6 results on '"Paterson, Andrew D."'
Search Results
2. A genome-wide linkage study of autism spectrum disorder and the broad autism phenotype in extended pedigrees.
- Author
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Woodbury-Smith M, Paterson AD, O'Connor I, Zarrei M, Yuen RKC, Howe JL, Thompson A, Parlier M, Fernandez B, Piven J, Scherer SW, Vieland V, and Szatmari P
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Bayes Theorem, Canada, Child, Child, Preschool, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Infant, Male, Middle Aged, Pedigree, Phenotype, United States, White People genetics, Young Adult, Autism Spectrum Disorder genetics, Chromosomes genetics, Genetic Linkage
- Abstract
Background: Although several genetic variants for autism spectrum disorder (ASD) have now been identified, these largely occur sporadically or are de novo. Much less progress has been made in identifying inherited variants, even though the disorder itself is familial in the majority of cases. The objective of this study was to identify chromosomal regions that harbor inherited variants increasing the risk for ASD using an approach that examined both ASD and the broad autism phenotype (BAP) among a unique sample of extended pedigrees., Methods: ASD and BAP were assessed using standardized tools in 28 pedigrees from Canada and the USA, each with at least three ASD-diagnosed individuals from two nuclear families. Genome-wide linkage analysis was performed using the posterior probability of linkage (PPL) statistic, a quasi-Bayesian method that provides strength of evidence for or against linkage in an essentially model-free manner, with outcomes on the probability scale., Results: The results confirm appreciable interfamilial heterogeneity as well as a high level of intrafamilial heterogeneity. Both ASD and combined ASD/BAP specific loci are apparent., Conclusions: Inclusion of subclinical phenotypes such as BAP should be more widely employed in genetic studies of ASD as a way of identifying inherited genetic variants for the disorder. Moreover, the results underscore the need for approaches to identifying genetic risk factors in extended pedigrees that are robust to high levels of inter/intrafamilial locus and allelic heterogeneity.
- Published
- 2018
- Full Text
- View/download PDF
3. Identification of a novel percent mammographic density locus at 12q24.
- Author
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Stevens KN, Lindstrom S, Scott CG, Thompson D, Sellers TA, Wang X, Wang A, Atkinson E, Rider DN, Eckel-Passow JE, Varghese JS, Audley T, Brown J, Leyland J, Luben RN, Warren RM, Loos RJ, Wareham NJ, Li J, Hall P, Liu J, Eriksson L, Czene K, Olson JE, Pankratz VS, Fredericksen Z, Diasio RB, Lee AM, Heit JA, DeAndrade M, Goode EL, Vierkant RA, Cunningham JM, Armasu SM, Weinshilboum R, Fridley BL, Batzler A, Ingle JN, Boyd NF, Paterson AD, Rommens J, Martin LJ, Hopper JL, Southey MC, Stone J, Apicella C, Kraft P, Hankinson SE, Hazra A, Hunter DJ, Easton DF, Couch FJ, Tamimi RM, and Vachon CM
- Subjects
- Aged, Breast Neoplasms epidemiology, Cohort Studies, Female, Genome-Wide Association Study, Humans, Mammary Glands, Human radiation effects, Mammography, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, T-Box Domain Proteins genetics, United States epidemiology, White People genetics, Breast Neoplasms diagnostic imaging, Breast Neoplasms genetics, Chromosomes, Human, Pair 12 genetics, Mammary Glands, Human chemistry
- Abstract
Percent mammographic density adjusted for age and body mass index (BMI) is one of the strongest risk factors for breast cancer and has a heritable component that remains largely unidentified. We performed a three-stage genome-wide association study (GWAS) of percent mammographic density to identify novel genetic loci associated with this trait. In stage 1, we combined three GWASs of percent density comprised of 1241 women from studies at the Mayo Clinic and identified the top 48 loci (99 single nucleotide polymorphisms). We attempted replication of these loci in 7018 women from seven additional studies (stage 2). The meta-analysis of stage 1 and 2 data identified a novel locus, rs1265507 on 12q24, associated with percent density, adjusting for age and BMI (P = 4.43 × 10(-8)). We refined the 12q24 locus with 459 additional variants (stage 3) in a combined analysis of all three stages (n = 10 377) and confirmed that rs1265507 has the strongest association in the 12q24 region (P = 1.03 × 10(-8)). Rs1265507 is located between the genes TBX5 and TBX3, which are members of the phylogenetically conserved T-box gene family and encode transcription factors involved in developmental regulation. Understanding the mechanism underlying this association will provide insight into the genetics of breast tissue composition.
- Published
- 2012
- Full Text
- View/download PDF
4. Were genome-wide linkage studies a waste of time? Exploiting candidate regions within genome-wide association studies.
