Novel common copy number variation for early onset extreme obesity on chromosome 11q11 identified by a genome-wide analysis.
- Authors
- Jarick, Ivonne; Vogel, Carla I G; Scherag, Susann; Schäfer, Helmut; Hebebrand, Johannes; Hinney, Anke; Scherag, André
- Year
- 2011
- Journal
- Human molecular genetics
- PMID
- 21131291
- DOI
- 10.1093/hmg/ddq518
- PMCID
- PMC3024044
Heritability of obesity is substantial and recent meta-analyses of genome-wide association studies (GWASs) have been successful in detecting several robustly associated genomic regions for obesity using single-nucleotide polymorphisms (SNPs). However, taken together, the SNPs explain only a small proportion of the overall heritability. Copy number variations (CNVs) might contribute to the 'missing heritability'. We searched genome-wide for association between common CNVs and early-onset extreme obesity. Four hundred and twenty-four case-parents obesity trios and an independent sample of 453 extremely obese children and adolescents and 435 normal-weight and lean adult controls were genotyped by the Affymetrix Genome-Wide Human SNP Array 6.0. We detected 20 common copy number variable regions (CNVRs) which were associated with obesity. The most promising CNVRs were followed-up in an independent sample of 365 obesity trios, confirming the association for two candidate CNVRs. We identified a common CNVR exclusively covering the three olfactory receptor genes OR4P4, OR4S2 and OR4C6 to be associated with obesity (combined P-value = 0.015 in a total of 789 families; odds ratio for the obesity effect allele = 1.19; 95% confidence interval = 1.016-1.394). We also replicated two common deletions (near NEGR1 and at chromosome 10q11.22) that have previously been reported to be associated with body weight. Additionally, we support a rare CNV on chromosome 16 that has recently been reported by two independent groups. However, rare CNVs had not been the focus of our study. We conclude that common CNVs are unlikely to contribute substantially to the genetic basis of early-onset extreme obesity.
Study design to discover CNVRs associated with (early-onset extreme) obesity.
LLM interpretation
This figure is a flow diagram illustrating a two-stage study design (Discovery and Replication) to identify copy number variation regions (CNVRs) associated with early-onset extreme obesity. The discovery phase utilizes family-based and case-control GWAS samples to narrow 244 common autosomal CNVRs down to 20 directionally consistent candidates. The replication phase uses two independent family-based samples to confirm 2 CNVRs and provide suggestive support for 4 others, ultimately resulting in the re-confirmation of 2 previously known CNVRs and the identification of 1 new CNVR.
Genome-wide distribution of the 244 common CNVRs estimated in our discovery GWAS (family-based and case–control) samples. CNVRs are graphically represented by black bars according to their chromosomal position and size (genome build hg 18).
LLM interpretation
This figure is a genome-wide map showing the distribution of 244 common copy number variation regions (CNVRs) across human chromosomes 1 through 22. The chromosomes are represented as horizontal grey bars, with CNVRs indicated by black vertical bars positioned according to their chromosomal location and size. The y-axis is labeled "Chromosome," and the visualization illustrates the relative density and spread of these variations across the genome.
Results for CNVR 11q11 in the family-based (filled circles) and in the case–control (open circles) GWAS discovery sample. Additionally, multi-marker FBAT results are plotted as grey lines representing the P-values achieved in the test incorporating each CNV marker covered by the line.
LLM interpretation
This is a scatter plot showing $-\log_{10}$ (one-sided p-values) against the position on chromosome 11 in Mb for CNVR 11q11. The data includes family-based results (filled circles), case-control results (open circles), and multi-marker FBAT results (grey lines). Most data points and lines cluster between 0 and 2 on the y-axis, with a few case-control outliers reaching values between 3 and 5.
Results for CNVR 1p31.1 (20 kb upstream of NEGR1) in the family-based (filled circles) and in the case–control (open circles) GWAS discovery sample. Additionally, multi-marker FBAT results are plotted as grey lines representing the P-values achieved in the test incorporating each CNV marker covered by a line.
LLM interpretation
This is a scatter plot showing $-\log_{10}$ (one-sided p-values) against the position on chromosome 1 in Mb for CNVR 1p31.1. The data includes family-based results (filled circles), case-control results (open circles), and multi-marker FBAT results (grey lines). Most data points fall between 0 and 2 on the y-axis, with the highest p-value significance reaching just above 2.
Results for CNVR 10q11.22 (1) in the family-based (filled circles) and in the case–control (open circles) GWAS discovery sample. Additionally, multi-marker FBAT results are plotted as grey lines representing the P-values achieved in the test incorporating each CNV marker covered by a line.
