Implication of European-derived adiposity loci in African Americans.
- Authors
- Hester, J M; Wing, M R; Li, J; Palmer, N D; Xu, J; Hicks, P J; Roh, B H; Norris, J M; Wagenknecht, L E; Langefeld, C D; Freedman, B I; Bowden, D W; Ng, M C Y
- Year
- 2012
- Journal
- International journal of obesity (2005)
- PMID
- 21750520
- DOI
- 10.1038/ijo.2011.131
- PMCID
- PMC3306054
OBJECTIVE: Recent genome-wide association studies (GWAS) have identified multiple novel loci associated with adiposity in European-derived study populations. Limited study of these loci has been reported in African Americans. Here we examined the effects of these previously identified adiposity loci in African Americans. METHODS: A total of 46 representative single-nucleotide polymorphisms (SNPs) in 19 loci that were previously reported in GWAS in Europeans (including FTO and MC4R) were genotyped in 4992 subjects from six African-American cohorts. These SNPs were tested for association with body mass index (BMI) after adjustment for age, gender, disease status and population structure in each cohort. Meta-analysis was conducted to combine the results. RESULTS: Meta-analysis of 4992 subjects revealed seven SNPs near four loci, including NEGR1, TMEM18, SH2B1 /ATP2A1 and MC4R, showing significant association at 0.005<P<0.05, and had effect sizes between 0.04 and 0.06 s.d. units (or 0.30 to 0.44β g m(-2)) of BMI for each copy of the BMI-increasing allele. The most significantly associated SNPs (rs9424977, rs3101336 and rs2568958) are located in the NEGR1 gene (P=0.005, 0.020 and 0.019, respectively). CONCLUSION: We replicated the association of variants at four loci in six African-American cohorts that demonstrated a consistent direction of association with previous studies of adiposity in Europeans. These loci are all highly expressed in the brain, consistent with an important role for central nervous system processes in weight regulation. However, further comprehensive examination of these regions may be necessary to fine map and elucidate for possible genetic differences between these two populations.
No figures extracted from this document.
| Name | Type |
|---|---|
| adiposity | phenotype |
| adiposity measures | phenotype |
| Affymetrix Genome-wide Human SNP array 6.0 | drug |
| African American | cohort |
| African-American cohorts local | cohort |
| African American Diabetes Heart Study local | cohort |
| African-Americans | cohort |
| African-derived populations local | cohort |
| age | phenotype |
| Ancestry informative markers local | phenotype |
| Asian | cohort |
| ATP2A1 | gene |
| BCDIN3D local | gene |
| Bdnf | gene |
| black men | cohort |
| black women | cohort |
| BMI | phenotype |
| BMI z-score | phenotype |
| body weight | phenotype |
| brain | anatomy |
| brain development | phenotype |
| C-allele local | variant |
| cancer | phenotype |
| CDH12 | gene |
| cell movement local | phenotype |
| CEU | cohort |
| childhood obesity | phenotype |
| CHST8 | gene |
| Cohort 3-6 local | cohort |
| community-based local | phenotype |
| coronary artery disease | phenotype |
| coronary heart disease | phenotype |
| CTNNBL1 | gene |
| Dgkg | anatomy |
| diabetes | phenotype |
| Diabetes Heart Studies cohort local | cohort |
| Diabetes Heart Study local | cohort |
| diabetic nephropathy local | phenotype |
| end-stage renal disease local | phenotype |
| ESRD local | phenotype |
| ETV5 | gene |
| European American children local | cohort |
| European ancestry | cohort |
| European-derived local | cohort |
| European-derived cohorts local | cohort |
| European-derived populations local | cohort |
| European population | cohort |
| Europeans | cohort |
| European studies | cohort |
| extreme obesity | phenotype |
| FAIM2 | gene |
| FTO | gene |
| Gallbladder Disease local | phenotype |
| genomic DNA | drug |
| glioma-directed stem cell migration local | phenotype |
| glucose homeostasis traits local | phenotype |
| GNPDA2 | gene |
| healthy controls | cohort |
| hyperinsulinemia | phenotype |
| hyperphagia | phenotype |
| hypertension | phenotype |
| hypothalamus | anatomy |
| Insulin Resistance Atherosclerosis (IRAS) Studies cohort local | cohort |
| iPLEX Sequenom MassARRAY local | drug |
| iPLEX Sequenom MassARRAY platform local | drug |
| IRAS Family Study local | cohort |
