Large upward bias in estimation of locus-specific effects from genomewide scans.
paper
Cited
Public
Unavailable
- Authors
- GΓΆring, H H; Terwilliger, J D; Blangero, J
- Year
- 2001
- Journal
- American journal of human genetics
- PMID
- 11593451
- DOI
- 10.1086/324471
- PMCID
- PMC1235546
The primary goal of a genomewide scan is to estimate the genomic locations of genes influencing a trait of interest. It is sometimes said that a secondary goal is to estimate the phenotypic effects of each identified locus. Here, it is shown that these two objectives cannot be met reliably by use of a single data set of a currently realistic size. Simulation and analytical results, based on variance-components linkage analysis as an example, demonstrate that estimates of locus-specific effect size at genomewide LOD score peaks tend to be grossly inflated and can even be virtually independent of the true effect size, even for studies on large samples when the true effect size is small. However, the bias diminishes asymptotically. The explanation for the bias is that the LOD score is a function of the locus-specific effect-size estimate, such that there is a high correlation between the observed statistical significance and the effect-size estimate. When the LOD score is maximized over the many pointwise tests being conducted throughout the genome, the locus-specific effect-size estimate is therefore effectively maximized as well. We argue that attempts at bias correction give unsatisfactory results, and that pointwise estimation in an independent data set may be the only way of obtaining reliable estimates of locus-specific effect-and then only if one does not condition on statistical significance being obtained. We further show that the same factors causing this bias are responsible for frequent failures to replicate initial claims of linkage or association for complex traits, even when the initial localization is, in fact, correct. The findings of this study have wide-ranging implications, as they apply to all statistical methods of gene localization. It is hoped that, by keeping this bias in mind, we will more realistically interpret and extrapolate from the results of genomewide scans.
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|---|---|---|---|---|
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| Evaluating the roles of drift and selection in trait loss along an elevational gradient. | Buysse SF et al. | β | 2025 | β |
| Genetic regulation of sperm DNA methylation in cattle through meQTL mapping. | FouΓ©rΓ© C et al. | β | 2025 | β |
| Improving Replication in Endometrial Omics: Understanding the Influence of the Menstrual Cycle. | Chung J et al. | β | 2025 | β |
| Investigating Motor Coordination Using BXD Recombinant Inbred Mice to Model the Genetic Underpinnings of Developmental Coordination Disorder. | Rajan JRS et al. | β | 2025 | β |
| Regulation of heterosis-associated gene expression complementation in maize hybrids. | Pitz M et al. | β | 2025 | β |
| Trans-regulatory loci shape natural variation of gene expression plasticity in Arabidopsis. | Lensink M et al. | β | 2025 | β |
| Winner's curse in rare variant analysis: effect size estimation bias depends on effect direction and the association method used. | Soave D et al. | β | 2025 | β |
| Approaches to estimate bidirectional causal effects using Mendelian randomization with application to body mass index and fasting glucose. | Zou J et al. | β | 2024 | β |
| Glycemic traits and colorectal cancer survival in a cohort of South Korean patients: A Mendelian randomization analysis. | Jun SY et al. | β | 2024 | β |
| Body mass index and inflammation in depression and treatment-resistant depression: a Mendelian randomisation study. | Karageorgiou V et al. | β | 2023 | β |
| Candidate gene discovery of <i>Botrytis cinerea</i> resistance in grapevine based on QTL mapping and RNA-seq. | Su K et al. | β | 2023 | β |
| Conditional inference in cis-Mendelian randomization using weak genetic factors. | Patel A et al. | β | 2023 | β |
| Invited review: Good practices in genome-wide association studies to identify candidate sequence variants in dairy cattle. | Sahana G et al. | β | 2023 | β |
| Pervasive Sharing of Causal Genetic Risk Factors Contributes to Clinical and Molecular Overlap between SjΓΆgren's Disease and Systemic Lupus Erythematosus. | Chau K et al. | β | 2023 | β |
| Phenome-wide Mendelian randomization study of plasma triglyceride levels and 2600 disease traits. | Park JK et al. | β | 2023 | β |
| Review and further developments in statistical corrections for Winner's Curse in genetic association studies. | Forde A et al. | β | 2023 | β |
| DNA methylation signatures of Alzheimer's disease neuropathology in the cortex are primarily driven by variation in non-neuronal cell-types. | Shireby G et al. | β | 2022 | β |
| Estimating genetic variance contributed by a quantitative trait locus: A random model approach. | Wang S et al. | β | 2022 | β |
| Association of Genetic Variants With Body-Mass Index and Blood Pressure in Adolescents: A Replication Study. | Goulet D et al. | β | 2021 | β |
| Average semivariance yields accurate estimates of the fraction of marker-associated genetic variance and heritability in complex trait analyses. | Feldmann MJ et al. | β | 2021 | β |
| Estimation of genetic variance contributed by a quantitative trait locus: correcting the bias associated with significance tests. | Xie F et al. | β | 2021 | β |
| Genetic association with boldness and maternal performance in a free-ranging population of grey seals (Halichoerus grypus). | Bubac CM et al. | β | 2021 | β |
| High-Density Genetic Linkage Map Construction and White Rot Resistance Quantitative Trait Loci Mapping for Genus <i>Vitis</i> Based on Restriction Site-Associated DNA Sequencing. | Su K et al. | β | 2021 | β |