LLM interpretation
This is a scatter plot showing $-\log_{10}$ (one-sided p-values) against the position on chromosome 10 in Mb for CNVR 10q11.22 (1). The data includes family-based results (filled circles) and case-control results (open circles), with the latter showing a prominent peak of higher significance around 46.45–46.5 Mb. Additionally, grey lines represent multi-marker FBAT results, indicating p-values for tests incorporating various CNV markers.
No entities extracted from this document yet.
No uploaded files.
In this knowledge base
| Title | Year | PMID |
|---|---|---|
| On the association of common and rare genetic variation influencing body mass index: a combined SNP and CNV analysis. | 2014 | 24884913 |
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| The Emerging Role of Olfactory Receptors: From Genomics to Precision Medicine. | Dubey N et al. | — | 2026 | → |
| Common-variant and rare-variant genetic architecture of heart failure across the allele-frequency spectrum. | Lee DSM et al. | — | 2025 | → |
| Obesity genetic association prospective cohort utilizing single center real-world evidence data. | Bağci Ö et al. | — | 2025 | → |
| Olfactory Receptor Gene Deletions: A Novel Genetic Findings in Idiopathic Prepubertal Gynecomastia and Juvenile Macromastia. | Bas F et al. | — | 2025 | → |
| The Interplay of UCP3 and PCSK1 Variants in Severe Obesity. | Verde L et al. | — | 2025 | → |
| Towards Precision Medicine in Obesity: Genetic Copy Number Variations Profiling Linked to Specific Metabolic Dysregulation Patterns. | Mitu I et al. | — | 2025 | → |
| Illuminating the neuropeptide Y<sub>4</sub> receptor and its ligand pancreatic polypeptide from a structural, functional, and therapeutic perspective. | Schüß C et al. | — | 2024 | → |
| <i>AGAP</i> duplicons associate with structural diversity at Chromosome 10q11.22. | Fornezza S et al. | — | 2024 | → |
| The complex web of obesity: from genetics to precision medicine. | M JN et al. | — | 2024 | → |
| The olfactory bulb: A neuroendocrine spotlight on feeding and metabolism. | Stark R | — | 2024 | → |
| Exploring quantitative traits-associated copy number deletions through reanalysis of UK10K consortium whole genome sequencing cohorts. | Lee S et al. | — | 2023 | → |
| [From genotype to phenotype: amylase gene in childhood obesity]. | Vázquez-Moreno MA et al. | — | 2023 | → |
| GeneToCN: an alignment-free method for gene copy number estimation directly from next-generation sequencing reads | Pajuste F et al. | — | 2023 | — |
| GeneToCN: an alignment-free method for gene copy number estimation directly from next-generation sequencing reads. | Pajuste FD et al. | — | 2023 | → |
| The Role of the Olfactory System in Obesity and Metabolism in Humans: A Systematic Review and Meta-Analysis. | Matiashova L et al. | — | 2023 | → |
| Uncovering structural variants associated with body weight and obesity risk in labrador retrievers: a genome-wide study. | Antkowiak M et al. | — | 2023 | → |
| The genetics of obesity: from discovery to biology. | Loos RJF et al. | — | 2022 | → |
| A Genome-Wide Association Study of Childhood Body Fatness. | Warner ET et al. | — | 2021 | → |
| Effect of interaction between obesity-promoting genetic variants and behavioral factors on the risk of obese phenotypes. | Rana S et al. | — | 2021 | → |
| [Genetic Analyses of Complex Phenotypes Through the Example of Anorexia Nervosa and Bodyweight Regulation]. | Hirtz R et al. | — | 2021 | → |
| High Olfactory Receptor-Rich 11q11 Copy Number in Girls and African American Children. | Phillips M et al. | — | 2021 | → |
| Predicting anthropometric and metabolic traits with a genetic risk score for obesity in a sample of Pakistanis. | Rana S et al. | — | 2021 | → |
| Copy number variant analysis and expression profiling of the olfactory receptor-rich 11q11 region in obesity predisposition. | Diels S et al. | — | 2020 | → |
| Copy number variants in lipid metabolism genes are associated with gallstones disease in men. | Pérez-Palma E et al. | — | 2020 | → |
| Depression-Associated Gene <i>Negr1-Fgfr2</i> Pathway Is Altered by Antidepressant Treatment. | Carboni L et al. | — | 2020 | → |
| From Bound Cells Comes a Sound Mind: The Role of Neuronal Growth Regulator 1 in Psychiatric Disorders. | Noh K et al. | — | 2020 | → |
| Heterozygous rare genetic variants in non-syndromic early-onset obesity. | Serra-Juhé C et al. | — | 2020 | → |
