Anthony L Hinrichs

..However, a fairly high rate of no-calls, especially for the Affymetrix platform, suggests that the inconsistency rate may be higher than observed...

..Furthermore, we have identified two single-nucleotide polymorphisms that may influence the expression of multiple genes linked to chromosome 14...

..We examine a generalization of principal-component analyses to allow for the inclusion of related individuals by down-weighting the significance of individual comparisons...

..These analyses were carried out without knowledge of the model used to generate the simulation...

..However, increased information has a computational cost: SNP maps require 100 times as many iterations as microsatellites to produce stable estimates...

..To determine whether genomic regions affecting this phenotype could be identified, we pursued a "model-free" multipoint quantitative linkage analysis...

..CIDR, Affymetrix, and Illumina provided single-nucleotide polymorphism genotyping of a large subset of the COGA subjects. This article briefly describes the dataset that was provided...

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..The challenge we address is to distinguish among these correlated loci to highlight potential functional variants and prioritize them for follow-up...

..The nonsynonymous SNP rs16969968, a known risk variant in populations of European-descent, is also significantly associated with risk in African-Americans. Additional SNPs contribute to risk in distinct ways in these two populations...

..The goal of this study was to examine the association of this variant with cocaine dependence...

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..In the present report, we extend the previous study by expanding our genotyping efforts significantly for these two genes...

..0 on chromosome 2 (3.2, 234 cM), 10 (2.4 and 2.6 at 60 cM and 116 cM) and 13 (2.1 at 64 cM). These regions may harbor genes that contribute to the biological basis of alcohol and drug dependence...

..This work anticipates the future directions of large-scale genome wide association studies with state-of-the-art methodological approaches and sharing of data with the scientific community...

..However, we cannot rule out the possibility that multiple rare variants that increase APP expression or Abeta production might influence the risk for LOAD...

..If SNPs with lower MAFs are used, then more than 250 SNPs may be required to obtain reliable results...

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..We also considered the effect of high linkage disequilibrium (LD) in regions near the linkage peaks by analysing a "sparse" SNP map obtained by dropping some markers in high LD with other markers in those regions...

..11 and 1.16. Further dissection of the alcoholism phenotype, to disentangle the influence of comorbid substance-use disorders, will be a next step in identifying genetic variants associated with alcohol dependence...

..There was no association with other genes in the GABAA cluster on chromosome 4 with illicit drug dependence...

..Rs1990622 (TMEM106B) was identified as a risk factor for frontotemporal lobar degeneration with TAR DNA-binding protein inclusions (FTLD-TDP) in a recent genome-wide association...

..Some of this clustering may be due to the presence of a second segregating SNP that obliterates a XbaI site (the restriction enzyme used in the Affymetrix platform), resulting in a fragment too long (>1,000 bp) to be amplified...

..A meta-analysis of two promoter SNPs, which combined the data from this study with two previous ones, did not show any association either suggesting that common SNPs in Pin1 do not increase the risk for LOAD...

..To study the association between cytochrome P450 2A6 (CYP2A6) genotype and metabolism of nicotine to cotinine, identify functional polymorphisms, and develop a predictive genetic model of nicotine metabolism...

..We did not find any evidence that this single nucleotide polymorphism, or any of six others tested in UBQLN1, increases risk for LOAD...

..6%), whereas 45% of African Americans carry the allele (MAF 26%), which makes it a much more significant risk factor in the African American population...

..3-p15.2, 5p15.2-q13.3, 10p15.3-p14, 10q25.3-q26.3, and 11p13-q23.3. The highest increase in Z(lr) scores was observed for 5p14.1-q12.1, where the maximum Z(lr) increased from 2.77 initially to 3.80 after fine mapping in the EA families...

..Other genes among the top signals were KCNJ6 and GABRA4. This study represents one of the most powerful and extensive studies of nicotine dependence to date and has found novel risk loci that require confirmation by replication studies...

..These findings provide strong evidence that variants within or close to the CHRM2 locus influence risk for two common psychiatric disorders...

..A better understanding of the etiology of nicotine addiction may help to increase the success rate of cessation and to decrease the massive morbidity and mortality associated with smoking...

..Imaging of Abeta deposition in the human brain using Pittsburgh Compound B (PIB) offers the possibility of using cortical PIB binding as a quantitative endophenotype for genetic studies of late-onset Alzheimer's disease (LOAD)...

..g., in chromosomal inversions). Our group also reported a method for performing an association test controlling for substructure, when genome-wide markers are not available, to explicitly compute stratification...

..Clearly, when pedigrees are available, they can provide great assistance in the search for rare variants that influence common disorders...

..We also assessed the aggregation of other psychiatric disorders in the same sample to identify areas of possible shared genetic vulnerability...

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..Although our results are not universally negative, we were unable to replicate the results of previous studies and conclude that common variants or haplotypes of these variants in IDE are not major risk factors for LOAD...

..Power and false-positive rates were evaluated using the first 100 replicate datasets. This included an exploration of the utility of using of all genotyped family members compared with selecting one member per family...

..0001. Eight of these SNPs (rs10498105, rs2398966, rs7664880, rs7447161, rs2793471, rs2611279, rs7967594, and rs742605) were common to both lists...

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..However, including population as a covariate was not an effective substitute for analyzing the subpopulations separately when only one subpopulation contained a rare variant linked to the phenotype...

..Finally, there is also evidence of an area on chromosome 2 that may reflect a common genetic vulnerability locus to both habitual smoking and alcohol dependence...

..These results, if confirmed, could lead to the personalization of SSRI use to reduce adverse neurocognitive effects...

..Using both methods, we found numerous significant linkage signals for Q1, although population colocalization was absent for most of these signals. The linkage analysis of Q2 and Q4 failed to reveal any strong linkage signals...