Multi-ancestry GWAS analysis identifies two novel loci associated with diabetic eye disease and highlights APOL1 as a high risk locus in patients with diabetic macular edema
Diabetic retinopathy (DR) is a common complication of diabetes. Approximately 20% of DR patients have diabetic macular edema (DME) characterized by fluid leakage into the retina. There is a genetic component to DR and DME risk, but few replicable loci. Because not all DR cases have DME, we focused o...
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| Veröffentlicht in: | PLoS genetics 2023-08, Vol.19 (8), p.e1010609-e1010609 |
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| creator | Stockwell, Amy D Chang, Michael C Mahajan, Anubha Forrest, William Anegondi, Neha Pendergrass, Rion K Selvaraj, Suresh Reeder, Jens Wei, Eric Iglesias, Victor A Creps, Natalie M Macri, Laura Neeranjan, Andrea N van der Brug, Marcel P Scales, Suzie J McCarthy, Mark I Yaspan, Brian L |
| description | Diabetic retinopathy (DR) is a common complication of diabetes. Approximately 20% of DR patients have diabetic macular edema (DME) characterized by fluid leakage into the retina. There is a genetic component to DR and DME risk, but few replicable loci. Because not all DR cases have DME, we focused on DME to increase power, and conducted a multi-ancestry GWAS to assess DME risk in a total of 1,502 DME patients and 5,603 non-DME controls in discovery and replication datasets. Two loci reached GWAS significance (p |
| doi_str_mv | 10.1371/journal.pgen.1010609 |
| format | Article |
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Approximately 20% of DR patients have diabetic macular edema (DME) characterized by fluid leakage into the retina. There is a genetic component to DR and DME risk, but few replicable loci. Because not all DR cases have DME, we focused on DME to increase power, and conducted a multi-ancestry GWAS to assess DME risk in a total of 1,502 DME patients and 5,603 non-DME controls in discovery and replication datasets. Two loci reached GWAS significance (p<5x10.sup.-8). The strongest association was rs2239785, (K150E) in APOL1. The second finding was rs10402468, which co-localized to PLVAP and ANKLE1 in vascular / endothelium tissues. We conducted multiple sensitivity analyses to establish that the associations were specific to DME status and did not reflect diabetes status or other diabetic complications. Here we report two novel loci for risk of DME which replicated in multiple clinical trial and biobank derived datasets. One of these loci, containing the gene APOL1, is a risk factor in African American DME and DKD patients, indicating that this locus plays a broader role in diabetic complications for multiple ancestries.</description><identifier>ISSN: 1553-7404</identifier><identifier>ISSN: 1553-7390</identifier><identifier>EISSN: 1553-7404</identifier><identifier>DOI: 10.1371/journal.pgen.1010609</identifier><identifier>PMID: 37585454</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>African Americans ; Asthma ; Biology and Life Sciences ; Biotechnology industry ; Care and treatment ; Clinical trials ; Diabetes ; Diabetes mellitus ; Diabetic retinopathy ; Dropsy ; Drug dosages ; Edema ; Endothelium ; Eye diseases ; Genetic aspects ; Genetic testing ; Genome-wide association studies ; Genomes ; Genotype & phenotype ; Health risk assessment ; Identification and classification ; Medicine and Health Sciences ; Patients ; People and Places ; Quality control ; Quantitative trait loci ; Retinopathy ; Risk factors ; Sensitivity analysis ; Software</subject><ispartof>PLoS genetics, 2023-08, Vol.19 (8), p.e1010609-e1010609</ispartof><rights>COPYRIGHT 2023 Public Library of Science</rights><rights>2023 Stockwell et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 Stockwell et al 2023 Stockwell et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c704t-a667eb46da8c68e97c7fb20600a2e646398c44ec8ea3905c5fd4436ac2e6af8f3</citedby><cites>FETCH-LOGICAL-c704t-a667eb46da8c68e97c7fb20600a2e646398c44ec8ea3905c5fd4436ac2e6af8f3</cites><orcidid>0000-0002-3787-2510 ; 0000-0003-3063-6723 ; 0000-0003-2544-0283</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10461827/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10461827/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids></links><search><contributor>Barsh, Gregory S.</contributor><creatorcontrib>Stockwell, Amy D</creatorcontrib><creatorcontrib>Chang, Michael C</creatorcontrib><creatorcontrib>Mahajan, Anubha</creatorcontrib><creatorcontrib>Forrest, William</creatorcontrib><creatorcontrib>Anegondi, Neha</creatorcontrib><creatorcontrib>Pendergrass, Rion K</creatorcontrib><creatorcontrib>Selvaraj, Suresh</creatorcontrib><creatorcontrib>Reeder, Jens</creatorcontrib><creatorcontrib>Wei, Eric</creatorcontrib><creatorcontrib>Iglesias, Victor A</creatorcontrib><creatorcontrib>Creps, Natalie M</creatorcontrib><creatorcontrib>Macri, Laura</creatorcontrib><creatorcontrib>Neeranjan, Andrea N</creatorcontrib><creatorcontrib>van der Brug, Marcel P</creatorcontrib><creatorcontrib>Scales, Suzie J</creatorcontrib><creatorcontrib>McCarthy, Mark I</creatorcontrib><creatorcontrib>Yaspan, Brian L</creatorcontrib><title>Multi-ancestry GWAS analysis identifies two novel loci associated with diabetic eye disease and highlights APOL1 as a high risk locus in patients with diabetic macular edema</title><title>PLoS genetics</title><description>Diabetic retinopathy (DR) is a common complication of diabetes. Approximately 20% of DR patients have diabetic macular edema (DME) characterized by fluid leakage into the retina. There is a genetic component to DR and DME risk, but few replicable loci. Because not all DR cases have DME, we focused on DME to increase power, and conducted a multi-ancestry GWAS to assess DME risk in a total of 1,502 DME patients and 5,603 non-DME controls in discovery and replication datasets. Two loci reached GWAS significance (p<5x10.sup.