| Application of Mendelian Randomization to Investigate the Association of Body Mass Index with Health Care Costs. | Kurz CF et al. | β | 2020 | β |
| Distinct subtypes of polycystic ovary syndrome with novel genetic associations: An unsupervised, phenotypic clustering analysis. | Dapas M et al. | β | 2020 | β |
| Gene expression variability in human and chimpanzee populations share common determinants. | Fair BJ et al. | β | 2020 | β |
| High-density genetic linkage map construction and cane cold hardiness QTL mapping for Vitis based on restriction site-associated DNA sequencing. | Su K et al. | β | 2020 | β |
| Selective peak inference: Unbiased estimation of raw and standardized effect size at local maxima. | Davenport S et al. | β | 2020 | β |
| The MRC IEU OpenGWAS data infrastructure | Elsworth B et al. | β | 2020 | β |
| Docosapentaenoic acid and lung cancer risk: A Mendelian randomization study. | Liu J et al. | β | 2019 | β |
| Efficient estimation of disease odds ratios for follow-up genetic association studies. | Hu J et al. | β | 2019 | β |
| Evidence for Weak Selective Constraint on Human Gene Expression. | Glassberg EC et al. | β | 2019 | β |
| Measuring viability selection from prospective cohort mortality studies: A case study in maritime pine. | Robledo-Arnuncio JJ et al. | β | 2019 | β |
| Different Genomic Changes Underlie Adaptive Evolution in Populations of Contrasting History. | Seabra SG et al. | β | 2018 | β |
| Genotyping by Sequencing Highlights a Polygenic Resistance to Ralstonia pseudosolanacearum in Eggplant (Solanum melongena L.). | Salgon S et al. | β | 2018 | β |
| Height and overall cancer risk and mortality: evidence from a Mendelian randomisation study on 310,000 UK Biobank participants. | Ong JS et al. | β | 2018 | β |
| Plasma levels of hsa-miR-152-3p are associated with diabetic nephropathy in patients with type 2 diabetes. | Roux M et al. | β | 2018 | β |
| SNP-skimming: A fast approach to map loci generating quantitative variation in natural populations. | Wessinger CA et al. | β | 2018 | β |
| Association mapping of morphological traits in wild and captive zebra finches: reliable within, but not between populations. | Knief U et al. | β | 2017 | β |
| Effect of CLU and PICALM polymorphisms on AD risk: A study from south India. | Shankarappa BM et al. | β | 2017 | β |
| Genome-wide Association Study of Susceptibility to Particulate Matter-Associated QT Prolongation. | Gondalia R et al. | β | 2017 | β |
| Illustrating, Quantifying, and Correcting for Bias in Post-hoc Analysis of Gene-Based Rare Variant Tests of Association. | Grinde KE et al. | β | 2017 | β |
| The Beavis Effect in Next-Generation Mapping Panels in <i>Drosophila melanogaster</i>. | King EG et al. | β | 2017 | β |
| The earth is flat (<i>p</i>Β >Β 0.05): significance thresholds and the crisis of unreplicable research. | Amrhein V et al. | β | 2017 | β |
| What can genome-wide association studies tell us about the evolutionary forces maintaining genetic variation for quantitative traits? | Josephs EB et al. | β | 2017 | β |
| An Overview of Genome-Wide Association Studies in Alzheimer's Disease. | Shen L et al. | β | 2016 | β |
| Best (but oft-forgotten) practices: the design, analysis, and interpretation of Mendelian randomization studies. | Haycock PC et al. | β | 2016 | β |
| Common and rare forms of diabetes mellitus: towards a continuum of diabetes subtypes. | Flannick J et al. | β | 2016 | β |
| Detecting Polygenic Evolution: Problems, Pitfalls, and Promises. | Wellenreuther M et al. | β | 2016 | β |
| Power estimation and sample size determination for replication studies of genome-wide association studies. | Jiang W et al. | β | 2016 | β |
| Using local multiplicity to improve effect estimation from a hypothesis-generating pharmacogenetics study. | Zou W et al. | β | 2016 | β |
| Whole-genome resequencing of extreme phenotypes in collared flycatchers highlights the difficulty of detecting quantitative trait loci in natural populations. | Kardos M et al. | β | 2016 | β |
| Genetic Variants Influencing Joint Damage in Mexican Americans and European Americans With Rheumatoid Arthritis. | Arya R et al. | β | 2015 | β |
| Genome-wide association and functional studies identify a role for IGFBP3 in hip osteoarthritis. | Evans DS et al. | β | 2015 | β |
| Resampling to Address the Winner's Curse in Genetic Association Analysis of Time to Event. | Poirier JG et al. | β | 2015 | β |
| The genetic architecture of sexually selected traits in two natural populations of Drosophila montana. | Veltsos P et al. | β | 2015 | β |
| When is it MODY? Challenges in the Interpretation of Sequence Variants in MODY Genes. | Althari S et al. | β | 2015 | β |
| A genome-wide supported variant in CACNA1C influences hippocampal activation during episodic memory encoding and retrieval. | Krug A et al. | β | 2014 | β |
| ALDH2 is associated to alcohol dependence and is the major genetic determinant of "daily maximum drinks" in a GWAS study of an isolated rural Chinese sample. | Quillen EE et al. | β | 2014 | β |
| Epigenetic alteration of the dopamine transporter gene in alcohol-dependent patients is associated with age. | Nieratschker V et al. | β | 2014 | β |
| Genetic architecture of skeletal evolution in European lake and stream stickleback. | Berner D et al. | β | 2014 | β |
| Integrated phenotypes: understanding trait covariation in plants and animals. | Armbruster WS et al. | β | 2014 | β |
| Mendelian randomization in health research: using appropriate genetic variants and avoiding biased estimates. | Taylor AE et al. | β | 2014 | β |
| Assessing the phenotypic effects in the general population of rare variants in genes for a dominant Mendelian form of diabetes. | Flannick J et al. | β | 2013 | β |
| Complex rare variation and its role in endophenotypic variation in schizophrenia. | Blangero J | β | 2013 | β |