- Author
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Yoo YJ, Bull SB, Paterson AD, Waggott D, and Sun L
- Subjects
- Computer Simulation, Diabetes Mellitus, Type 2 epidemiology, Finland epidemiology, Genetic Predisposition to Disease genetics, Humans, Models, Genetic, Models, Statistical, Polymorphism, Single Nucleotide, Research Design, United States epidemiology, Diabetes Mellitus, Type 2 genetics, Genetic Linkage, Genome, Human, Genome-Wide Association Study
- Abstract
A central issue in genome-wide association (GWA) studies is assessing statistical significance while adjusting for multiple hypothesis testing. An equally important question is the statistical efficiency of the GWA design as compared to the traditional sequential approach in which genome-wide linkage analysis is followed by region-wise association mapping. Nevertheless, GWA is becoming more popular due in part to cost efficiency: commercially available 1M chips are nearly as inexpensive as a custom-designed 10 K chip. It is becoming apparent, however, that most of the on-going GWA studies with 2,000-5,000 samples are in fact underpowered. As a means to improve power, we emphasize the importance of utilizing prior information such as results of previous linkage studies via a stratified false discovery rate (FDR) control. The essence of the stratified FDR control is to prioritize the genome and maintain power to interrogate candidate regions within the GWA study. These candidate regions can be defined as, but are by no means limited to, linkage-peak regions. Furthermore, we theoretically unify the stratified FDR approach and the weighted P-value method, and we show that stratified FDR can be formulated as a robust version of weighted FDR. Finally, we demonstrate the utility of the methods in two GWA datasets: Type 2 diabetes (FUSION) and an on-going study of long-term diabetic complications (DCCT/EDIC). The methods are implemented as a user-friendly software package, SFDR. The same stratification framework can be readily applied to other type of studies, for example, using GWA results to improve the power of sequencing data analyses., (2009 Wiley-Liss, Inc.)
- Published
- 2010
- Full Text
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5. Follow-up analysis of genome-wide association data identifies novel loci for type 1 diabetes.
- Author
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Grant SF, Qu HQ, Bradfield JP, Marchand L, Kim CE, Glessner JT, Grabs R, Taback SP, Frackelton EC, Eckert AW, Annaiah K, Lawson ML, Otieno FG, Santa E, Shaner JL, Smith RM, Skraban R, Imielinski M, Chiavacci RM, Grundmeier RW, Stanley CA, Kirsch SE, Waggott D, Paterson AD, Monos DS, Polychronakos C, and Hakonarson H
- Subjects
- Adolescent, Adult, Canada, Child, Child, Preschool, Cohort Studies, Genotype, Humans, Infant, Meta-Analysis as Topic, United States, Young Adult, Diabetes Mellitus, Type 1 genetics, Genetic Predisposition to Disease genetics, Genome-Wide Association Study methods, Polymorphism, Single Nucleotide
- Abstract
Objective: Two recent genome-wide association (GWA) studies have revealed novel loci for type 1 diabetes, a common multifactorial disease with a strong genetic component. To fully utilize the GWA data that we had obtained by genotyping 563 type 1 diabetes probands and 1,146 control subjects, as well as 483 case subject-parent trios, using the Illumina HumanHap550 BeadChip, we designed a full stage 2 study to capture other possible association signals., Research Design and Methods: From our existing datasets, we selected 982 markers with P < 0.05 in both GWA cohorts. Genotyping these in an independent set of 636 nuclear families with 974 affected offspring revealed 75 markers that also had P < 0.05 in this third cohort. Among these, six single nucleotide polymorphisms in five novel loci also had P < 0.05 in the Wellcome Trust Case-Control Consortium dataset and were further tested in 1,303 type 1 diabetes probands from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) plus 1,673 control subjects., Results: Two markers (rs9976767 and rs3757247) remained significant after adjusting for the number of tests in this last cohort; they reside in UBASH3A (OR 1.16; combined P = 2.33 x 10(-8)) and BACH2 (1.13; combined P = 1.25 x 10(-6))., Conclusions: Evaluation of a large number of statistical GWA candidates in several independent cohorts has revealed additional loci that are associated with type 1 diabetes. The two genes at these respective loci, UBASH3A and BACH2, are both biologically relevant to autoimmunity.
- Published
- 2009
- Full Text
- View/download PDF
6. Assessing the validity of the association between the SUMO4 M55V variant and risk of type 1 diabetes.
- Author
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Qu H, Bharaj B, Liu XQ, Curtis JA, Newhook LA, Paterson AD, Hudson TJ, and Polychronakos C
- Subjects
- Age of Onset, Case-Control Studies, Child, Diabetes Mellitus, Type 1 ethnology, Genetic Predisposition to Disease, Humans, United States, White People, Diabetes Mellitus, Type 1 genetics, Polymorphism, Single Nucleotide, Small Ubiquitin-Related Modifier Proteins genetics
- Published
- 2005
- Full Text
- View/download PDF
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