Hundreds of variants clustered in genomic loci and biological pathways affect human height.
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- Lango Allen, Hana; Estrada, Karol; Lettre, Guillaume; Berndt, Sonja I; Weedon, Michael N; Rivadeneira, Fernando; Willer, Cristen J; Jackson, Anne U; Vedantam, Sailaja; Raychaudhuri, Soumya; Ferreira, Teresa; Wood, Andrew R; Weyant, Robert J; SegrΓ¨, Ayellet V; Speliotes, Elizabeth K; Wheeler, Eleanor; Soranzo, Nicole; Park, Ju-Hyun; Yang, Jian; Gudbjartsson, Daniel; Heard-Costa, Nancy L; Randall, Joshua C; Qi, Lu; Vernon Smith, Albert; MΓ€gi, Reedik; Pastinen, Tomi; Liang, Liming; Heid, Iris M; Luan, Jian'an; Thorleifsson, Gudmar; Winkler, Thomas W; Goddard, Michael E; Sin Lo, Ken; Palmer, Cameron; Workalemahu, Tsegaselassie; Aulchenko, Yurii S; Johansson, Asa; Zillikens, M Carola; Feitosa, Mary F; Esko, TΓ΅nu; Johnson, Toby; Ketkar, Shamika; Kraft, Peter; Mangino, Massimo; Prokopenko, Inga; Absher, Devin; Albrecht, Eva; Ernst, Florian; Glazer, Nicole L; Hayward, Caroline; Hottenga, Jouke-Jan; Jacobs, Kevin B; Knowles, Joshua W; Kutalik, ZoltΓ‘n; Monda, Keri L; Polasek, Ozren; Preuss, Michael; Rayner, Nigel W; Robertson, Neil R; Steinthorsdottir, Valgerdur; Tyrer, Jonathan P; Voight, Benjamin F; Wiklund, Fredrik; Xu, Jianfeng; Zhao, Jing Hua; Nyholt, Dale R; Pellikka, Niina; Perola, Markus; Perry, John R B; Surakka, Ida; Tammesoo, Mari-Liis; Altmaier, Elizabeth L; Amin, Najaf; Aspelund, Thor; Bhangale, Tushar; Boucher, Gabrielle; Chasman, Daniel I; Chen, Constance; Coin, Lachlan; Cooper, Matthew N; Dixon, Anna L; Gibson, Quince; Grundberg, Elin; Hao, Ke; Juhani Junttila, M; Kaplan, Lee M; Kettunen, Johannes; KΓΆnig, Inke R; Kwan, Tony; Lawrence, Robert W; Levinson, Douglas F; Lorentzon, Mattias; McKnight, Barbara; Morris, Andrew P; MΓΌller, Martina; Suh Ngwa, Julius; Purcell, Shaun; Rafelt, Suzanne; Salem, Rany M; Salvi, Erika; Sanna, Serena; Shi, Jianxin; Sovio, Ulla; Thompson, John R; Turchin, Michael C; Vandenput, Liesbeth; Verlaan, Dominique J; Vitart, Veronique; White, Charles C; Ziegler, Andreas; Almgren, Peter; Balmforth, Anthony J; Campbell, Harry; Citterio, Lorena; De Grandi, Alessandro; Dominiczak, Anna; Duan, Jubao; Elliott, Paul; Elosua, Roberto; Eriksson, Johan G; Freimer, Nelson B; Geus, Eco J C; Glorioso, Nicola; Haiqing, Shen; Hartikainen, Anna-Liisa; Havulinna, Aki S; Hicks, Andrew A; Hui, Jennie; Igl, Wilmar; Illig, Thomas; Jula, Antti; Kajantie, Eero; KilpelΓ€inen, Tuomas O; Koiranen, Markku; Kolcic, Ivana; Koskinen, Seppo; Kovacs, Peter; Laitinen, Jaana; Liu, Jianjun; Lokki, Marja-Liisa; Marusic, Ana; Maschio, Andrea; Meitinger, Thomas; Mulas, Antonella; ParΓ©, Guillaume; Parker, Alex N; Peden, John F; Petersmann, Astrid; Pichler, Irene; PietilΓ€inen, Kirsi H; Pouta, Anneli; RidderstrΓ₯le, Martin; Rotter, Jerome I; Sambrook, Jennifer G; Sanders, Alan R; Schmidt, Carsten Oliver; Sinisalo, Juha; Smit, Jan H; Stringham, Heather M; Bragi Walters, G; Widen, Elisabeth; Wild, Sarah H; Willemsen, Gonneke; Zagato, Laura; Zgaga, Lina; Zitting, Paavo; Alavere, Helene; Farrall, Martin; McArdle, Wendy L; Nelis, Mari; Peters, Marjolein J; Ripatti, Samuli; van Meurs, Joyce B J; Aben, Katja K; Ardlie, Kristin G; Beckmann, Jacques