Center for Research on Genomics and Global Health

Bethesda, MD, United States

Center for Research on Genomics and Global Health

Bethesda, MD, United States
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Iyengar S.K.,Case Western Reserve University | Sedor J.R.,Case Western Reserve University | Freedman B.I.,Section on Nephrology | Kao W.H.L.,University of Baltimore | And 52 more authors.
PLoS Genetics | Year: 2015

Diabetic kidney disease (DKD) is the most common etiology of chronic kidney disease (CKD) in the industrialized world and accounts for much of the excess mortality in patients with diabetes mellitus. Approximately 45% of U.S. patients with incident end-stage kidney disease (ESKD) have DKD. Independent of glycemic control, DKD aggregates in families and has higher incidence rates in African, Mexican, and American Indian ancestral groups relative to European populations. The Family Investigation of Nephropathy and Diabetes (FIND) performed a genome-wide association study (GWAS) contrasting 6,197 unrelated individuals with advanced DKD with healthy and diabetic individuals lacking nephropathy of European American, African American, Mexican American, or American Indian ancestry. A large-scale replication and trans-ethnic meta-analysis included 7,539 additional European American, African American and American Indian DKD cases and non-nephropathy controls. Within ethnic group meta-analysis of discovery GWAS and replication set results identified genome-wide significant evidence for association between DKD and rs12523822 on chromosome 6q25.2 in American Indians (P = 5.74x10-9). The strongest signal of association in the trans-ethnic meta-analysis was with a SNP in strong linkage disequilibrium with rs12523822 (rs955333; P = 1.31x10-8), with directionally consistent results across ethnic groups. These 6q25.2 SNPs are located between the SCAF8 and CNKSR3 genes, a region with DKD relevant changes in gene expression and an eQTL with IPCEF1, a gene co-translated with CNKSR3. Several other SNPs demonstrated suggestive evidence of association with DKD, within and across populations. These data identify a novel DKD susceptibility locus with consistent directions of effect across diverse ancestral groups and provide insight into the genetic architecture of DKD.


de Vries J.,University of Cape Town | Tindana P.,Navrongo Health Research Center | Littler K.,Wellcome Trust Sanger Institute | Ramsay M.,University of Witwatersrand | And 4 more authors.
Trends in Genetics | Year: 2015

Human Heredity and Health in Africa (H3Africa) research seeks to promote fair collaboration between scientists in Africa and those from elsewhere. Here, we outline how concerns over inequality and exploitation led to a policy framework that places a firm focus on African leadership and capacity building as guiding principles for African genomics research. © 2015 The Authors.


Chen G.,Center for Research on Genomics and Global Health | Bentley A.,Center for Research on Genomics and Global Health | Adeyemo A.,Center for Research on Genomics and Global Health | Shriner D.,Center for Research on Genomics and Global Health | And 9 more authors.
Human Molecular Genetics | Year: 2012

Insulin resistance (IR) is a key determinant of type 2 diabetes (T2D) and other metabolic disorders. This genome-wide association study (GWAS) was designed to shed light on the genetic basis of fasting insulin (FI) and IR in 927 non-diabetic African Americans. 5 396 838 single-nucleotide polymorphisms (SNPs) were tested for associations with FI or IR with adjustments for age, sex, body mass index, hypertension status and first two principal components. Genotyped SNPs (n = 12) with P < 5 × 10-6 in African Americans were carried forward for de novo genotyping in 570 non-diabetic West Africans. We replicated SNPs in or near SC4MOL and TCERG1L in West Africans. The meta-analysis of 1497 African Americans and West Africans yielded genome-wide significant associations for SNPs in the SC4MOL gene: rs17046216 (P = 1.7 × 10-8 and 2.9 × 10-8 for FI and IR, respectively); and near the TCERG1L gene with rs7077836 as the top scoring (P = 7.5 × 10-9 and 4.9 × 10-10 for FI and IR, respectively). In silico replication in the MAGIC study (n = 37 037) showed weak but significant association (adjusted P-value of 0.0097) for rs34602777 in the MYO5A gene. In addition, we replicated previous GWAS findings for IR and FI in Europeans for GCKR, and for variants in four T2D loci (FTO, IRS1, KLF14 and PPARG) which exert their action via IR. In summary, variants in/near SC4MOL, and TCERG1L were associated with FI and IR in this cohort of African Americans and were replicated in West Africans. SC4MOL is under-expressed in an animal model of T2D and plays a key role in lipid biosynthesis, with implications for the regulation of energy metabolism, obesity and dyslipidemia. TCERG1L is associated with plasma adiponectin, a key modulator of obesity, inflammation, IR and diabetes. © The Author 2012. Published by Oxford University Press. All rights reserved.