| From beavis to beak color: a simulation study to examine how much qtl mapping can reveal about the genetic architecture of quantitative traits. | Slate J | β | 2013 | β |
| Gene Γ physical activity interactions in obesity: combined analysis of 111,421 individuals of European ancestry. | Ahmad S et al. | β | 2013 | β |
| [Genetics and Alzheimer's disease: a population at risk]. | FernΓ‘ndez-Viadero C et al. | β | 2013 | β |
| Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus. | Lu Y et al. | β | 2013 | β |
| Genome-wide association study of patient-rated and clinician-rated global impression of severity during antipsychotic treatment. | Clark SL et al. | β | 2013 | β |
| Impacts of population structure and analytical models in genome-wide association studies of complex traits in forest trees: a case study in Eucalyptus globulus. | Cappa EP et al. | β | 2013 | β |
| Imprints of natural selection along environmental gradients in phenology-related genes of Quercus petraea. | Alberto FJ et al. | β | 2013 | β |
| Mendelian randomization analysis with multiple genetic variants using summarized data. | Burgess S et al. | β | 2013 | β |
| Parametric estimation of the local false discovery rate for identifying genetic associations. | Yang Y et al. | β | 2013 | β |
| Partitioning of genetic variation across the genome using multimarker methods in a wild bird population. | Robinson MR et al. | β | 2013 | β |
| Polymorphisms in genes involved in folate metabolism modify the association of dietary and circulating folate and vitamin B-6 with cervical neoplasia. | Tomita LY et al. | β | 2013 | β |
| Re-ranking sequencing variants in the post-GWAS era for accurate causal variant identification. | Faye LL et al. | β | 2013 | β |
| Statistical testing of shared genetic control for potentially related traits. | Wallace C | β | 2013 | β |
| A genome-wide association study of osteochondritis dissecans in the Thoroughbred. | Corbin LJ et al. | β | 2012 | β |
| A genome-wide linkage study of individuals with high scores on NEO personality traits. | Amin N et al. | β | 2012 | β |
| Comparing linkage and association analyses in sheep points to a better way of doing GWAS. | Kemper KE et al. | β | 2012 | β |
| Evaluating the evidence for transmission distortion in human pedigrees. | Meyer WK et al. | β | 2012 | β |
| Genetic modifiers of nutritional status in cystic fibrosis. | Bradley GM et al. | β | 2012 | β |
| Genetic variants near PDGFRA are associated with corneal curvature in Australians. | Mishra A et al. | β | 2012 | β |
| Genome-wide analysis of epistasis in body mass index using multiple human populations. | Wei WH et al. | β | 2012 | β |
| Genome-wide association study of periodontal pathogen colonization. | Divaris K et al. | β | 2012 | β |
| Heritability and genome-wide linkage analysis of migraine in the genetic isolate of Norfolk Island. | Cox HC et al. | β | 2012 | β |
| Non-replication of genome-wide-based associations of efficient food conversion in dairy cows. | Littlejohn M et al. | β | 2012 | β |
| Novel associations of nonstructural Loci with paraoxonase activity. | Quillen EE et al. | β | 2012 | β |
| Novel loci associated with PR interval in a genome-wide association study of 10 African American cohorts. | Butler AM et al. | β | 2012 | β |
| QTL and quantitative genetic analysis of beak morphology reveals patterns of standing genetic variation in an Estrildid finch. | Knief U et al. | β | 2012 | β |
| QTL mapping for sexually dimorphic fitness-related traits in wild bighorn sheep. | Poissant J et al. | β | 2012 | β |
| Rare genetic variants and treatment response: sample size and analysis issues. | Witte JS | β | 2012 | β |
| TNFAIP3 gene polymorphisms are associated with response to TNF blockade in psoriasis. | Tejasvi T et al. | β | 2012 | β |
| What paths do advantageous alleles take during short-term evolutionary change? | Burke MK et al. | β | 2012 | β |
| A flexible genome-wide bootstrap method that accounts for ranking and threshold-selection bias in GWAS interpretation and replication study design. | Faye LL et al. | β | 2011 | β |
| A genome-wide metabolic QTL analysis in Europeans implicates two loci shaped by recent positive selection. | Nicholson G et al. | β | 2011 | β |
| BR-squared: a practical solution to the winner's curse in genome-wide scans. | Sun L et al. | β | 2011 | β |
| Cryptic multiple hypotheses testing in linear models: overestimated effect sizes and the winner's curse. | Forstmeier W et al. | β | 2011 | β |
| Genetical genomics of Th1 and Th2 immune response in a baboon model of atherosclerosis risk factors. | Vinson A et al. | β | 2011 | β |
| Genetic analysis of genome-scale recombination rate evolution in house mice. | Dumont BL et al. | β | 2011 | β |
| Genetic association of PICALM polymorphisms with Alzheimer's disease in Han Chinese. | Yu JT et al. | β | 2011 | β |
| Genetic determinants of lipid traits in diverse populations from the population architecture using genomics and epidemiology (PAGE) study. | Dumitrescu L et al. | β | 2011 | β |
| Genome-wide association and linkage identify modifier loci of lung disease severity in cystic fibrosis at 11p13 and 20q13.2. | Wright FA et al. | β | 2011 | β |
| Genome-wide association and meta-analysis in populations from Starr County, Texas, and Mexico City identify type 2 diabetes susceptibility loci and enrichment for expression quantitative trait loci in top signals. | Below JE et al. | β | 2011 | β |
| Genome-wide association studies of chronic kidney disease: what have we learned? | O'Seaghdha CM et al. | β | 2011 | β |
| Genome-wide pharmacogenomic analysis of response to treatment with antipsychotics. | McClay JL et al. | β | 2011 | β |
| Genome-wide pharmacogenomic study of neurocognition as an indicator of antipsychotic treatment response in schizophrenia. | McClay JL et al. | β | 2011 | β |