| Highly Conserved Molecular Features in IgLONs Contrast Their Distinct Structural and Biological Outcomes. | Venkannagari H et al. | — | 2020 | → |
| Obesity and COVID-19: Oro-Naso-Sensory Perception. | Khan AS et al. | — | 2020 | → |
| Association of Salivary Amylase (<i>AMY1</i>) Gene Copy Number with Obesity in Alabama Elementary School Children. | Venkatapoorna CMK et al. | — | 2019 | → |
| Associations between olfactory pathway gene methylation marks, obesity features and dietary intakes. | Ramos-Lopez O et al. | — | 2019 | → |
| Copy number determination of the gene for the human pancreatic polypeptide receptor NPY4R using read depth analysis and droplet digital PCR. | Shebanits K et al. | — | 2019 | → |
| Established and emerging strategies to crack the genetic code of obesity. | Tam V et al. | — | 2019 | → |
| Genetic variation of FTO: rs1421085 T>C, rs8057044 G>A, rs9939609 T>A, and copy number (CNV) in Mexican Mayan school-aged children with obesity/overweight and with normal weight. | González-Herrera L et al. | — | 2019 | → |
| Therapeutic potential of ectopic olfactory and taste receptors. | Lee SJ et al. | — | 2019 | → |
| Clinical significance of germline copy number variation in susceptibility of human diseases. | Hu L et al. | — | 2018 | → |
| Copy number of pancreatic polypeptide receptor gene NPY4R correlates with body mass index and waist circumference. | Shebanits K et al. | — | 2018 | → |
| Ethnic and population differences in the genetic predisposition to human obesity. | Stryjecki C et al. | — | 2018 | → |
| Genome organization: connecting the developmental origins of disease and genetic variation. | Jacobson E et al. | — | 2018 | → |
| Low Salivary Amylase Gene (<i>AMY1</i>) Copy Number Is Associated with Obesity and Gut <i>Prevotella</i> Abundance in Mexican Children and Adults. | León-Mimila P et al. | — | 2018 | → |
| Spatial maps of prostate cancer transcriptomes reveal an unexplored landscape of heterogeneity. | Berglund E et al. | — | 2018 | → |
| The Effect of SH2B1 Variants on Expression of Leptin- and Insulin-Induced Pathways in Murine Hypothalamus. | Giuranna J et al. | — | 2018 | → |
| Copy Number Variations in Candidate Genes and Intergenic Regions Affect Body Mass Index and Abdominal Obesity in Mexican Children. | Antúnez-Ortiz DL et al. | — | 2017 | → |
| Novel genes involved in severe early-onset obesity revealed by rare copy number and sequence variants. | Serra-Juhé C et al. | — | 2017 | → |
| Analysis of Genes Involved in Body Weight Regulation by Targeted Re-Sequencing. | Volckmar AL et al. | — | 2016 | → |
| CNV analysis and mutation screening indicate an important role for the NPY4R gene in human obesity. | Aerts E et al. | — | 2016 | → |
| Recent progress in genetics, epigenetics and metagenomics unveils the pathophysiology of human obesity. | Pigeyre M et al. | — | 2016 | → |
| The cilium: a cellular antenna with an influence on obesity risk. | Mariman EC et al. | — | 2016 | → |
| A Copy Number Variant on Chromosome 20q13.3 Implicated in Thinness and Severe Obesity. | Hasstedt SJ et al. | — | 2015 | → |
| CPAS: a trans-omics pathway analysis tool for jointly analyzing DNA copy number variations and mRNA expression profiles data. | Zhang F et al. | — | 2015 | → |
| Fine Mapping of a GWAS-Derived Obesity Candidate Region on Chromosome 16p11.2. | Volckmar AL et al. | — | 2015 | → |
| [Genetic and epigenetic mechanisms in obesity]. | Hinney A et al. | — | 2015 | → |
| Genome Wide Distributions and Functional Characterization of Copy Number Variations between Chinese and Western Pigs. | Wang H et al. | — | 2015 | → |
| Interaction association analysis of imputed SNPs in case-control and follow-up studies. | Subirana I et al. | — | 2015 | → |
| Interactions between obesity-related copy number variants and dietary behaviors in childhood obesity. | Zhang D et al. | — | 2015 | → |
| Obesity and genomics: role of technology in unraveling the complex genetic architecture of obesity. | Apalasamy YD et al. | — | 2015 | → |
| Olfactory receptor genes cooperate with protocadherin genes in human extreme obesity. | Mariman EC et al. | — | 2015 | → |
| The ethnoepidemiology of obesity. | Valera B et al. | — | 2015 | → |
| The Genetics of Pediatric Obesity. | Chesi A et al. | — | 2015 | → |
| A genome-wide association study on copy-number variation identifies a 11q11 loss as a candidate susceptibility variant for colorectal cancer. | Fernandez-Rozadilla C et al. | — | 2014 | → |
| Analysis of genome-wide copy number variations in Chinese indigenous and western pig breeds by 60 K SNP genotyping arrays. | Wang Y et al. | — | 2014 | → |
