'Racial' differences in genetic effects for complex diseases.
paper
Cited
Public
Unavailable
- Authors
- Ioannidis, John P A; Ntzani, Evangelia E; Trikalinos, Thomas A
- Year
- 2004
- Journal
- Nature genetics
- PMID
- 15543147
- DOI
- 10.1038/ng1474
'Racial' differences are frequently debated in clinical, epidemiological and molecular research and beyond. In particular, there is considerable controversy regarding the existence and importance of 'racial' differences in genetic effects for complex diseases influenced by a large number of genes. An important question is whether ancestry influences the impact of each gene variant on the disease risk. Here, we addressed this question by examining the genetic effects for 43 validated gene-disease associations across 697 study populations of various descents. The frequencies of the genetic marker of interest in the control populations often (58%) showed large heterogeneity (statistical variability) between 'races'. Conversely, we saw large heterogeneity in the genetic effects (odds ratios) between 'races' in only 14% of cases. Genetic markers for proposed gene-disease associations vary in frequency across populations, but their biological impact on the risk for common diseases may usually be consistent across traditional 'racial' boundaries.
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| The CHRNA5-CHRNA3-CHRNB4 nicotinic receptor subunit gene cluster affects risk for nicotine dependence in African-Americans and in European-Americans. | Saccone NL et al. | β | 2009 | β |
| The common apolipoprotein A-1 polymorphism -75A>G is associated with ethnic differences in recurrent coronary events after recovery from an acute myocardial infarction. | Block R et al. | β | 2009 | β |
| Validating, augmenting and refining genome-wide association signals. | Ioannidis JP et al. | β | 2009 | β |
| Vilazodone, a novel, dual-acting antidepressant: current status, future promise and potential for individualized treatment of depression. | Rickels K et al. | β | 2009 | β |
| What causes racial disparities in very preterm birth? A biosocial perspective. | Kramer MR et al. | β | 2009 | β |
| CASP8 variants D302H and -652 6N ins/del do not influence the risk of colorectal cancer in the United Kingdom population. | Pittman AM et al. | β | 2008 | β |
| Cumulative burden of atherosclerotic risk genotypes and the age at onset of a first myocardial infarction: a case-only carriership approach. | Goldenberg I et al. | β | 2008 | β |
| Evaluation of genetic variation contributing to differences in gene expression between populations. | Zhang W et al. | β | 2008 | β |
| Family-based association study of the MTHFR polymorphism C677T in patients with nonsyndromic cleft lip and palate from central Europe. | Reutter H et al. | β | 2008 | β |
| Genetic variants of Y chromosome are associated with a protective lipid profile in black men. | Russo P et al. | β | 2008 | β |
| Human leukocyte antigen class II associations with hepatitis C virus clearance and virus-specific CD4 T cell response among Caucasians and African Americans. | Harris RA et al. | β | 2008 | β |
| In search of causal variants: refining disease association signals using cross-population contrasts. | Saccone NL et al. | β | 2008 | β |
| Interferon regulatory factor-5 is genetically associated with systemic lupus erythematosus in African Americans. | Kelly JA et al. | β | 2008 | β |
| Interleukin-12 receptor beta1 polymorphisms and nontuberculous mycobacterial lung diseases. | Park HY et al. | β | 2008 | β |
| Lack of association between variants in the VKORC1 gene and cerebrovascular or coronary heart disease. | Lemmens R et al. | β | 2008 | β |
| Meta-analysis methods. | Trikalinos TA et al. | β | 2008 | β |
| No association between common chemokine and chemokine receptor gene variants and prostate cancer risk. | Petersen DC et al. | β | 2008 | β |
| Regulatory polymorphisms in the interleukin-18 promoter are associated with hepatitis C virus clearance. | An P et al. | β | 2008 | β |
| Required sample size and nonreplicability thresholds for heterogeneous genetic associations. | Moonesinghe R et al. | β | 2008 | β |
| Study designs for genome-wide association studies. | Kraft P et al. | β | 2008 | β |
| Synthesis of genetic association studies for pertinent gene-disease associations requires appropriate methodological and statistical approaches. | Zintzaras E et al. | β | 2008 | β |
| Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database. | Allen NC et al. | β | 2008 | β |
| The association of genetic variants in KrΓΌppel-like factor 11 and Type 2 diabetes in the Japanese population. | Tanahashi T et al. | β | 2008 | β |
| The HapMap Resource is Providing New Insights into Ourselves and its Application to Pharmacogenomics. | Zhang W et al. | β | 2008 | β |
| The Mediterranean paradox for susceptibility factors in coronary heart disease extends to genetics. | Lao O et al. | β | 2008 | β |
| Tilting at quixotic trait loci (QTL): an evolutionary perspective on genetic causation. | Weiss KM | β | 2008 | β |
| Tumour-necrosis factor-A polymorphisms and gastric cancer risk: a meta-analysis. | Gorouhi F et al. | β | 2008 | β |
| Worldwide population differentiation at disease-associated SNPs. | Myles S et al. | β | 2008 | β |
| A comprehensive analysis of common genetic variation in prolactin (PRL) and PRL receptor (PRLR) genes in relation to plasma prolactin levels and breast cancer risk: the multiethnic cohort. | Lee SA et al. | β | 2007 | β |
| A multicenter study of BRD2 as a risk factor for juvenile myoclonic epilepsy. | Cavalleri GL et al. | β | 2007 | β |
| A NOS1 gene polymorphism associated with asthma and specific immunoglobulin E response to mite allergens in a Colombian population. | MartΓnez B et al. | β | 2007 | β |
| Association of the C-344T aldosterone synthase gene variant with essential hypertension: a meta-analysis. | Sookoian S et al. | β | 2007 | β |
| Bayesian meta-analysis and meta-regression for gene-disease associations and deviations from Hardy-Weinberg equilibrium. | Salanti G et al. | β | 2007 | β |
| Comments on the paper by D. Li and L. He: meta-analysis shows association between the tryptophan hydroxylase (TPH) gene and schizophrenia. | Sand PG | β | 2007 | β |
| Comprehensive linkage and linkage heterogeneity analysis of 4344 sibling pairs affected with hypertension from the Family Blood Pressure Program. | Greenwood TA et al. | β | 2007 | β |
| Current status of genome-wide scanning for hypertension. | Hamet P et al. | β | 2007 | β |
| Effect of genetic variants of CCR2 and CCL2 on the natural history of HIV-1 infection: CCL2-2518GG is overrepresented in a cohort of Spanish HIV-1-infected subjects. | ViladΓ©s C et al. | β | 2007 | β |
| Genetic epistasis in the VLDL catabolic pathway is associated with deleterious variations on triglyceridemia in obese subjects. | Brisson D et al. | β | 2007 | β |
| Genetics of asthma: potential implications for reducing asthma disparities. | Scirica CV et al. | β | 2007 | β |
| Genetics of ischaemic stroke among persons of non-European descent: a meta-analysis of eight genes involving approximately 32,500 individuals. | Ariyaratnam R et al. | β | 2007 | β |
| Genetic variation and human aging: progress and prospects. | Melzer D et al. | β | 2007 | β |
| Maternal gene polymorphisms involved in folate metabolism and risk of Down syndrome offspring: a meta-analysis. | Zintzaras E | β | 2007 | β |
| Medicine, genetics and race: the case of cardiovascular diseases. | Ordovas JM | β | 2007 | β |
| New developments in the search for genetic determinants of osteoarthritis. | Ralston SH | β | 2007 | β |
| No association of polymorphisms in the gene encoding 5-lipoxygenase-activating protein and myocardial infarction in a large central European population. | Koch W et al. | β | 2007 | β |
| Patterns of population differentiation of candidate genes for cardiovascular disease. | Kullo IJ et al. | β | 2007 | β |
| Polymorphisms in the KDR and POSTN genes: association with breast cancer susceptibility and prognosis. | FΓΆrsti A et al. | β | 2007 | β |
| Race and ethnicity in genetic research. | Sankar P et al. | β | 2007 | β |
| Race, genetics and medicine: does the color of a leopard's spots matter? | Bamshad M et al. | β | 2007 | β |
| Replicating genome-wide association studies. | Kuniholm MH | β | 2007 | β |
| [Studies of association in complex diseases: statistical problems related to the analysis of genetic polymorphisms]. | Salas A et al. | β | 2007 | β |
| Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database. | Bertram L et al. | β | 2007 | β |
| The structure of common genetic variation in United States populations. | Guthery SL et al. | β | 2007 | β |