| Identification, replication, and functional fine-mapping of expression quantitative trait loci in primary human liver tissue. | Innocenti F et al. | β | 2011 | β |
| Linkage and association of phospholipid transfer protein activity to LASS4. | Rosenthal EA et al. | β | 2011 | β |
| Mapping QTLs with main and epistatic effects underlying grain yield and heading time in soft winter wheat. | Reif JC et al. | β | 2011 | β |
| Overview of techniques to account for confounding due to population stratification and cryptic relatedness in genomic data association analyses. | SillanpÀÀ MJ | β | 2011 | β |
| Quantifying and correcting for the winner's curse in quantitative-trait association studies. | Xiao R et al. | β | 2011 | β |
| Statistically significant meta-analyses of clinical trials have modest credibility and inflated effects. | Pereira TV et al. | β | 2011 | β |
| Two-stage study designs combining genome-wide association studies, tag single-nucleotide polymorphisms, and exome sequencing: accuracy of genetic effect estimates. | Faye LL et al. | β | 2011 | β |
| A genome-wide scan for common alleles affecting risk for autism. | Anney R et al. | β | 2010 | β |
| Association mapping of quantitative disease resistance in a natural population of loblolly pine (Pinus taeda L.). | Quesada T et al. | β | 2010 | β |
| Common genetic variants on chromosome 9p21 are associated with myocardial infarction and type 2 diabetes in an Italian population. | Gori F et al. | β | 2010 | β |
| Current status on Alzheimer disease molecular genetics: from past, to present, to future. | Bettens K et al. | β | 2010 | β |
| Estimating effect sizes in genome-wide association studies. | BukszΓ‘r J et al. | β | 2010 | β |
| Gene expression in skin and lymphoblastoid cells: Refined statistical method reveals extensive overlap in cis-eQTL signals. | Ding J et al. | β | 2010 | β |
| Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration. | Chen W et al. | β | 2010 | β |
| Genome-wide association studies: contribution of genomics to understanding blood pressure and essential hypertension. | Ehret GB | β | 2010 | β |
| Genome-wide association study of major recurrent depression in the U.K. population. | Lewis CM et al. | β | 2010 | β |
| Joint QTL analysis of three connected F2-crosses in pigs. | RΓΌckert C et al. | β | 2010 | β |
| Lack of association between PCDH11X genetic variation and late-onset Alzheimer's disease in a Han Chinese population. | Wu ZC et al. | β | 2010 | β |
| PCDH11X variation is not associated with late-onset Alzheimer disease susceptibility. | Beecham GW et al. | β | 2010 | β |
| The end of behavioral genetics? 2008. | McGue M | β | 2010 | β |
| The impact of incomplete linkage disequilibrium and genetic model choice on the analysis and interpretation of genome-wide association studies. | Iles MM | β | 2010 | β |
| Whole genome association analysis shows that ACE is a risk factor for Alzheimer's disease and fails to replicate most candidates from Meta-analysis. | Webster J et al. | β | 2010 | β |
| Bivariate genome-wide linkage analysis of femoral bone traits and leg lean mass: Framingham study. | Karasik D et al. | β | 2009 | β |
| CALHM1 polymorphism is not associated with late-onset Alzheimer disease. | Beecham GW et al. | β | 2009 | β |
| Common genetic variation near the phospholamban gene is associated with cardiac repolarisation: meta-analysis of three genome-wide association studies. | Nolte IM et al. | β | 2009 | β |
| Common regulatory variation impacts gene expression in a cell type-dependent manner. | Dimas AS et al. | β | 2009 | β |
| CTLA4 and generalized vitiligo: two genetic association studies and a meta-analysis of published data. | Birlea SA et al. | β | 2009 | β |
| Determinants of variation in human serum paraoxonase activity. | Rainwater DL et al. | β | 2009 | β |
| Distribution and location of genetic effects for dairy traits. | Cole JB et al. | β | 2009 | β |
| Estimating the posterior probability that genome-wide association findings are true or false. | BukszΓ‘r J et al. | β | 2009 | β |
| Failure to confirm genetic association of the CHI3L1 gene with schizophrenia in Japanese and Chinese populations. | Yamada K et al. | β | 2009 | β |
| Gene association studies in acute lung injury: replication and future direction. | Gong MN | β | 2009 | β |
| Genetic predictors of response to antidepressants in the GENDEP project. | Uher R et al. | β | 2009 | β |
| Genetic studies of amyotrophic lateral sclerosis: controversies and perspectives. | Beleza-Meireles A et al. | β | 2009 | β |
| Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease. | Harold D et al. | β | 2009 | β |
| Human QTL linkage mapping. | Almasy L et al. | β | 2009 | β |
| Quantifying and correcting for the winner's curse in genetic association studies. | Xiao R et al. | β | 2009 | β |
| Ranking bias in association studies. | Jeffries NO | β | 2009 | β |
| Search for quantitative trait loci affecting growth and carcass traits in a cross population of beef and dairy cattle. | GutiΓ©rrez-Gil B et al. | β | 2009 | β |
| Strong evidence for a novel schizophrenia risk locus on chromosome 1p31.1 in homogeneous pedigrees from Tamil Nadu, India. | Holliday EG et al. | β | 2009 | β |
| The genetic aspects of multiple sclerosis. | Sawcer S | β | 2009 | β |
| Unbiased estimation of odds ratios: combining genomewide association scans with replication studies. | Bowden J et al. | β | 2009 | β |
| Accuracy of predicting the genetic risk of disease using a genome-wide approach. | Daetwyler HD et al. | β | 2008 | β |
| A genome scan to detect quantitative trait loci for economically important traits in Holstein cattle using two methods and a dense single nucleotide polymorphism map. | Daetwyler HD et al. | β | 2008 | β |
| A genomewide linkage scan for quantitative trait loci influencing the craniofacial complex in baboons (Papio hamadryas spp.). | Sherwood RJ et al. | β | 2008 | β |
