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Rare genetic variants contribute to complex disease risk; however, the abundance of rare variants in human populations remains unknown. We explored this spectrum of variation by sequencing 202 genes encoding drug targets in 14,002 individuals. We find rare variants are abundant (1 every 17 bases) and geographically localized, so that even with large sample(More)
BACKGROUND Research efforts to discover the genetic underpinnings of anxiety and depression is challenging because of the etiologic heterogeneity inherent to these disorders. These efforts might be aided by the study of related behavioral phenotypes in model organisms, such as monkeys. METHODS Eighty-five rhesus monkeys (Macaca mulatta) from the Oregon(More)
OBJECTIVE Psychotic symptoms in Alzheimer disease (AD) identify a phenotype with distinct neurobiology and genetic architecture. The authors investigated whether AD with psychosis is homogeneous or is a composite of subtypes. METHODS Authors performed factor and cluster analyses of the psychotic-symptom items of the CERAD Behavioral Rating Scale in 188(More)
A goal of association analysis is to determine whether variation in a particular candidate region or gene is associated with liability to complex disease. To evaluate such candidates, ubiquitous Single Nucleotide Polymorphisms (SNPs) are useful. It is critical, however, to select a set of SNPs that are in substantial linkage disequilibrium (LD) with all(More)
To investigate whether the dopaminergic system plays a role in the etiology of anorexia nervosa (AN) via the dopamine D2 receptor, we investigated association and transmission disequilibrium at seven single-nucleotide polymorphisms (SNPs) spanning about 75 kbp of the gene DRD2. We studied 191 probands with a DSM-IV diagnosis of AN, 457 parents and affected(More)
Schizophrenia (SCZ) and bipolar disorder (BPD) are severe mental disorders with high heritability. Clinicians have long noticed the similarities of clinic symptoms between these disorders. In recent years, accumulating evidence indicates some shared genetic liabilities. However, what is shared remains elusive. In this study, we conducted whole transcriptome(More)
Our aim was to identify genes that influence the inverse association of coffee with the risk of developing Parkinson's disease (PD). We used genome-wide genotype data and lifetime caffeinated-coffee-consumption data on 1,458 persons with PD and 931 without PD from the NeuroGenetics Research Consortium (NGRC), and we performed a genome-wide association and(More)
To increase the likelihood of finding genetic variation conferring liability to eating disorders, we measured over 100 attributes thought to be related to liability to eating disorders on affected individuals from multiplex families and two cohorts: one recruited through a proband with anorexia nervosa (AN; AN cohort); the other recruited through a proband(More)
Association between disease and genetic polymorphisms often contributes critical information in our search for the genetic components of common diseases. Devlin and Roeder [1999: Biometrics 55:997-1004] introduced genomic control, a statistical method that overcomes a drawback to the use of population-based samples for tests of association, namely spurious(More)
Linkage disequilibrium (LD) in the human genome, often measured as pairwise correlation between adjacent markers, shows substantial spatial heterogeneity. Congruent with these results, studies have found that certain regions of the genome have far less haplotype diversity than expected if the alleles at multiple markers were independent, while other sets of(More)