S; Beilby, John P; Bergman, Richard N; Bergmann, Sven; Collins, Francis S; Cusi, Daniele; den Heijer, Martin; Eiriksdottir, Gudny; Gejman, Pablo V; Hall, Alistair S; Hamsten, Anders; Huikuri, Heikki V; Iribarren, Carlos; KΓ€hΓΆnen, Mika; Kaprio, Jaakko; Kathiresan, Sekar; Kiemeney, Lambertus; Kocher, Thomas; Launer, Lenore J; LehtimΓ€ki, Terho; Melander, Olle; Mosley, Tom H; Musk, Arthur W; Nieminen, Markku S; O'Donnell, Christopher J; Ohlsson, Claes; Oostra, Ben; Palmer, Lyle J; Raitakari, Olli; Ridker, Paul M; Rioux, John D; Rissanen, Aila; Rivolta, Carlo; Schunkert, Heribert; Shuldiner, Alan R; Siscovick, David S; Stumvoll, Michael; TΓΆnjes, Anke; Tuomilehto, Jaakko; van Ommen, Gert-Jan; Viikari, Jorma; Heath, Andrew C; Martin, Nicholas G; Montgomery, Grant W; Province, Michael A; Kayser, Manfred; Arnold, Alice M; Atwood, Larry D; Boerwinkle, Eric; Chanock, Stephen J; Deloukas, Panos; Gieger, Christian; GrΓΆnberg, Henrik; Hall, Per; Hattersley, Andrew T; Hengstenberg, Christian; Hoffman, Wolfgang; Lathrop, G Mark; Salomaa, Veikko; Schreiber, Stefan; Uda, Manuela; Waterworth, Dawn; Wright, Alan F; Assimes, Themistocles L; Barroso, InΓͺs; Hofman, Albert; Mohlke, Karen L; Boomsma, Dorret I; Caulfield, Mark J; Cupples, L Adrienne; Erdmann, Jeanette; Fox, Caroline S; Gudnason, Vilmundur; Gyllensten, Ulf; Harris, Tamara B; Hayes, Richard B; Jarvelin, Marjo-Riitta; Mooser, Vincent; Munroe, Patricia B; Ouwehand, Willem H; Penninx, Brenda W; Pramstaller, Peter P; Quertermous, Thomas; Rudan, Igor; Samani, Nilesh J; Spector, Timothy D; VΓΆlzke, Henry; Watkins, Hugh; Wilson, James F; Groop, Leif C; Haritunians, Talin; Hu, Frank B; Kaplan, Robert C; Metspalu, Andres; North, Kari E; Schlessinger, David; Wareham, Nicholas J; Hunter, David J; O'Connell, Jeffrey R; Strachan, David P; Wichmann, H-Erich; Borecki, Ingrid B; van Duijn, Cornelia M; Schadt, Eric E; Thorsteinsdottir, Unnur; Peltonen, Leena; Uitterlinden, AndrΓ© G; Visscher, Peter M; Chatterjee, Nilanjan; Loos, Ruth J F; Boehnke, Michael; McCarthy, Mark I; Ingelsson, Erik; Lindgren, Cecilia M; Abecasis, GonΓ§alo R; Stefansson, Kari; Frayling, Timothy M; Hirschhorn, Joel N
- Year
- 2010
- Journal
- Nature
- PMID
- 20881960
- DOI
- 10.1038/nature09410
- PMCID
- PMC2955183
Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (Pβ<β0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
Phenotypic variance explained by common variants(a) Variance explained is higher when SNPs not reaching genome-wide significance are included in the prediction model. The y-axis represents the proportion of variance explained at different P-value thresholds from Stage 1. Results are given for five studies that were not part of Stage 1. *Proportion of variation explained by the 180 SNPs. (b) Cumulative number of susceptibility loci expected to be discovered, including already identified loci and as yet undetected loci. The projections are based on loci that achieved a significance level of P<5Γ10-8 in the initial scan and the distribution of their effect sizes in Stage 2. The dotted red line corresponds to expected phenotypic variance explained by the 110 loci that reached genome-wide significance in Stage 1, were replicated in Stage 2 and had at least 1% power.