| A genome wide linkage scan of metacarpal size and geometry in the Framingham Study. | Karasik D et al. | β | 2008 | β |
| Analysis of quantitative trait loci. | Falchi M | β | 2008 | β |
| Association between the interleukin-1beta polymorphisms and Alzheimer's disease: a systematic review and meta-analysis. | Di Bona D et al. | β | 2008 | β |
| Candidate gene polymorphisms and the 9p21 locus in acute coronary syndromes. | Tousoulis D et al. | β | 2008 | β |
| Controlling false discoveries in genetic studies. | van den Oord EJ | β | 2008 | β |
| Design and analysis of genetic association studies to finely map a locus identified by linkage analysis: assessment of the extent to which an association can account for the linkage. | Hanson RL et al. | β | 2008 | β |
| Estimating odds ratios in genome scans: an approximate conditional likelihood approach. | Ghosh A et al. | β | 2008 | β |
| Forum: Interactions between gene and environment. | Flint J et al. | β | 2008 | β |
| Genome-wide association scan identifies a prostaglandin-endoperoxide synthase 2 variant involved in risk of knee osteoarthritis. | Valdes AM et al. | β | 2008 | β |
| Genome-wide association studies: potential next steps on a genetic journey. | McCarthy MI et al. | β | 2008 | β |
| Genome-wide association studies: progress and potential for drug discovery and development. | Kingsmore SF et al. | β | 2008 | β |
| Genome-wide linkage analyses of quantitative and categorical autism subphenotypes. | Liu XQ et al. | β | 2008 | β |
| Genome-wide linkage analysis of multiple measures of neuroticism of 2 large cohorts from Australia and the Netherlands. | Wray NR et al. | β | 2008 | β |
| Genotype-specific recurrence risks as indicators of the genetic architecture of complex diseases. | Slatkin M | β | 2008 | β |
| Identification and replication of a novel obesity locus on chromosome 1q24 in isolated populations of Cilento. | Ciullo M et al. | β | 2008 | β |
| Identification of LTBP2 on chromosome 14q as a novel candidate gene for bone mineral density variation and fracture risk association. | Cheung CL et al. | β | 2008 | β |
| Impact of nine common type 2 diabetes risk polymorphisms in Asian Indian Sikhs: PPARG2 (Pro12Ala), IGF2BP2, TCF7L2 and FTO variants confer a significant risk. | Sanghera DK et al. | β | 2008 | β |
| Is replication the gold standard for validating genome-wide association findings? | Liu YJ et al. | β | 2008 | β |
| Mapping interspecific genetic architecture in a host-parasite interaction system. | Yang J et al. | β | 2008 | β |
| Meta-analysis methods. | Trikalinos TA et al. | β | 2008 | β |
| Multiple superoxide dismutase 1/splicing factor serine alanine 15 variants are associated with the development and progression of diabetic nephropathy: the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Genetics study. | Al-Kateb H et al. | β | 2008 | β |
| Nucleotide polymorphism and phenotypic associations within and around the phytochrome B2 Locus in European aspen (Populus tremula, Salicaceae). | Ingvarsson PK et al. | β | 2008 | β |
| Pharmacogenetics of major depression: insights from level 1 of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. | Lekman M et al. | β | 2008 | β |
| TCF7L2 polymorphisms are associated with type 2 diabetes in Khatri Sikhs from North India: genetic variation affects lipid levels. | Sanghera DK et al. | β | 2008 | β |
| The complex genetics of multiple sclerosis: pitfalls and prospects. | Sawcer S | β | 2008 | β |
| The End of Behavioral Genetics? | McGue M | β | 2008 | β |
| Tilting at quixotic trait loci (QTL): an evolutionary perspective on genetic causation. | Weiss KM | β | 2008 | β |
| What can genome-wide association studies tell us about the genetics of common disease? | Iles MM | β | 2008 | β |
| Why most discovered true associations are inflated. | Ioannidis JP | β | 2008 | β |
| Bivariate linkage study of proximal hip geometry and body size indices: the Framingham study. | Karasik D et al. | β | 2007 | β |
| Confidence intervals for putative quantitative trait loci - development and applications of new linkage methods. | Papachristou C et al. | β | 2007 | β |
| Discovery of expression QTLs using large-scale transcriptional profiling in human lymphocytes. | GΓΆring HH et al. | β | 2007 | β |
| Estimating the number and size of the main effects in genome-wide case-control association studies. | Kuo PH et al. | β | 2007 | β |
| Evidence for linkage of red blood cell size and count: genome-wide scans in the Framingham Heart Study. | Lin JP et al. | β | 2007 | β |
| Flexible design for following up positive findings. | Yu K et al. | β | 2007 | β |
| Genome-wide association studies: progress in identifying genetic biomarkers in common, complex diseases. | Kingsmore SF et al. | β | 2007 | β |
| Mapping quantitative trait Loci underlying fitness-related traits in a free-living sheep population. | Beraldi D et al. | β | 2007 | β |
| Meta analysis of whole-genome linkage scans with data uncertainty: an application to Parkinson's disease. | Rosenberger A et al. | β | 2007 | β |
| MOD-score analysis with simple pedigrees: an overview of likelihood-based linkage methods. | Strauch K | β | 2007 | β |
| Molecular evidence-based medicine: evolution and integration of information in the genomic era. | Ioannidis JP | β | 2007 | β |
| Multiple genes for essential-hypertension susceptibility on chromosome 1q. | Chang YP et al. | β | 2007 | β |
| Non-replication of association studies: "pseudo-failures" to replicate? | Gorroochurn P et al. | β | 2007 | β |
| Optimal selection of markers for validation or replication from genome-wide association studies. | Greenwood CM et al. | β | 2007 | β |
| Overcoming the winner's curse: estimating penetrance parameters from case-control data. | Zollner S et al. | β | 2007 | β |
| Proximal hip geometry is linked to several chromosomal regions: genome-wide linkage results from the Framingham Osteoporosis Study. | Demissie S et al. | β | 2007 | β |
