information for the linkage analysis...

..For each study design our goal is to achieve control similar to that obtained for a family-based study, but with the convenience found in a population-based design...

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..1% less). Palauan Y haplotypes also fall into distinct clusters, again unlike that of Europe. We argue these data are consistent with waves of male-biased gene flow...

..The performance of our genomic control method is quite good for plausible effects of liability genes, which bodes well for future genetic analyses of complex disorders...

..It, too, is widely applicable. Both also have weaknesses, as elaborated in our review...

..Linkage results appear in a subsequent report. Our report lays out a systematic roadmap for utilizing a rich set of phenotypes for genetic analyses, including the selection of linkage methods paired to those phenotypes...

..Our aim was to explore the nature of the co-morbid relation between AUDs and eating disorders in a large and phenotypically well-characterized group of individuals...

..The results are plausible, based on prior studies of circadian abnormalities. As replications have not been attempted uniformly, we evaluated representative, common polymorphisms in all three disorders...

..Our recent studies in Egypt have shown elevated parental consanguinity rates among patients with bipolar I disorder (BP1), compared with controls. We have now extended our analyses to schizophrenia (SZ) in the same population...

..Regions in which at least two adjacent markers produced substantial association statistics include 2p12-11.2, 2q24.1-32.1, 6q12-14.1, 10q23.2-24.21, 12q23.2-24.21 and 17q23.2-23.3...

..Our data suggest that a network of dopaminergic polymorphisms increase risk for SZ...

..A liability locus might be in linkage disequilibrium (LD) with or carried against, an associated haplotype 3' to rs6280. Comprehensive SNP evaluation in larger samples is needed...

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..3); for covariate-based linkage analysis, five suggestive signals (for BMI at 4q13.1, for CM at 11p11.2 and 17q25.1, and for OBF at 17q25.1 and 15q26.2). Overlap between the two cohorts was minimal for substantial linkage signals...

..Future studies investigating EN2 should consider how the association of variants in this gene with autism could be influenced by differences in phenotype and possible interactions with genotypes at other autism candidate genes...

..Neither is significantly associated with Reelin alleles. Our results are not consistent with a major role for Reelin alleles in liability to autism...

..When the method is applied to data obtained from the Wellcome Trust Case Control Consortium study of Type 1 Diabetes it uncovers evidence supporting interaction within the HLA class II region as well as within Chromosome 12q24...

..There are a number of explanations for the associations, including chance variation, as well as gene-virus interactions. Further replicate studies are warranted, as are functional studies of these polymorphisms...

..047, OR = 1.46). Our analyses suggest several associations at PAH, with consistent evidence for rs1522305. Further analyses, including additional variations and environmental influences such as phenylalanine exposure are warranted...

..Supported by National Institute of Mental Health (NIMH), this 12-site international collaboration seeks to identify genetic variants that affect risk for anorexia nervosa (AN)...

..The latter suggests greater power can be achieved by specifying more complex genetic models, but this observation only follows when such models are largely correct and specified a priori...

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..Our findings do not support the association of poly-T repeat length with age of onset in LOAD. The clinical implications of this repeat length polymorphism remain to be elucidated...

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..Often the results from Spectral-GEM are straightforward to interpret and therefore useful in association analysis. We illustrate the new algorithm with an analysis of the POPRES data [Nelson et al., 2008]...

..The current study presents the clinical characteristics of this sample as well as a description of the study methodology...

..Published data support genetic variants, as well as certain infectious agents, as potential risk factors for schizophrenia. Less is known about interactions between the risk factors...

..Once samples are well-matched, mCLR yields comparable power to competing methods while ensuring excellent control over Type I error...

..We perform a GWA by matching Americans with type 1 diabetes (T1D) to controls from Germany. Despite the complex study design, these analyses identify numerous loci known to confer risk for T1D...

..Each gene was thoroughly interrogated with tag single-nucleotide polymorphisms (SNPs), and gene-based tests were used to enhance power. We found no association of these genes with AD + P...

..Yet, similar to other SCZ candidate genes, studies have been inconsistent with respect to the associated alleles...

..We use eigenvector transformations that maximize heritability of multiple neurocognitive measures, namely principal components of heritability (PCH), and evaluate how they distribute in SZ families and controls...

..Thus, distinct patterns of M/E were noted among BD1 patients and among BD1 subgroups. The impact of medication, mood state, and chronicity on CS scores needs to be considered...

..g., 3q28) appear to be novel results for schizophrenia linkage analyses...

..Self-reported estimates of consanguinity are bolstered by DNA-based estimates, and both show significant case-control differences for BP1...

..We therefore used latent class modeling to characterize trajectories of cognitive and behavioral decline in a cohort of AD subjects...

..We also propose a new, efficient method to select SNPs for association analysis, namely tag SNPs. These methods compare favorably to similar blocking and tagging methods using simulations...

..This cross-validation approach maintains the type I error control and yet utilizes the data efficiently, resulting in a powerful test for association...

..Finally, when a SNP selection procedure that targets a minimal number of SNPs per gene is applied, the average performances of T(P) and T(R) are indistinguishable...

..More importantly, our results show that, when multiple polymorphisms are found within the gene, the ET-TDT can be useful for determining which polymorphisms affect liability...