Example of a locus with a secondary signal before (a) and after (b) conditioningThe plot is centered on the conditioned SNP (purple diamond) at the locus. r2 is based on the CEU HapMap II samples. The blue line and right hand Y axis represent CEU HapMap II recombination rates. Created using LocusZoom (http://csg.sph.umich.edu/locuszoom/).
Loci associated with height contain genes related to each other(a) 180 height-associated SNPs. The y-axis plots GRAIL P-values on a log scale. The histogram corresponds to the distribution of GRAIL P-values for 1,000 sets of 180 matched SNPs. The scatter plot represents GRAIL results for the 180 height SNPs (blue dots). The black horizontal line marks the median of the GRAIL P-values (P=0.14). The top 10 keywords linking the genes were: βgrowthβ, βkinaseβ, βfactorβ, βtranscriptionβ, βsignalingβ, βbindingβ, βdifferentiationβ, βdevelopmentβ, βinsulinβ, βboneβ. (b) Graphical representation of the connections between SNPs and corresponding genes for the 42 SNPs with GRAIL P<0.01. Thicker and redder lines imply stronger literature-based connectivity.
| # | Section | Preview |
|---|---|---|
| 0 | Methods summary | The primary meta-analysis (Stage 1) included 46 GWA studies of 133,653 individuals. The in-silico⦠|
| 1 | Methods summary | and traits to determine the test statistic30. We used a previously described method to estimate the⦠|
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| PLAG1 and NCAPG-LCORL in livestock. | Takasuga A | β | 2016 | β |
| Pleiotropic Genes Affecting Carcass Traits in Bos indicus (Nellore) Cattle Are Modulators of Growth. | G T Pereira A et al. | β | 2016 | β |
| Power considerations for Ξ» inflation factor in meta-analyses of genome-wide association studies. | Georgiopoulos G et al. | β | 2016 | β |
| Primordial dwarfism: overview of clinical and genetic aspects. | Khetarpal P et al. | β | 2016 | β |
| Selection signatures in Shetland ponies. | Frischknecht M et al. | β | 2016 | β |
| Skeletal variation in Tennessee Walking Horses maps to the LCORL/NCAPG gene region. | Staiger EA et al. | β | 2016 | β |
| Sparse meta-analysis with high-dimensional data. | He Q et al. | β | 2016 | β |
| The genetic burden of inflammatory bowel diseases: implications for the clinic? | Gabbani T et al. | β | 2016 | β |
| The genetics of drug efficacy: opportunities and challenges. | Nelson MR et al. | β | 2016 | β |
| The Hippo signal transduction network for exercise physiologists. | Gabriel BM et al. | β | 2016 | β |
| The Relevance of Genomic Signatures at Adhesion GPCR Loci in Humans. | Kovacs P et al. | β | 2016 | β |
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| UGT2B4 previously implicated in the risk of breast cancer is associated with menarche timing in Ukrainian females. | Yermachenko A et al. | β | 2016 | β |
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| Variations in the high-mobility group-A2 gene (HMGA2) are associated with idiopathic short stature. | Fusco I et al. | β | 2016 | β |
| Vitamin D receptor polymorphisms and growth until adulthood after very premature birth. | Finken MJ et al. | β | 2016 | β |
| Weighted Genetic Risk Scores and Prediction of Weight Gain in Solid Organ Transplant Populations. | Saigi-Morgui N et al. | β | 2016 | β |
| What accounts for ethnic differences in newborn skinfold thickness comparing South Asians and White Caucasians? Findings from the START and FAMILY Birth Cohorts. | Anand SS et al. | β | 2016 | β |
| Which Genetics Variants in DNase-Seq Footprints Are More Likely to Alter Binding? | Moyerbrailean GA et al. | β | 2016 | β |
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| Why internal weights should be avoided (not only) in MR-Egger regression. | Hartwig FP et al. | β | 2016 | β |
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| Advances in Skeletal Dysplasia Genetics. | Geister KA et al. | β | 2015 | β |
| A Genome-Wide Association Study Identifies the Skin Color Genes IRF4, MC1R, ASIP, and BNC2 Influencing Facial Pigmented Spots. | Jacobs LC et al. | β | 2015 | β |
| A GWAS assessment of the contribution of genomic imprinting to the variation of body mass index in mice. | Hu Y et al. | β | 2015 | β |
| Alcohol Dependence Genetics: Lessons Learned From Genome-Wide Association Studies (GWAS) and Post-GWAS Analyses. | Hart AB et al. | β | 2015 | β |