| Residual linkage: why do linkage peaks not disappear after an association study? | Gordon S et al. | β | 2007 | β |
| Robust multipoint simultaneous identical-by-descent mapping for two linked loci. | Lin WY et al. | β | 2007 | β |
| Strong evidence of a genetic determinant for mammographic density, a major risk factor for breast cancer. | Vachon CM et al. | β | 2007 | β |
| Upward bias in odds ratio estimates from genome-wide association studies. | Garner C | β | 2007 | β |
| A genome scan for epidermal skin pattern in adolescent twins reveals suggestive linkage on 12p13.31. | Shekar SN et al. | β | 2006 | β |
| A simple method to localise pleiotropic susceptibility loci using univariate linkage analyses of correlated traits. | Ferreira MA et al. | β | 2006 | β |
| Association analysis of the chromosome 4p-located G protein-coupled receptor 78 (GPR78) gene in bipolar affective disorder and schizophrenia. | Underwood SL et al. | β | 2006 | β |
| Dissecting complex disease: the quest for the Philosopher's Stone? | Buchanan AV et al. | β | 2006 | β |
| Evidence for involvement of the vitamin D receptor gene in idiopathic short stature via a genome-wide linkage study and subsequent association studies. | Dempfle A et al. | β | 2006 | β |
| Gene mapping strategies for complex disease and drug response. | Jawaid A et al. | β | 2006 | β |
| Genome-wide linkage scan to identify Loci for age at first cigarette in Dutch sibling pairs. | Vink JM et al. | β | 2006 | β |
| Genome-wide mapping of susceptibility to coronary artery disease identifies a novel replicated locus on chromosome 17. | Farrall M et al. | β | 2006 | β |
| Genome-wide scan identified QTLs underlying femoral neck cross-sectional geometry that are novel studied risk factors of osteoporosis. | Xiong DH et al. | β | 2006 | β |
| Identification of quantitative trait loci that regulate Arabidopsis root system size and plasticity. | Fitz Gerald JN et al. | β | 2006 | β |
| Increased support for linkage of a novel locus on chromosome 5q13 for essential hypertension in the British Genetics of Hypertension Study. | Munroe PB et al. | β | 2006 | β |
| Interval mapping of quantitative trait loci for time-to-event data with the proportional hazards mixture cure model. | Liu M et al. | β | 2006 | β |
| Locus-specific heritability estimation via the bootstrap in linkage scans for quantitative trait loci. | Wu LY et al. | β | 2006 | β |
| Mapping genetic loci that determine leukocyte telomere length in a large sample of unselected female sibling pairs. | Andrew T et al. | β | 2006 | β |
| Murine weight loss exhibits significant genetic variation during dietary restriction. | Rikke BA et al. | β | 2006 | β |
| Osteoarthritis susceptibility loci defined by genome scan meta-analysis. | Lee YH et al. | β | 2006 | β |
| Osteoarthritis susceptibility loci defined by genome scan meta-analysis. | Lee YH et al. | β | 2006 | β |
| PowQ: a user-friendly package for the design of variance component multipoint linkage analysis studies. | Falchi M et al. | β | 2006 | β |
| QTL analysis of intraspecific differences between two Silene vulgaris ecotypes. | Bratteler M et al. | β | 2006 | β |
| Replication of small effect quantitative trait loci for behavioral traits facilitated by estimation of effect size from independent cohorts. | Bennett B et al. | β | 2006 | β |
| Sex and age specific effects of chromosomal regions linked to body mass index in the Framingham Study. | Atwood LD et al. | β | 2006 | β |
| Testing of variants of the MTHFR and ESR1 genes in 1798 Finnish individuals fails to confirm the association with migraine with aura. | Kaunisto MA et al. | β | 2006 | β |
| The genetics of autism spectrum disorders. | Grice DE et al. | β | 2006 | β |
| The use of random controls in genetic association studies. | Garner C | β | 2006 | β |
| Towards compendia of negative genetic association studies: an example for Alzheimer disease. | Blomqvist ME et al. | β | 2006 | β |
| Ankylosing spondylitis susceptibility loci defined by genome-search meta-analysis. | Lee YH et al. | β | 2005 | β |
| A whole-genome scan for 24-hour respiration rate: a major locus at 10q26 influences respiration during sleep. | de Geus EJ et al. | β | 2005 | β |
| Biased estimators of quantitative trait locus heritability and location in interval mapping. | Bogdan M et al. | β | 2005 | β |
| Effect of population size on the estimation of QTL: a test using resistance to barley stripe rust. | Vales MI et al. | β | 2005 | β |
| Gearing up for genome-wide gene-association studies. | Farrall M et al. | β | 2005 | β |
| Gene symbol: MPZ. Disease: Charcot-Marie-Tooth disease type 1B. | Lee YC et al. | β | 2005 | β |
| Genetic association studies in stroke: methodological issues and proposed standard criteria. | Dichgans M et al. | β | 2005 | β |
| Genetic epidemiology and public health: hope, hype, and future prospects. | Davey Smith G et al. | β | 2005 | β |
| Genetics and coronary heart disease. | Cambien F | β | 2005 | β |
| Genetics of Type 2 diabetes. | Barroso I | β | 2005 | β |
| Genetic studies of osteoporosis--a rethink required. | Brown MA | β | 2005 | β |
| Genome scan of systemic biomarkers of vascular inflammation in the Framingham Heart Study: evidence for susceptibility loci on 1q. | Dupuis J et al. | β | 2005 | β |
| Genomewide linkage study in 1,176 affected sister pair families identifies a significant susceptibility locus for endometriosis on chromosome 10q26. | Treloar SA et al. | β | 2005 | β |
| Genome-wide scans for loci under selection in humans. | Ronald J et al. | β | 2005 | β |
| High factor VIII levels in venous thromboembolism show linkage to imprinted loci on chromosomes 5 and 11. | Berger M et al. | β | 2005 | β |
| Identification of QTLs for serum lipid levels in a female sib-pair cohort: a novel application to improve the power of two-locus linkage analysis. | Falchi M et al. | β | 2005 | β |