| Etiology of Obesity Over the Life Span: Ecological and Genetic Highlights from Asian Countries. | Chong PN et al. | — | 2014 | → |
| Genome-wide copy number variation study and gene expression analysis identify ABI3BP as a susceptibility gene for Kashin-Beck disease. | Zhang F et al. | — | 2014 | → |
| Identification of structural variation in mouse genomes. | Keane TM et al. | — | 2014 | → |
| Low copy number of the salivary amylase gene predisposes to obesity. | Falchi M et al. | — | 2014 | → |
| Novel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index. | Hoggart CJ et al. | — | 2014 | → |
| Obesity gene NEGR1 associated with white matter integrity in healthy young adults. | Dennis EL et al. | — | 2014 | → |
| On the association of common and rare genetic variation influencing body mass index: a combined SNP and CNV analysis. | Peterson RE et al. | — | 2014 | → |
| The genetics of human obesity. | Waalen J | — | 2014 | → |
| A 680 kb duplication at the FTO locus in a kindred with obesity and a distinct body fat distribution. | Davies RW et al. | — | 2013 | → |
| Combined linkage and association analyses identify a novel locus for obesity near PROX1 in Asians. | Kim HJ et al. | — | 2013 | → |
| Copy number variation on chromosome 10q26.3 for obesity identified by a genome-wide study. | Yang TL et al. | — | 2013 | → |
| Copy number variations of obesity relevant loci associated with body mass index in young Chinese. | Sun C et al. | — | 2013 | → |
| Ethnic differentiation of copy number variation on chromosome 16p12.3 for association with obesity phenotypes in European and Chinese populations. | Yang TL et al. | — | 2013 | → |
| From obesity genetics to the future of personalized obesity therapy. | El-Sayed Moustafa JS et al. | — | 2013 | → |
| Gene-based copy number variation study reveals a microdeletion at 12q24 that influences height in the Korean population. | Kim YK et al. | — | 2013 | → |
| KGVDB: a population-based genomic map of CNVs tagged by SNPs in Koreans. | Moon S et al. | — | 2013 | → |
| Molecular genetic aspects of weight regulation. | Hebebrand J et al. | — | 2013 | → |
| Rare genomic structural variants in complex disease: lessons from the replication of associations with obesity. | Walters RG et al. | — | 2013 | → |
| Sex bias in copy number variation of olfactory receptor gene family depends on ethnicity. | Shadravan F | — | 2013 | → |
| Utilizing extended pedigree information for discovery and confirmation of copy number variable regions among Mexican Americans. | Blackburn A et al. | — | 2013 | → |
| Beyond the fourth wave of genome-wide obesity association studies. | Sandholt CH et al. | — | 2012 | → |
| Copy number variants in obesity-related syndromes: review and perspectives on novel molecular approaches. | D'Angelo CS et al. | — | 2012 | → |
| Copy number variations associated with obesity-related traits in African Americans: a joint analysis between GENOA and HyperGEN. | Zhao W et al. | — | 2012 | → |
| Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human. | Ichimura A et al. | — | 2012 | → |
| Genome-wide association study identifies a maternal copy-number deletion in PSG11 enriched among preeclampsia patients. | Zhao L et al. | — | 2012 | → |
| Integrating genomic and epigenomic information: a promising strategy for identifying functional DNA variants of human disease. | Zaina S et al. | — | 2012 | → |
| Mutation screen in the GWAS derived obesity gene SH2B1 including functional analyses of detected variants. | Volckmar AL et al. | — | 2012 | → |
| Olfaction under metabolic influences. | Palouzier-Paulignan B et al. | — | 2012 | → |
| The fine-scale architecture of structural variants in 17 mouse genomes. | Yalcin B et al. | — | 2012 | → |
| Aberrations of NEGR1 on 1p31 and MYEOV on 11q13 in neuroblastoma. | Takita J et al. | — | 2011 | → |
| Genetics of childhood obesity. | Zhao J et al. | — | 2011 | → |
| Genome-wide association of copy-number variation reveals an association between short stature and the presence of low-frequency genomic deletions. | Dauber A et al. | — | 2011 | → |
| Genome-wide mapping of copy number variation in humans: comparative analysis of high resolution array platforms. | Haraksingh RR et al. | — | 2011 | → |
| Molecular basis of obesity: current status and future prospects. | Choquet H et al. | — | 2011 | → |
| Programming towards childhood obesity. | Tounian P | — | 2011 | → |