| IRAS Study local | cohort |
| KCTD15 | gene |
| leptin | drug |
| LGR4 local | gene |
| LIN7C | gene |
| liver disease | phenotype |
| LYPlAL1 | gene |
| MAF | gene |
| MC4R | gene |
| metabolic syndrome | phenotype |
| MSRA | gene |
| MTCH2 | gene |
| multiple African-American populations local | cohort |
| National Health and Nutrition Examination Survey 2003-2004 local | cohort |
| NEGR1 | gene |
| non-diabetic local | phenotype |
| Non-diabetic subjects local | phenotype |
| non-Hispanic whites | cohort |
| NPC1 | gene |
| NRXN3 | gene |
| obesity | phenotype |
| osteoarthritis | phenotype |
| PARD3B local | gene |
| PC1 | phenotype |
| Pcsk1 | gene |
| Pedcheck | drug |
| PRL local | gene |
| PTER | gene |
| RASAL2 local | gene |
| risk factor | phenotype |
| rs10508503 | variant |
| rs10871777 local | variant |
| rs12457166 local | variant |
| rs17782313 | variant |
| rs1942880 local | variant |
| rs2568958 local | variant |
| rs2867125 local | variant |
| rs3101336 local | variant |
| rs3751812 local | variant |
| rs4450508 local | variant |
| rs4712652 local | variant |
| rs476828 local | variant |
| rs477181 local | variant |
| rs571312 | variant |
| rs633265 local | variant |
| rs6567160 local | variant |
| rs7498665 | variant |
| rs8050136 | variant |
| rs94224977 local | variant |
| rs9424977 local | variant |
| rs9939609 | variant |
| SEC16B | gene |
| sex | phenotype |
| SFRS10 | gene |
| SH2B1 | gene |
| six African-American cohorts local | cohort |
| six cohorts local | cohort |
| Six Cohorts local | cohort |
| Sleep Disorders local | phenotype |
| SNP | cohort |
| SNPs_at_novel_adiposity_loci local | variant |
| stroke | phenotype |
| study cohort | cohort |
| sub-clinical cardiovascular risk local | phenotype |
| subjects with T2DM local | cohort |
| subjects with T2DM-ESRD local | cohort |
| T2DM | phenotype |
| T2DM-ESRD local | phenotype |
| T2DMβESRD local | phenotype |
| T-allele local | variant |
| TCF7L2 | gene |
| TFAP2B | gene |
| TMEM18 | gene |
| total fat | phenotype |
| type 2 diabetes | phenotype |
| visceral adipose tissue | phenotype |
| waist circumference | phenotype |
| waist-to-hip ratio | phenotype |
| weight regulation | phenotype |
| YRI | cohort |
No uploaded files.
In this knowledge base
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| The Association between Obesity Susceptibility and Polymorphisms of MC4R, SH2B1, and NEGR1 in Tibetans. | Huang T et al. | β | 2024 | β |
| "GENYAL" Study to Childhood Obesity Prevention: Methodology and Preliminary Results. | Marcos-Pasero H et al. | β | 2022 | β |
| <i>FTO</i> Common Obesity SNPs Interact with Actionable Environmental Factors: Physical Activity, Sugar-Sweetened Beverages and Wine Consumption. | Chermon D et al. | β | 2022 | β |
| Common genetic variants associated with obesity in an African-American and Hispanic/Latino population. | Chalazan B et al. | β | 2021 | β |
| Local ancestry prediction with <i>PyLAE</i>. | Moshkov N et al. | β | 2021 | β |
| From Bound Cells Comes a Sound Mind: The Role of Neuronal Growth Regulator 1 in Psychiatric Disorders. | Noh K et al. | β | 2020 | β |
| Genetics of Obesity in East Asians. | Sun C et al. | β | 2020 | β |
| Interaction between Metabolic Genetic Risk Score and Dietary Fatty Acid Intake on Central Obesity in a Ghanaian Population. | Alsulami S et al. | β | 2020 | β |
| Local Ancestry Prediction with<i>PyLAE</i> | Smetanin A et al. | β | 2020 | β |
| Genetic polymorphisms associated with type 2 diabetes in the Arab world: A systematic review and meta-analysis. | Abuhendi N et al. | β | 2019 | β |
| Genomics of Reproductive Traits and Cardiometabolic Disease Risk in African American Women. | Hardy TM et al. | β | 2019 | β |
| Maternal BMI-Increasing Genetic Risk Score and Fetal Weights among Diverse US Ethnic Groups. | Shrestha D et al. | β | 2019 | β |
| The association of the fat mass and obesity-associated gene (FTO) rs9939609 polymorphism and the severe obesity in a Brazilian population. | da Fonseca ACP et al. | β | 2019 | β |
| Genome-wide interaction with the insulin secretion locus MTNR1B reveals CMIP as a novel type 2 diabetes susceptibility gene in African Americans. | Keaton JM et al. | β | 2018 | β |