| Linkage analysis of anorexia and bulimia nervosa cohorts using selected behavioral phenotypes as quantitative traits or covariates. | Bacanu SA et al. | β | 2005 | β |
| Macrophage scavenger receptor 1 999C>T (R293X) mutation and risk of prostate cancer. | Hope Q et al. | β | 2005 | β |
| Mapping of quantitative trait loci affecting organ weights and blood variables in a broiler layer cross. | Navarro P et al. | β | 2005 | β |
| Mapping quantitative trait loci for cross-sectional geometry at the femoral neck. | Shen H et al. | β | 2005 | β |
| Multiple QTLs influencing triglyceride and HDL and total cholesterol levels identified in families with atherogenic dyslipidemia. | Yu Y et al. | β | 2005 | β |
| Nonreplication in genetic studies of complex diseases--lessons learned from studies of osteoporosis and tentative remedies. | Shen H et al. | β | 2005 | β |
| Quantitative founder-effect analysis of French Canadian families identifies specific loci contributing to metabolic phenotypes of hypertension. | Hamet P et al. | β | 2005 | β |
| Reduction of selection bias in genomewide studies by resampling. | Sun L et al. | β | 2005 | β |
| Relationships between familial risks of cancer and the effects of heritable genes and their SNP variants. | Hemminki K et al. | β | 2005 | β |
| Resampling methods to reduce the selection bias in genetic effect estimation in genome-wide scans. | Wu LY et al. | β | 2005 | β |
| Robust estimation of experimentwise P values applied to a genome scan of multiple asthma traits identifies a new region of significant linkage on chromosome 20q13. | Ferreira MA et al. | β | 2005 | β |
| Robust multipoint identical-by-descent mapping for affected relative pairs. | Schaid DJ et al. | β | 2005 | β |
| Shaking the tree: mapping complex disease genes with linkage disequilibrium. | Palmer LJ et al. | β | 2005 | β |
| Statistical tools for linkage analysis and genetic association studies. | Forabosco P et al. | β | 2005 | β |
| Strong association of the Y402H variant in complement factor H at 1q32 with susceptibility to age-related macular degeneration. | Zareparsi S et al. | β | 2005 | β |
| Systemic lupus erythematosus susceptibility loci defined by genome scan meta-analysis. | Lee YH et al. | β | 2005 | β |
| Theoretical models of selection and mutation on quantitative traits. | Johnson T et al. | β | 2005 | β |
| The role of a common adenosine monophosphate deaminase (AMPD)-1 polymorphism in outcomes of ischemic and nonischemic heart failure. | Kolek MJ et al. | β | 2005 | β |
| Three autism candidate genes: a synthesis of human genetic analysis with other disciplines. | Bartlett CW et al. | β | 2005 | β |
| A large-sample QTL study in mice: I. Growth. | Rocha JL et al. | β | 2004 | β |
| Association of genetic loci: replication or not, that is the question. | Ott J | β | 2004 | β |
| Confirmation of chromosome 7q11 locus for predisposition to intracranial aneurysm. | Farnham JM et al. | β | 2004 | β |
| Effect of winsorization on power and type 1 error of variance components and related methods of QTL detection. | Shete S et al. | β | 2004 | β |
| Establishment of genetic associations for complex diseases is independent of early study findings. | Trikalinos TA et al. | β | 2004 | β |
| Exploring positional candidate genes: linkage conditional on measured genotype. | Almasy L et al. | β | 2004 | β |
| Gamma regression improves Haseman-Elston and variance components linkage analysis for sib-pairs. | Barber MJ et al. | β | 2004 | β |
| Genetic dissection of human stature in a large sample of multiplex pedigrees. | Liu YZ et al. | β | 2004 | β |
| Genome-wide linkage to chromosome 6 for waist circumference in the Framingham Heart Study. | Fox CS et al. | β | 2004 | β |
| Genome-wide scan for blood pressure suggests linkage to chromosome 11, and replication of loci on 16, 17, and 22. | de Lange M et al. | β | 2004 | β |
| Investigation of susceptibility loci identified in the UK rheumatoid arthritis whole-genome scan in a further series of 217 UK affected sibling pairs. | Eyre S et al. | β | 2004 | β |
| Linkage analysis of extremely discordant and concordant sibling pairs identifies quantitative trait loci influencing variation in human menopausal age. | van Asselt KM et al. | β | 2004 | β |
| Multicenter linkage study of schizophrenia loci on chromosome 22q. | Mowry BJ et al. | β | 2004 | β |
| Multiple quantitative trait loci mapping with cofactors and application of alternative variants of the false discovery rate in an enlarged granddaughter design. | Bennewitz J et al. | β | 2004 | β |
| Power of variance component linkage analysis-II. Discrete traits. | Williams JT et al. | β | 2004 | β |
| Quantitative trait locus determining dietary macronutrient intakes is located on human chromosome 2p22. | Cai G et al. | β | 2004 | β |
| Quantitative trait locus mapping based on resampling in a vast maize testcross experiment and its relevance to quantitative genetics for complex traits. | SchΓΆn CC et al. | β | 2004 | β |
| Replication of 1q42 linkage in Finnish schizophrenia pedigrees. | Ekelund J et al. | β | 2004 | β |
| The common variants/multiple disease hypothesis of common complex genetic disorders. | Becker KG | β | 2004 | β |
| The molecular genetics of schizophrenia: new findings promise new insights. | Owen MJ et al. | β | 2004 | β |
| The thyroglobulin gene: the third locus for autoimmune thyroid disease or a false dawn? | Gough S | β | 2004 | β |
| A major susceptibility locus on chromosome 22q12 plays a critical role in the control of kala-azar. | Bucheton B et al. | β | 2003 | β |
| A quantitative trait locus on chromosome 16q influences variation in plasma HDL-C levels in Mexican Americans. | Mahaney MC et al. | β | 2003 | β |
| Assessing accuracy in linkage analysis by means of confidence regions. | HΓΆssjer O | β | 2003 | β |