-8). The strongest association was rs2239785, (K150E) in APOL1. The second finding was rs10402468, which co-localized to PLVAP and ANKLE1 in vascular / endothelium tissues. We conducted multiple sensitivity analyses to establish that the associations were specific to DME status and did not reflect diabetes status or other diabetic complications. Here we report two novel loci for risk of DME which replicated in multiple clinical trial and biobank derived datasets. One of these loci, containing the gene APOL1, is a risk factor in African American DME and DKD patients, indicating that this locus plays a broader role in diabetic complications for multiple ancestries.</description><subject>African Americans</subject><subject>Asthma</subject><subject>Biology and Life Sciences</subject><subject>Biotechnology industry</subject><subject>Care and treatment</subject><subject>Clinical trials</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetic retinopathy</subject><subject>Dropsy</subject><subject>Drug dosages</subject><subject>Edema</subject><subject>Endothelium</subject><subject>Eye diseases</subject><subject>Genetic aspects</subject><subject>Genetic testing</subject><subject>Genome-wide association studies</subject><subject>Genomes</subject><subject>Genotype & phenotype</subject><subject>Health risk assessment</subject><subject>Identification and classification</subject><subject>Medicine and Health 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GWAS analysis identifies two novel loci associated with diabetic eye disease and highlights APOL1 as a high risk locus in patients with diabetic macular edema</title><author>Stockwell, Amy D ; Chang, Michael C ; Mahajan, Anubha ; Forrest, William ; Anegondi, Neha ; Pendergrass, Rion K ; Selvaraj, Suresh ; Reeder, Jens ; Wei, Eric ; Iglesias, Victor A ; Creps, Natalie M ; Macri, Laura ; Neeranjan, Andrea N ; van der Brug, Marcel P ; Scales, Suzie J ; McCarthy, Mark I ; Yaspan, Brian L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c704t-a667eb46da8c68e97c7fb20600a2e646398c44ec8ea3905c5fd4436ac2e6af8f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>African Americans</topic><topic>Asthma</topic><topic>Biology and Life Sciences</topic><topic>Biotechnology industry</topic><topic>Care and treatment</topic><topic>Clinical trials</topic><topic>Diabetes</topic><topic>Diabetes 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two novel loci associated with diabetic eye disease and highlights APOL1 as a high risk locus in patients with diabetic macular edema</atitle><jtitle>PLoS genetics</jtitle><date>2023-08-16</date><risdate>2023</risdate><volume>19</volume><issue>8</issue><spage>e1010609</spage><epage>e1010609</epage><pages>e1010609-e1010609</pages><issn>1553-7404</issn><issn>1553-7390</issn><eissn>1553-7404</eissn><abstract>Diabetic retinopathy (DR) is a common complication of diabetes. Approximately 20% of DR patients have diabetic macular edema (DME) characterized by fluid leakage into the retina. There is a genetic component to DR and DME risk, but few replicable loci. Because not all DR cases have DME, we focused on DME to increase power, and conducted a multi-ancestry GWAS to assess DME risk in a total of 1,502 DME patients and 5,603 non-DME controls in discovery and replication datasets. Two loci reached GWAS significance (p<5x10.sup.-8). The strongest association was rs2239785, (K150E) in APOL1. The second finding was rs10402468, which co-localized to PLVAP and ANKLE1 in vascular / endothelium tissues. We conducted multiple sensitivity analyses to establish that the associations were specific to DME status and did not reflect diabetes status or other diabetic complications. Here we report two novel loci for risk of DME which replicated in multiple clinical trial and biobank derived datasets. One of these loci, containing the gene APOL1, is a risk factor in African American DME and DKD patients, indicating that this locus plays a broader role in diabetic complications for multiple ancestries.</abstract><cop>San Francisco</cop><pub>Public Library of Science</pub><pmid>37585454</pmid><doi>10.1371/journal.pgen.1010609</doi><tpages>e1010609</tpages><orcidid>https://orcid.org/0000-0002-3787-2510</orcidid><orcidid>https://orcid.org/0000-0003-3063-6723</orcidid><orcidid>https://orcid.org/0000-0003-2544-0283</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | African Americans Asthma Biology and Life Sciences Biotechnology industry Care and treatment Clinical trials Diabetes Diabetes mellitus Diabetic retinopathy Dropsy Drug dosages Edema Endothelium Eye diseases Genetic aspects Genetic testing Genome-wide association studies Genomes Genotype & phenotype Health risk assessment Identification and classification Medicine and Health Sciences Patients People and Places Quality control Quantitative trait loci Retinopathy Risk factors Sensitivity analysis Software |
| title | Multi-ancestry GWAS analysis identifies two novel loci associated with diabetic eye disease and highlights APOL1 as a high risk locus in patients with diabetic macular edema |
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