PubMed | University of California at Irvine, Urologic, Harvard University, U.S. National Cancer Institute and 23 more.
Type: Journal Article | Journal: PLoS genetics | Year: 2015

Diabetic kidney disease (DKD) is the most common etiology of chronic kidney disease (CKD) in the industrialized world and accounts for much of the excess mortality in patients with diabetes mellitus. Approximately 45% of U.S. patients with incident end-stage kidney disease (ESKD) have DKD. Independent of glycemic control, DKD aggregates in families and has higher incidence rates in African, Mexican, and American Indian ancestral groups relative to European populations. The Family Investigation of Nephropathy and Diabetes (FIND) performed a genome-wide association study (GWAS) contrasting 6,197 unrelated individuals with advanced DKD with healthy and diabetic individuals lacking nephropathy of European American, African American, Mexican American, or American Indian ancestry. A large-scale replication and trans-ethnic meta-analysis included 7,539 additional European American, African American and American Indian DKD cases and non-nephropathy controls. Within ethnic group meta-analysis of discovery GWAS and replication set results identified genome-wide significant evidence for association between DKD and rs12523822 on chromosome 6q25.2 in American Indians (P = 5.74x10-9). The strongest signal of association in the trans-ethnic meta-analysis was with a SNP in strong linkage disequilibrium with rs12523822 (rs955333; P = 1.31x10-8), with directionally consistent results across ethnic groups. These 6q25.2 SNPs are located between the SCAF8 and CNKSR3 genes, a region with DKD relevant changes in gene expression and an eQTL with IPCEF1, a gene co-translated with CNKSR3. Several other SNPs demonstrated suggestive evidence of association with DKD, within and across populations. These data identify a novel DKD susceptibility locus with consistent directions of effect across diverse ancestral groups and provide insight into the genetic architecture of DKD.


News Article | October 25, 2016
Site: www.technologyreview.com

An overwhelming majority of the data collected is from people of European ancestry. But researchers are trying to change that. When geneticist Kent Taylor of the Los Angeles Biomedical Research Institute set out two years ago to write a grant to study genetic risk factors for type 2 diabetes in Hispanics, he couldn’t find much research. He consulted an international collection of all published genome-wide association studies, called the GWAS Catalog, and found 19 studies on type 2 diabetes in Europeans, 14 in Asians, three in Hispanics, one in Mexicans, and one in an American Indian population in Arizona. These genome-wide association studies scan the DNA of many people to spot genetic variants associated with drivers of disease. But large population groups—including Africans, Latin Americans, and native or indigenous people—are hugely underrepresented in these studies and genomics research in general. Without this information, researchers may be missing key genetic factors that play a role in disease susceptibility and drug response among different population groups. Taylor says the GWAS Catalog is the most important tool in modern genetics, but we’re “not even close” to completing it. He says more genomic diversity is needed to establish a “basic genome infrastructure” that researchers can use to study disease across different populations. A recent analysis published in the journal Nature revealed that 81 percent of participants in these genome-wide association studies were of European descent. Together, individuals of African, Latin American, and native or indigenous ancestry represent less than 4 percent of all genomic samples analyzed. While the overall diversity in genome-wide association studies has increased since 2009, when 96 percent of data was from people of European descent, much of the rise in diversity is due to large gains in Asian data and only marginal increases from other population groups. Adebowale Adeyemo, deputy director of the Center for Research on Genomics and Global Health at the National Human Genome Research Institute (part of the National Institutes of Health), says the research community has tended to assume that poorer countries, like many in Africa, Asia, and Central and South America, don’t need genomic studies because the biggest killers there are infectious diseases. But chronic diseases, like diabetes and heart disease, are now on the rise in lower-income countries too, and Adeyemo says more genome studies are needed to understand different populations’ risk factors for these conditions. An international group of researchers known as the Human Heredity and Health in Africa Initiative, or H3Africa, is trying to increase what researchers know about genetics in African populations. The project, which consists of 14 studies looking at different diseases, is collecting data from genome-wide association studies as well as genome sequencing data—the entire readout of a person’s DNA—from thousands of participants. Another effort to increase diversity in genomics research is the Hispanic Community Health Study/Study of Latinos launched by the National Institutes of Health (NIH) in 2013. The study, which will include 16,000 participants, is meant to establish the risk factors for cardiovascular and pulmonary disease and chronic diseases in Latin Americans. But Taylor says there is so much genetic diversity among Hispanics and people from Latin America that additional studies will need to be done. NIH is also in the midst of a 30-year-long study on American Indian men and women and their genetic risk factors for cardiovascular disease. Companies like Illumina and 23andMe are developing new tools to help researchers like these explore genetic variations in different population groups. Illumina is partnering with H3Africa to develop a microarray—a laboratory test chip used to determine differences in genetic makeup within a population—that contains information from more people of African descent than any other commercially available array. The array will include 2.5 million genetic variations that appear in African populations. The information comes from genomic samples of 3,000 individuals collected by H3Africa. That represents much more genetic diversity than Illumina’s current tests, which include genetic information from fewer than 700 Africans. Last year, Illumina made available a new array for populations of diverse ancestries. Julie Collens, Illumina’s senior manager for market development, says a chip for Africans was needed because the region is so genetically diverse, and previous arrays included only a small sampling of genetic information from Africa. Illumina has 28 chips commercially available to use for human genetic studies, including those for specific diseases like immune disorders and psychiatric diseases, as well as a Chinese population array. In addition, 23andMe has announced that it is building a reference database containing the whole genome sequences of the company’s African-American customers who have consented to participate in research. Adam Auton, a 23andMe senior scientist and statistical geneticist, says the company is aiming to include sequences from more than 900 people in the database, which will eventually be shared with NIH and available for researchers. To date, most whole genome sequences have been done in people of European descent. While Adeyemo says these new tools will certainly be helpful, their introduction doesn’t represent as big a shift in genomics research as he would like. Researchers have to want to do research in non-European populations, he says—and scientific organizations around the world have to provide funding to support those kinds of studies.

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