| Allelic variation, aneuploidy, and nongenetic mechanisms suppress a monogenic trait in yeast. | Sirr A et al. | β | 2015 | β |
| A meta analysis of genome-wide association studies for limb bone lengths in four pig populations. | Guo Y et al. | β | 2015 | β |
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| A PAX1 enhancer locus is associated with susceptibility to idiopathic scoliosis in females. | Sharma S et al. | β | 2015 | β |
| APLP2 Regulates Refractive Error and Myopia Development in Mice and Humans. | Tkatchenko AV et al. | β | 2015 | β |
| Application of high-dimensional feature selection: evaluation for genomic prediction in man. | Bermingham ML et al. | β | 2015 | β |
| Assessing the Causal Relationship of Maternal Height on Birth Size and Gestational Age at Birth: A Mendelian Randomization Analysis. | Zhang G et al. | β | 2015 | β |
| Association of PCK1 with Body Mass Index and Other Metabolic Features in Patients With Psychotropic Treatments. | Saigi-Morgui N et al. | β | 2015 | β |
| Association Study of GWAS-Derived Loci with Height in Brazilian Children: Importance of MAP3K3, MMP24 and IGF1R Polymorphisms for Height Variation. | Fontenele EG et al. | β | 2015 | β |
| A systems genetics study of swine illustrates mechanisms underlying human phenotypic traits. | Zhu J et al. | β | 2015 | β |
| Between Scylla and Charybdis: renegotiating resolution of the 'obstetric dilemma' in response to ecological change. | Wells JC | β | 2015 | β |
| Biological interpretation of genome-wide association studies using predicted gene functions. | Pers TH et al. | β | 2015 | β |
| Characterization of TCF21 Downstream Target Regions Identifies a Transcriptional Network Linking Multiple Independent Coronary Artery Disease Loci. | Sazonova O et al. | β | 2015 | β |
| Commentary: Consistency and collapsibility: are they crucial for instrumental variable analysis with a survival outcome in mendelian randomization? | Burgess S | β | 2015 | β |
| Commentary: Please sir, I want some more (and something else). | Garza C | β | 2015 | β |
| Common genetic variants influence human subcortical brain structures. | Hibar DP et al. | β | 2015 | β |
| Common VDR polymorphisms and idiopathic short stature in children from northern Greece. | Emmanouilidou E et al. | β | 2015 | β |
| Comparison of Twin and Extended Pedigree Designs for Obtaining Heritability Estimates. | Docherty AR et al. | β | 2015 | β |
| Composite Selection Signals for Complex Traits Exemplified Through Bovine Stature Using Multibreed Cohorts of European and African Bos taurus. | Randhawa IA et al. | β | 2015 | β |
| Contrasting genetic architectures in different mouse reference populations used for studying complex traits. | Buchner DA et al. | β | 2015 | β |
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| Covariation between human pelvis shape, stature, and head size alleviates the obstetric dilemma. | Fischer B et al. | β | 2015 | β |
| Detection of convergent genome-wide signals of adaptation to tropical forests in humans. | Amorim CE et al. | β | 2015 | β |
| Directional dominance on stature and cognition inΒ diverse human populations. | Joshi PK et al. | β | 2015 | β |
| DISSECT: A new tool for analyzing extremely large genomic datasets | Canela-Xandri O et al. | β | 2015 | β |
| DISTMIX: direct imputation of summary statistics for unmeasured SNPs from mixed ethnicity cohorts. | Lee D et al. | β | 2015 | β |
| Effectiveness of shrinkage and variable selection methods for the prediction of complex human traits using data from distantly related individuals. | Berger S et al. | β | 2015 | β |
| Epigenetic regulation of puberty via Zinc finger protein-mediated transcriptional repression. | Lomniczi A et al. | β | 2015 | β |
| eQTL mapping identifies insertion- and deletion-specific eQTLs in multiple tissues. | Huang J et al. | β | 2015 | β |
| Explicit Modeling of Ancestry Improves Polygenic Risk Scores and BLUP Prediction. | Chen CY et al. | β | 2015 | β |
| FGF signalling regulates bone growth through autophagy. | Cinque L et al. | β | 2015 | β |
| Forensic DNA Phenotyping: Predicting human appearance from crime scene material for investigative purposes. | Kayser M | β | 2015 | β |
| From caveman companion to medical innovator: genomic insights into the origin and evolution of domestic dogs. | Parker HG et al. | β | 2015 | β |
| Genetically determined height and coronary artery disease. | Nelson CP et al. | β | 2015 | β |