| Association between polymorphism of tumour necrosis factor alpha-308 gene promoter and asthma: a meta-analysis. | Gao J et al. | β | 2006 | β |
| Association of estrogen receptor alpha gene polymorphisms with bone mineral density in postmenopausal Indian women. | Mitra S et al. | β | 2006 | β |
| Association of methylenetetrahydrofolate reductase (MTHFR) polymorphisms with genetic susceptibility to gastric cancer: a meta-analysis. | Zintzaras E | β | 2006 | β |
| Association of Phosphodiesterase 4D with ischemic stroke: a population-based case-control study. | Woo D et al. | β | 2006 | β |
| Associations among race/ethnicity, ApoC-III genotypes, and lipids in HIV-1-infected individuals on antiretroviral therapy. | Foulkes AS et al. | β | 2006 | β |
| Asthma in Hispanics. | Hunninghake GM et al. | β | 2006 | β |
| A systematic assessment of common genetic variation in CYP11A and risk of breast cancer. | Setiawan VW et al. | β | 2006 | β |
| Common genetic variation in five thrombosis genes and relations to plasma hemostatic protein level and cardiovascular disease risk. | Kathiresan S et al. | β | 2006 | β |
| Concordance of functional in vitro data and epidemiological associations in complex disease genetics. | Ioannidis JP et al. | β | 2006 | β |
| Confronting ethnicity-specific disease risk. | Tang H | β | 2006 | β |
| Cytokine gene polymorphisms and atopic disease in two European cohorts. (ECRHS-Basel and SAPALDIA). | Imboden M et al. | β | 2006 | β |
| Dissecting complex disease: the quest for the Philosopher's Stone? | Buchanan AV et al. | β | 2006 | β |
| Do alcohol-metabolizing enzyme gene polymorphisms increase the risk of alcoholism and alcoholic liver disease? | Zintzaras E et al. | β | 2006 | β |
| Endothelial nitric oxide synthase gene polymorphisms and cardiovascular disease: a HuGE review. | Casas JP et al. | β | 2006 | β |
| Endothelial NO synthase gene polymorphisms and hypertension: a meta-analysis. | Zintzaras E et al. | β | 2006 | β |
| Factor XIII Val34Leu variant is protective against venous thromboembolism: a HuGE review and meta-analysis. | Wells PS et al. | β | 2006 | β |
| Gene-based single nucleotide polymorphisms and linkage disequilibrium patterns of 29 asthma candidate genes in the chromosome 5q31-33 region in Koreans. | Ryu HJ et al. | β | 2006 | β |
| Genetic association studies in cancer: good, bad or no longer ugly? | Savage SA et al. | β | 2006 | β |
| Genetic dissection of the common epilepsies. | Tan NC et al. | β | 2006 | β |
| Genetic, ethnic, and gender differences in the pharmacokinetics of antiretroviral agents. | Rotger M et al. | β | 2006 | β |
| Genetic polymorphisms in base-excision repair pathway genes and risk of breast cancer. | Zhang Y et al. | β | 2006 | β |
| Genetics of osteoporosis. | Huang QY et al. | β | 2006 | β |
| Geographic ancestry, angiotensinogen gene polymorphism, and cardiovascular risk. | Castellano M | β | 2006 | β |
| Hispanic drug abuse research: challenges and opportunities. | Volkow ND | β | 2006 | β |
| Impact of violations and deviations in Hardy-Weinberg equilibrium on postulated gene-disease associations. | Trikalinos TA et al. | β | 2006 | β |
| Impaired collagen chaperone results in preterm PROM. | Taylor KH et al. | β | 2006 | β |
| Implications of small effect sizes of individual genetic variants on the design and interpretation of genetic association studies of complex diseases. | Ioannidis JP et al. | β | 2006 | β |
| Interaction between serotonin 2A receptor and endothelin-1 variants in association with hypertension in Japanese. | Yamamoto M et al. | β | 2006 | β |
| Interleukin-1B polymorphisms and gastric cancer risk--a meta-analysis. | Kamangar F et al. | β | 2006 | β |
| Lack of genetic association between the phospholipase A2 gene and bipolar mood disorder in a European multicentre case-control study. | Dikeos DG et al. | β | 2006 | β |
| Meta-analysis of TNF-alpha promoter -308 A/G polymorphism and SLE susceptibility. | Lee YH et al. | β | 2006 | β |
| Methylenetetrahydrofolate reductase gene and susceptibility to breast cancer: a meta-analysis. | Zintzaras E | β | 2006 | β |
| Patterns of association between PPARgamma genetic variation and indices of adiposity and insulin action in African-Americans and whites: the CARDIA Study. | Wei Q et al. | β | 2006 | β |
| PDE4D and stroke: a real advance or a case of the Emperor's new clothes? | Worrall BB et al. | β | 2006 | β |