| Association mapping of complex diseases in linked regions: estimation of genetic effects and feasibility of testing rare variants. | Wang WY et al. | β | 2003 | β |
| A systematic genomewide linkage study in 353 sib pairs with schizophrenia. | Williams NM et al. | β | 2003 | β |
| Bayesian analysis of multilocus association in quantitative and qualitative traits. | Kilpikari R et al. | β | 2003 | β |
| Estimating polygenic effects using markers of the entire genome. | Xu S | β | 2003 | β |
| Genetic associations in large versus small studies: an empirical assessment. | Ioannidis JP et al. | β | 2003 | β |
| Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: Schizophrenia. | Lewis CM et al. | β | 2003 | β |
| Genome scan meta-analysis of schizophrenia and bipolar disorder, part I: Methods and power analysis. | Levinson DF et al. | β | 2003 | β |
| Genome-wide linkage analysis of serum adiponectin in the Pima Indian population. | Lindsay RS et al. | β | 2003 | β |
| Growing evidence for diabetes susceptibility genes from genome scan data. | McCarthy MI | β | 2003 | β |
| Insurance companies' access to genetic information: why regulation alone is not enough. | Juth N | β | 2003 | β |
| Limits of fine-mapping a quantitative trait. | Atwood LD et al. | β | 2003 | β |
| Linkage analysis of quantitative trait loci in the presence of heterogeneity. | EkstrΓΈm CT et al. | β | 2003 | β |
| Linkage for BMI at 3q27 region confirmed in an African-American population. | Luke A et al. | β | 2003 | β |
| Linkage of osteoporosis to chromosome 20p12 and association to BMP2. | Styrkarsdottir U et al. | β | 2003 | β |
| Mapping determinants of variation in energy metabolism, respiration and flight in Drosophila. | Montooth KL et al. | β | 2003 | β |
| Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease. | Lohmueller KE et al. | β | 2003 | β |
| Multipoint affected sibpair linkage methods for localizing susceptibility genes of complex diseases. | Glidden DV et al. | β | 2003 | β |
| Natural selection for salt tolerance quantitative trait loci (QTLs) in wild sunflower hybrids: implications for the origin of Helianthus paradoxus, a diploid hybrid species. | Lexer C et al. | β | 2003 | β |
| Polymorphisms at the G72/G30 gene locus, on 13q33, are associated with bipolar disorder in two independent pedigree series. | Hattori E et al. | β | 2003 | β |
| Population stratification and spurious allelic association. | Cardon LR et al. | β | 2003 | β |
| Problems of reporting genetic associations with complex outcomes. | Colhoun HM et al. | β | 2003 | β |
| Recent advances in the genetics of schizophrenia. | O'Donovan MC et al. | β | 2003 | β |
| Several genomic regions potentially containing QTLs for bone size variation were identified in a whole-genome linkage scan. | Deng HW et al. | β | 2003 | β |
| Sum statistics for the joint detection of multiple disease loci in case-control association studies with SNP markers. | Wille A et al. | β | 2003 | β |
| The twofold difference in adult size between the red junglefowl and White Leghorn chickens is largely explained by a limited number of QTLs. | Kerje S et al. | β | 2003 | β |
| A genomewide linkage scan for quantitative-trait loci for obesity phenotypes. | Deng HW et al. | β | 2002 | β |
| A genomewide linkage screen for relative hand skill in sibling pairs. | Francks C et al. | β | 2002 | β |
| A genome-wide scan for linkage to chromosomal regions in 382 sibling pairs with schizophrenia or schizoaffective disorder. | DeLisi LE et al. | β | 2002 | β |
| A quantitative trait locus on chromosome 22 for serum leptin levels adjusted for serum testosterone. | Martin LJ et al. | β | 2002 | β |
| A susceptibility gene for late-onset idiopathic Parkinson's disease. | Hicks AA et al. | β | 2002 | β |
| Attributable risks for familial breast cancer by proband status and morphology: a nationwide epidemiologic study from Sweden. | Hemminki K et al. | β | 2002 | β |
| A whole-genome linkage scan suggests several genomic regions potentially containing QTLs underlying the variation of stature. | Deng HW et al. | β | 2002 | β |
| A whole-genome linkage scan suggests several genomic regions potentially containing quantitative trait Loci for osteoporosis. | Deng HW et al. | β | 2002 | β |
| Bias in estimates of quantitative-trait-locus effect in genome scans: demonstration of the phenomenon and a method-of-moments procedure for reducing bias. | Allison DB et al. | β | 2002 | β |
| Developmental dyslexia: genetic dissection of a complex cognitive trait. | Fisher SE et al. | β | 2002 | β |
| Evidence for linkage of stature to chromosome 3p26 in a large U.K. Family data set ascertained for type 2 diabetes. | Wiltshire S et al. | β | 2002 | β |
| Genomewide linkage analysis of body mass index across 28 years of the Framingham Heart Study. | Atwood LD et al. | β | 2002 | β |
| Heritability of subclinical atherosclerosis in Latino families ascertained through a hypertensive parent. | Xiang AH et al. | β | 2002 | β |
| Interpretation of genetic association studies in complex disease. | Campbell H et al. | β | 2002 | β |
| Mapping and analysis of quantitative trait loci in experimental populations. | Doerge RW | β | 2002 | β |
| Neuregulin 1 and susceptibility to schizophrenia. | Stefansson H et al. | β | 2002 | β |
| No major schizophrenia locus detected on chromosome 1q in a large multicenter sample. | Levinson DF et al. | β | 2002 | β |
| Parameters for reliable results in genetic association studies in common disease. | Dahlman I et al. | β | 2002 | β |
| The application of genetics to the discovery of better medicines. | Pettipher R et al. | β | 2002 | β |
| The changing face of epidemiology in the genomics era. | Millikan R | β | 2002 | β |
| The genetic basis of dyslexia. | Francks C et al. | β | 2002 | β |
| Upward bias in estimation of genetic effects. | Siegmund D | β | 2002 | β |