| Genetic analyses benefit from using less heterogeneous phenotypes: an illustration with the hospital anxiety and depression scale (HADS). | Laurin CA et al. | β | 2015 | β |
| Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53949). | Davies G et al. | β | 2015 | β |
| Genetic Determinants of Metabolism and Benign Prostate Enlargement: Associations with Prostate Volume. | Giri A et al. | β | 2015 | β |
| Genetic Regulation of Puberty Timing in Humans. | Day FR et al. | β | 2015 | β |
| Genetics of coronary artery disease: Short people at risk? | Trenkwalder T et al. | β | 2015 | β |
| Genetics of diabetic nephropathy: a long road of discovery. | McKnight AJ et al. | β | 2015 | β |
| Genetics of the dentofacial variation in human malocclusion. | Moreno Uribe LM et al. | β | 2015 | β |
| Genetic studies of body mass index yield new insights for obesity biology. | Locke AE et al. | β | 2015 | β |
| Genetic studies of schizophrenia: an update. | Chen J et al. | β | 2015 | β |
| Genome-wide Analysis of Body Proportion Classifies Height-Associated Variants by Mechanism of Action and Implicates Genes Important for Skeletal Development. | Chan Y et al. | β | 2015 | β |
| Genome-wide association analysis demonstrates the highly polygenic character of age-related hearing impairment. | Fransen E et al. | β | 2015 | β |
| Genome-Wide Association Analysis for Blood Lipid Traits Measured in Three Pig Populations Reveals a Substantial Level of Genetic Heterogeneity. | Yang H 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 |
| Genome-Wide Association and Trans-ethnic Meta-Analysis for Advanced Diabetic Kidney Disease: Family Investigation of Nephropathy and Diabetes (FIND). | Iyengar SK et al. | β | 2015 | β |
| Genome-Wide Association Studies and Liver Disease. | Speliotes EK | β | 2015 | β |
| Genome-wide association study dissects genetic architecture underlying longitudinal egg weights in chickens. | Yi G et al. | β | 2015 | β |
| Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: the CREAM consortium. | Li Q et al. | β | 2015 | β |
| Genome-wide association study of body weight in Australian Merino sheep reveals an orthologous region on OAR6 to human and bovine genomic regions affecting height and weight. | Al-Mamun HA et al. | β | 2015 | β |
| Genome-wide interaction analysis reveals replicated epistatic effects on brain structure. | Hibar DP et al. | β | 2015 | β |
| Genome-wide patterns of selection in 230 ancient Eurasians. | Mathieson I et al. | β | 2015 | β |
| Genome-Wide Scan for Adaptive Divergence and Association with Population-Specific Covariates. | Gautier M | β | 2015 | β |
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| Ghrelin. | MΓΌller TD et al. | β | 2015 | β |
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| Height and Breast Cancer Risk: Evidence From Prospective Studies and Mendelian Randomization. | Zhang B et al. | β | 2015 | β |
| Height-reducing variants and selection for short stature in Sardinia. | Zoledziewska M et al. | β | 2015 | β |
| Heterogeneity of genetic architecture of body size traits in a free-living population. | BΓ©rΓ©nos C et al. | β | 2015 | β |
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| How Genetic and Other Biological Factors Interact with Smoking Decisions. | Bierut L et al. | β | 2015 | β |
| Identification and validation of N-acetyltransferase 2 as an insulin sensitivity gene. | Knowles JW et al. | β | 2015 | β |
| Impact of HSD11B1 polymorphisms on BMI and components of the metabolic syndrome in patients receiving psychotropic treatments. | Quteineh L et al. | β | 2015 | β |
| Improving accuracy of rare variant imputation with a two-step imputation approach. | Kreiner-MΓΈller E et al. | β | 2015 | β |
| Increased Bone Turnover and Possible Accelerated Fracture Healing in a Murine Model With an Increased Circulating C-Type Natriuretic Peptide. | Kondo E et al. | β | 2015 | β |
| Independent evidence for an association between general cognitive ability and a genetic locus for educational attainment. | Trampush JW et al. | β | 2015 | β |
| Inferring positive selection in humans from genomic data. | Wollstein A et al. | β | 2015 | β |
| Inferring the economic standard of living and health from cohort height: Evidence from modern populations in developing countries. | Akachi Y et al. | β | 2015 | β |