| Race and ethnicity in the era of emerging pharmacogenomics. | Harty L et al. | β | 2006 | β |
| Sex steroid hormone gene polymorphisms and depressive symptoms in women at midlife. | Kravitz HM et al. | β | 2006 | β |
| Social disadvantage and cardiovascular disease: development of an index and analysis of age, sex, and ethnicity effects. | Anand SS et al. | β | 2006 | β |
| The beta2-adrenoceptor gene and hypertension: is it the promoter or the coding region or neither? | Hahntow IN et al. | β | 2006 | β |
| The CALM1 core promoter polymorphism is not associated with hip osteoarthritis in a United Kingdom Caucasian population. | Loughlin J et al. | β | 2006 | β |
| The Genetic Basis of Type 2 Diabetes. | Das SK et al. | β | 2006 | β |
| The L513S polymorphism in medium-chain acyl-CoA synthetase 2 (MACS2) is associated with risk factors of the metabolic syndrome in a Caucasian study population. | Lindner I et al. | β | 2006 | β |
| Timely translation of ophthalmic research into clinical practice. | McCarty CA | β | 2006 | β |
| Updating the East Asian mtDNA phylogeny: a prerequisite for the identification of pathogenic mutations. | Kong QP et al. | β | 2006 | β |
| Vitamin D receptor gene polymorphisms and bone mineral density in postmenopausal Indian women. | Mitra S et al. | β | 2006 | β |
| Association of the CTLA-4 gene with rheumatoid arthritis in Chinese Han population. | Lei C et al. | β | 2005 | β |
| Common variation in EMSY and risk of breast and ovarian cancer: a case-control study using HapMap tagging SNPs. | Benusiglio PR et al. | β | 2005 | β |
| CTLA-4 gene polymorphisms and susceptibility to type 1 diabetes mellitus: a HuGE Review and meta-analysis. | Kavvoura FK et al. | β | 2005 | β |
| Ethnic differences in allele frequency of autoimmune-disease-associated SNPs. | Mori M et al. | β | 2005 | β |
| Failure to replicate previously reported genetic associations with sporadic temporal lobe epilepsy: where to from here? | Cavalleri GL et al. | β | 2005 | β |
| Genetics of leptin and obesity: a HuGE review. | Paracchini V et al. | β | 2005 | β |
| Geography is a better determinant of human genetic differentiation than ethnicity. | Manica A et al. | β | 2005 | β |
| Hardy-Weinberg equilibrium in genetic association studies: an empirical evaluation of reporting, deviations, and power. | Salanti G et al. | β | 2005 | β |
| Investigating the aspartic acid (D) repeat of asporin as a risk factor for osteoarthritis in a UK Caucasian population. | Mustafa Z et al. | β | 2005 | β |
| Local literature bias in genetic epidemiology: an empirical evaluation of the Chinese literature. | Pan Z et al. | β | 2005 | β |
| Meta-analysis of the association of beta2-adrenergic receptor polymorphisms with asthma phenotypes. | Contopoulos-Ioannidis DG et al. | β | 2005 | β |
| Meta-analysis on the G-308A tumor necrosis factor alpha gene variant and phenotypes associated with the metabolic syndrome. | Sookoian SC et al. | β | 2005 | β |
| Pharmacogenetics and geographical ancestry: implications for drug development and global health. | Daar AS et al. | β | 2005 | β |
| Replication of an Egfr-wing shape association in a wild-caught cohort of Drosophila melanogaster. | Dworkin I et al. | β | 2005 | β |
| Replication of putative candidate-gene associations with rheumatoid arthritis in >4,000 samples from North America and Sweden: association of susceptibility with PTPN22, CTLA4, and PADI4. | Plenge RM et al. | β | 2005 | β |
| Risk for HIV-1 infection associated with a common CXCL12 (SDF1) polymorphism and CXCR4 variation in an African population. | Petersen DC et al. | β | 2005 | β |
| Susceptibility genes for complex epilepsy. | Mulley JC et al. | β | 2005 | β |
| Tests for the replication of an association between Egfr and natural variation in Drosophila melanogaster wing morphology. | Palsson A et al. | β | 2005 | β |
| The relationship between C677T methylenetetrahydrofolate reductase gene polymorphism and retinopathy in type 2 diabetes: a meta-analysis. | Zintzaras E et al. | β | 2005 | β |
| The role of G196A polymorphism in the brain-derived neurotrophic factor gene in the cause of Parkinson's disease: a meta-analysis. | Zintzaras E et al. | β | 2005 | β |
| The Swedish family-cancer database: update, application to colorectal cancer and clinical relevance. | Hemminki K et al. | β | 2005 | β |
| In genetic control of disease, does 'race' matter? | Goldstein DB et al. | β | 2004 | β |