| The Effect of SH2B1 Variants on Expression of Leptin- and Insulin-Induced Pathways in Murine Hypothalamus. | Giuranna J et al. | β | 2018 | β |
| A global evolutionary and metabolic analysis of human obesity gene risk variants. | Castillo JJ et al. | β | 2017 | β |
| Association of gene coding variation and resting metabolic rate in a multi-ethnic sample of children and adults. | Hellwege JN et al. | β | 2017 | β |
| Gene-nutrient interactions and susceptibility to human obesity. | Castillo JJ et al. | β | 2017 | β |
| GENOME-WIDE INTERACTION WITH SELECTED TYPE 2 DIABETES LOCI REVEALS NOVEL LOCI FOR TYPE 2 DIABETES IN AFRICAN AMERICANS. | Keaton JM et al. | β | 2017 | β |
| Association of FTO rs9939609 SNP with Obesity and Obesity- Associated Phenotypes in a North Indian Population. | Prakash J et al. | β | 2016 | β |
| Genome-Wide Interaction with Insulin Secretion Loci Reveals Novel Loci for Type 2 Diabetes in African Americans. | Keaton JM et al. | β | 2016 | β |
| Fine Mapping of a GWAS-Derived Obesity Candidate Region on Chromosome 16p11.2. | Volckmar AL et al. | β | 2015 | β |
| Genetic association studies of obesity in Africa: a systematic review. | Yako YY et al. | β | 2015 | β |
| Insights into the Genetic Susceptibility to Type 2 Diabetes from Genome-Wide Association Studies of Obesity-Related Traits. | Karaderi T et al. | β | 2015 | β |
| Progressive influence of body mass index-associated genetic markers in rural Gambians. | Fulford AJ et al. | β | 2015 | β |
| Common variants in BDNF, FAIM2, FTO, MC4R, NEGR1, and SH2B1 show association with obesity-related variables in Spanish Roma population. | Poveda A et al. | β | 2014 | β |
| Genetic association study of adiposity and melanocortin-4 receptor (MC4R) common variants: replication and functional characterization of non-coding regions. | Evans DS et al. | β | 2014 | β |
| On the association of common and rare genetic variation influencing body mass index: a combined SNP and CNV analysis. | Peterson RE et al. | β | 2014 | β |
| Polygenic risk predicts obesity in both white and black young adults. | Domingue BW et al. | β | 2014 | β |
| SH2B1 in Ξ²-cells promotes insulin expression and glucose metabolism in mice. | Chen Z et al. | β | 2014 | β |
| SH2B1 in Ξ²-cells regulates glucose metabolism by promoting Ξ²-cell survival and islet expansion. | Chen Z et al. | β | 2014 | β |
| SH2B1 regulation of energy balance, body weight, and glucose metabolism. | Rui L | β | 2014 | β |
| The association of common variants in PCSK1 with obesity: a HuGE review and meta-analysis. | Stijnen P et al. | β | 2014 | β |
| The bigger picture of FTO: the first GWAS-identified obesity gene. | Loos RJ et al. | β | 2014 | β |
| A genome-wide search for type 2 diabetes susceptibility genes in an extended Arab family. | Al Safar HS et al. | β | 2013 | β |
| A systematic mapping approach of 16q12.2/FTO and BMI in more than 20,000 African Americans narrows in on the underlying functional variation: results from the Population Architecture using Genomics and Epidemiology (PAGE) study. | Peters U et al. | β | 2013 | β |
| Brain regulation of energy balance and body weight. | Rui L | β | 2013 | β |
| Genetics of obesity and type 2 diabetes in African Americans. | McCormack S et al. | β | 2013 | β |
| Leptin signaling and leptin resistance. | Zhou Y et al. | β | 2013 | β |
| Melanocortin-4 receptor in energy homeostasis and obesity pathogenesis. | Hinney A et al. | β | 2013 | β |
| Obesity genomics: assessing the transferability of susceptibility loci across diverse populations. | Lu Y et al. | β | 2013 | β |
| Obesity polymorphisms identified in genome-wide association studies interact with n-3 polyunsaturated fatty acid intake and modify the genetic association with adiposity phenotypes in Yup'ik people. | Lemas DJ et al. | β | 2013 | β |
| Transferability and fine mapping of type 2 diabetes loci in African Americans: the Candidate Gene Association Resource Plus Study. | Ng MC et al. | β | 2013 | β |
| Estimation of genetic effects on BMI during adolescence in an ethnically diverse cohort: The National Longitudinal Study of Adolescent Health. | Graff M et al. | β | 2012 | β |
| Functional inactivation of the genome-wide association study obesity gene neuronal growth regulator 1 in mice causes a body mass phenotype. | Lee AW et al. | β | 2012 | β |