| Influence of MCHR2 and MCHR2-AS1 Genetic Polymorphisms on Body Mass Index in Psychiatric Patients and In Population-Based Subjects with Present or Past Atypical Depression. | DelacrΓ©taz A et al. | β | 2015 | β |
| Insight in genome-wide association of metabolite quantitative traits by exome sequence analyses. | Demirkan A et al. | β | 2015 | β |
| Integrating basic research with prevention/intervention to reduce risky substance use among college students. | Dick DM et al. | β | 2015 | β |
| Integrating Diverse Types of Genomic Data to Identify Genes that Underlie Adverse Pregnancy Phenotypes. | Hirbo J et al. | β | 2015 | β |
| Intelligence: shared genetic basis between Mendelian disorders and a polygenic trait. | FraniΔ S et al. | β | 2015 | β |
| Intergenerational influences on the growth of Maya children: The effect of living conditions experienced by mothers and maternal grandmothers during their childhood. | Azcorra H et al. | β | 2015 | β |
| IRF4, MC1R and TYR genes are risk factors for actinic keratosis independent of skin color. | Jacobs LC et al. | β | 2015 | β |
| JAG: A Computational Tool to Evaluate the Role of Gene-Sets in Complex Traits. | Lips ES et al. | β | 2015 | β |
| LD Score regression distinguishes confounding from polygenicity in genome-wide association studies. | Bulik-Sullivan BK et al. | β | 2015 | β |
| Leveraging Multi-ethnic Evidence for Mapping Complex Traits in Minority Populations: An Empirical Bayes Approach. | Coram MA et al. | β | 2015 | β |
| MAGMA: generalized gene-set analysis of GWAS data. | de Leeuw CA et al. | β | 2015 | β |
| MAP4-dependent regulation of microtubule formation affects centrosome, cilia, and Golgi architecture as a central mechanism in growth regulation. | Zahnleiter D et al. | β | 2015 | β |
| Mapping of Craniofacial Traits in Outbred Mice Identifies Major Developmental Genes Involved in Shape Determination. | Pallares LF et al. | β | 2015 | β |
| Mendelian Randomization: New Applications in the Coming Age of Hypothesis-Free Causality. | Evans DM et al. | β | 2015 | β |
| Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. | Bowden J et al. | β | 2015 | β |
| Meta-analysis of correlated traits via summary statistics from GWASs with an application in hypertension. | Zhu X et al. | β | 2015 | β |
| Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci. | He M et al. | β | 2015 | β |
| Methodological Considerations in Estimation of Phenotype Heritability Using Genome-Wide SNP Data, Illustrated by an Analysis of the Heritability of Height in a Large Sample of African Ancestry Adults. | Chen F et al. | β | 2015 | β |
| MicroRNAs enrichment in GWAS of complex human phenotypes. | Goulart LF et al. | β | 2015 | β |
| "Missing" G x E Variation Controls Flowering Time in Arabidopsis thaliana. | Sasaki E et al. | β | 2015 | β |
| Modeling Linkage Disequilibrium Increases Accuracy of Polygenic Risk Scores. | VilhjΓ‘lmsson BJ et al. | β | 2015 | β |
| New genetic loci link adipose and insulin biology to body fat distribution. | Shungin D et al. | β | 2015 | β |
| NF-ΞΊB increased expression of 17Ξ²-hydroxysteroid dehydrogenase 4 promotes HepG2 proliferation via inactivating estradiol. | Lu X et al. | β | 2015 | β |
| Non-synonymous FGD3 Variant as Positional Candidate for Disproportional Tall Stature Accounting for a Carcass Weight QTL (CW-3) and Skeletal Dysplasia in Japanese Black Cattle. | Takasuga A et al. | β | 2015 | β |
| Novel insights into the genetics of smoking behaviour, lung function, and chronic obstructive pulmonary disease (UK BiLEVE): a genetic association study in UK Biobank. | Wain LV et al. | β | 2015 | β |
| Older individuals heterozygous for a growth hormone-releasing hormone receptor gene mutation are shorter than normal subjects. | Aguiar-Oliveira MH et al. | β | 2015 | β |
| Partitioning heritability by functional annotation using genome-wide association summary statistics. | Finucane HK et al. | β | 2015 | β |
| Partitioning of genomic variance reveals biological pathways associated with udder health and milk production traits in dairy cattle. | Edwards SM et al. | β | 2015 | β |
| Perspectives on Human Variation through the Lens of Diversity and Race. | Chakravarti A | β | 2015 | β |
| Pervasive pleiotropy between psychiatric disorders and immune disorders revealed by integrative analysis of multiple GWAS. | Wang Q et al. | β | 2015 | β |