..The authors sought to assess the relationship between candidate genes and two clinical outcomes, namely, symptomatic improvement and the occurrence of suicidal events, in a sample of treatment-resistant depressed adolescents...

..Therefore, although we cannot exclude the possibility that the samples in the two studies are intrinsically different, our data from our sample argue against a major role for HOXA1 (His)73(Arg) in liability to autism...

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..Determining the factors influencing the relationship between autism phenotypes and HTTLPR variation, as well as other loci in SLC6A4, could be an important advance in our understanding of this complex disorder...

..Psychotic symptoms in patients with AD (AD with psychosis [AD+P]) define a phenotype characterized by more rapid cognitive and functional decline and a liability to aggressive behaviors...

..This map will help assess this gene-rich region in PGL and in other common tumours...

..By analysis of simulated data, we highlight how the hierarchical model, as implemented in the publicly available program AllDist, combines prior information with the observed data to refine allele frequency estimates...

..Thus, we confined PGL1 to an approximately 1.5 Mb region between D11S1986 and D11S1347, and showed identity-by-descent sharing for a group of American PGL families...

..Therefore, GC methods should prove a useful complement to family-based methods for the genetic analysis of complex traits...

..These findings indicate that mitochondria play an important role in the pathogenesis of certain tumors and that cybS plays a role in normal CB physiology...

..Examination of variation at ERE6 in subjects with schizophrenia, and further examination of the independent and additive effects of variations in COMT on gene expression, is warranted...

..In conclusion, we precisely mapped and characterized the structure of PPP2R1B and evaluated it as a candidate gene for PGL1...

..Thus far, evidence for association between specific SNPs at the circadian gene loci and BD1 is tentative. Additional studies using larger samples are required to evaluate the associations reported here...

..We discuss possible genetic models of psychotic symptoms in AD, and suggest strategies for further investigation. Identification of such genetic factors may facilitate gene-mapping studies for both AD and idiopathic psychoses...

..These results could partially explain the high frequency of alcohol-related pancreatitis in men (male hemizygote frequency is 0.26, whereas female homozygote frequency is 0.07)...

..abstract:..

..CONCLUSION: Multiplicity of symptoms may represent a useful means for defining a genetically determined LOAD+P phenotype...

..We lay out this theory, calculate plausible distributions, and discuss the results in the context of results from GWA studies for schizophrenia...

..Overall, our results, albeit not definitive, are consistent with the hypothesis that variants in MAOA account for a small portion of the variance of SUD risk, possibly mediated by liability to early onset behavioral problems...

..We show that both approaches can be powerful, but under quite different conditions. Moreover, we show that the power of both approaches can be enhanced by clustering rare haplotypes from the distributions before performing a test...

..The liability to addiction has been shown to be highly genetically correlated across drug classes, suggesting nondrug-specific mechanisms...

..Identification of ASD risk genes with high penetrance will broaden the targets amenable to genetic testing; while the biological pathways revealed by the deeper list of ASD genes should narrow the targets for therapeutic intervention...

..Our results illustrate the potential power of combining gene expression profiling and genomic analyses to identify susceptibility genes for genetically complex disorders...

..Such studies may advance us toward the goal of personalized treatment in late-life depression...

..This suggests that the DAT gene has followed different evolutionary trajectories during primate speciation...

..Similar symptom dimensions are apparent in childhood and adolescence, but their functional neural correlates remain to be elucidated...

..The exploratory analyses, such as error checking, estimation of haplotype frequencies, and tools for building cladograms, should facilitate the implementation of cladistic-based association analysis with haplotypes...

..Linkage analysis of families with LOAD+P identified one significant and several suggestive novel linkage signals, which bolsters the conjecture of greater etiologic homogeneity...

..92 and 3.39, meet the widely accepted criterion for genomewide significance. Another region on 14q meets the criterion for genomewide suggestive linkage, with MLSs of 1.97 (full sample) and 1.75 (subset) at 62 centimorgans from p-ter...

..Similar to the results for other populations, our results suggest there are multiple genes conferring liability to schizophrenia even in the small population of Palau (roughly 21,000 individuals) in remote Oceania...

..By enhancing our understanding of molecular genetic etiology, such methods will help us to understand disease processes better and will advance the promise of personalized medicine...

..This inquiry reveals that, among genetic models that are seemingly equal in genetic information, some are much more promising than others for this mode of analysis...

..If no groups show apparent signals, then the weights will be approximately equal. The only restriction on the procedure is that the number of groups be small, relative to the total number of tests performed...

..Our results suggest that NRG1 plays a role in increasing the genetic risk to positive symptoms of psychosis in a proportion of LOAD families...

..Genetically transmitted variation in D2 dopamine receptor expression mediated by functional polymorphisms affecting transcription and translation efficiency may play a role in vulnerability to AN...

..This study compares personality characteristics among women who are ill with eating disorders, recovered from eating disorders, and those without eating or other Axis I disorder pathology...

..Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs...

..These observations diminish the possibility that loci in the TOMM40 gene may have a major effect on the risk for LOAD in Caucasians...

..We demonstrate the feasibility of this molecular haplotyping procedure by generating apolipoprotein E (APOE) haplotypes from 100 unrelated subjects...

..This novel integration of diagnostic, neurocognitive and genetic data will also generate valuable information for future phenotypic and genetic studies of schizophrenia...