| Population genetic differentiation of height and body mass index across Europe. | Robinson MR et al. | β | 2015 | β |
| Population Variation Reveals Independent Selection toward Small Body Size in Chinese Debao Pony. | Kader A et al. | β | 2015 | β |
| Recent developments in genome and exome-wide analyses of plasma lipids. | Lange LA et al. | β | 2015 | β |
| Regulation of body growth. | Lui JC et al. | β | 2015 | β |
| Selecting causal genes from genome-wide association studies via functionally coherent subnetworks. | TaΕan M et al. | β | 2015 | β |
| Serum lipid levels, body mass index, and their role in coronary artery calcification: a polygenic analysis. | van Setten J et al. | β | 2015 | β |
| Short and tall stature: a new paradigm emerges. | Baron J et al. | β | 2015 | β |
| Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation. | Soler Artigas M et al. | β | 2015 | β |
| SNPsnap: a Web-based tool for identification and annotation of matched SNPs. | Pers TH et al. | β | 2015 | β |
| Spag17 deficiency results in skeletal malformations and bone abnormalities. | Teves ME et al. | β | 2015 | β |
| Stanniocalcin-2 inhibits mammalian growth by proteolytic inhibition of the insulin-like growth factor axis. | Jepsen MR et al. | β | 2015 | β |
| Takayasu arteritis and ulcerative colitis: high rate of co-occurrence and genetic overlap. | Terao C et al. | β | 2015 | β |
| Temperature- and sex-related effects of serine protease alleles on larval development in the Glanville fritillary butterfly. | Ahola V et al. | β | 2015 | β |
| The CODATwins Project: The Cohort Description of Collaborative Project of Development of Anthropometrical Measures in Twins to Study Macro-Environmental Variation in Genetic and Environmental Effects on Anthropometric Traits. | Silventoinen K et al. | β | 2015 | β |
| The effects of height and BMI on prostate cancer incidence and mortality: a Mendelian randomization study in 20,848 cases and 20,214 controls from the PRACTICAL consortium. | Davies NM et al. | β | 2015 | β |
| The FlyCatwalk: a high-throughput feature-based sorting system for artificial selection in Drosophila. | Medici V et al. | β | 2015 | β |
| The Fourth Law of Behavior Genetics. | Chabris CF et al. | β | 2015 | β |
| The Genome-Wide Influence on Human BMI Depends on Physical Activity, Life Course, and Historical Period. | Guo G et al. | β | 2015 | β |
| The IGF1 P2 promoter is an epigenetic QTL for circulating IGF1 and human growth. | Ouni M et al. | β | 2015 | β |
| The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study. | Winkler TW et al. | β | 2015 | β |
| The many weak instruments problem and Mendelian randomization. | Davies NM et al. | β | 2015 | β |
| The Nature of Genetic Variation for Complex Traits Revealed by GWAS and Regional Heritability Mapping Analyses. | Caballero A et al. | β | 2015 | β |
| The Power of Theory, Research Design, and Transdisciplinary Integration in Moving Psychopathology Forward. | Vaidyanathan U et al. | β | 2015 | β |
| The Psychiatric Genomics Consortium Posttraumatic Stress Disorder Workgroup: Posttraumatic Stress Disorder Enters the Age of Large-Scale Genomic Collaboration. | Logue MW et al. | β | 2015 | β |
| Transcriptome Analysis in Domesticated Species: Challenges and Strategies. | Hekman JP et al. | β | 2015 | β |
| Two further patients with the 1q24 deletion syndrome expand the phenotype: A possible role for the miR199-214 cluster in the skeletal features of the condition. | Ashraf T et al. | β | 2015 | β |
| A Bayesian method to incorporate hundreds of functional characteristics with association evidence to improve variant prioritization. | Gagliano SA et al. | β | 2014 | β |
| A ChIP-seq-defined genome-wide map of MEF2C binding reveals inflammatory pathways associated with its role in bone density determination. | Johnson ME et al. | β | 2014 | β |
| Adaptations to local environments in modern human populations. | Jeong C et al. | β | 2014 | β |
| Adaptive, convergent origins of the pygmy phenotype in African rainforest hunter-gatherers. | Perry GH et al. | β | 2014 | β |
| Admixture in Latin America: geographic structure, phenotypic diversity and self-perception of ancestry based on 7,342 individuals. | Ruiz-Linares A et al. | β | 2014 | β |
| A draft de novo genome assembly for the northern bobwhite (Colinus virginianus) reveals evidence for a rapid decline in effective population size beginning in the Late Pleistocene. | Halley YA et al. | β | 2014 | β |
| Advantages and pitfalls in the application of mixed-model association methods. | Yang J et al. | β | 2014 | β |
| A genetic approach of wine yeast fermentation capacity in nitrogen-starvation reveals the key role of nitrogen signaling. | Brice C et al. | β | 2014 | β |
| A genome-wide association meta-analysis of preschool internalizing problems. | Benke KS et al. | β | 2014 | β |
| A genome-wide association study identifies a functional ERAP2 haplotype associated with birdshot chorioretinopathy. | Kuiper JJ et al. | β | 2014 | β |
| A genome-wide association study of limb bone length using a Large WhiteβΓβMinzhu intercross population. | Zhang LC et al. | β | 2014 | β |
| Allele-specific network reveals combinatorial interaction that transcends small effects in psoriasis GWAS. | Climer S et al. | β | 2014 | β |
| All humans, great or small, short or tall. | Poot M | β | 2014 | β |
| A low-frequency variant in MAPK14 provides mechanistic evidence of a link with myeloperoxidase: a prognostic cardiovascular risk marker. | Waterworth DM et al. | β | 2014 | β |
| A meta-analysis of gene expression quantitative trait loci in brain. | Kim Y et al. | β | 2014 | β |
| Analysis of coding variants identified from exome sequencing resources for association with diabetic and non-diabetic nephropathy in African Americans. | Bailey JNC et al. | β | 2014 | β |
| An evaluation of high-throughput approaches to QTL mapping in Saccharomyces cerevisiae. | Wilkening S et al. | β | 2014 | β |
| An evolving perspective about the origins of childhood undernutrition and nutritional interventions that includes the gut microbiome. | Ahmed T et al. | β | 2014 | β |
| Angiotensin-converting enzyme genetic polymorphism: its impact on cardiac remodeling. | Albuquerque FN et al. | β | 2014 | β |
| A polygenic risk score associated with measures of depressive symptoms among older adults. | Levine ME et al. | β | 2014 | β |
| A population genetic signal of polygenic adaptation. | Berg JJ et al. | β | 2014 | β |
| Applications of population genetics to animal breeding, from wright, fisher and lush to genomic prediction. | Hill WG | β | 2014 | β |
| Applying compressed sensing to genome-wide association studies. | Vattikuti S et al. | β | 2014 | β |
| A prospective study of height and body mass index in childhood, birth weight, and risk of adult glioma over 40 years of follow-up. | Kitahara CM et al. | β | 2014 | β |
| A simulation study of gene-by-environment interactions in GWAS implies ample hidden effects. | Marigorta UM et al. | β | 2014 | β |
| Assessing the utility of intermediate phenotypes for genetic mapping of psychiatric disease. | Flint J et al. | β | 2014 | β |
| Association of height and violent criminality: results from a Swedish total population study. | Beckley AL et al. | β | 2014 | β |
| Asthma genetics 2014: reaching for high-hanging fruit. | Koppelman GH et al. | β | 2014 | β |
| Biological insights from 108 schizophrenia-associated genetic loci. | Schizophrenia Working Group of the Psychiatric Genomics Consortium | β | 2014 | β |
| Cell type-specific expression analysis to identify putative cellular mechanisms for neurogenetic disorders. | Xu X et al. | β | 2014 | β |
| Challenges and prospects in genome-wide quantitative trait loci mapping of standing genetic variation in natural populations. | Schielzeth H et al. | β | 2014 | β |
| Clinical features of a new acid-labile subunit (IGFALS) heterozygous mutation: anthropometric and biochemical characterization and response to growth hormone administration. | Grandone A et al. | β | 2014 | β |
| Common DNA variants predict tall stature in Europeans. | Liu F et al. | β | 2014 | β |
| Common genetic variants associated with cognitive performance identified using the proxy-phenotype method. | Rietveld CA et al. | β | 2014 | β |
| Comparative epigenomics: defining and utilizing epigenomic variations across species, time-course, and individuals. | Xiao S et al. | β | 2014 | β |
| Compression and fast retrieval of SNP data. | Sambo F et al. | β | 2014 | β |
| Cooperation between phenotypic plasticity and genetic mutations can account for the cumulative selection in evolution. | Nishikawa K et al. | β | 2014 | β |
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