A replication study of 49 Type 2 diabetes risk variants in a Punjabi Pakistani population
Aim The burden of Type 2 diabetes is alarmingly high in South Asia, a region that has many genetically diverse ethnic populations. Genome‐wide association studies (GWAS) conducted largely in European populations have identified a number of loci predisposing to Type 2 diabetes risk, however, the rele...
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| Veröffentlicht in: | Diabetic medicine 2016-08, Vol.33 (8), p.1112-1117 |
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| container_title | Diabetic medicine |
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| creator | Zia, A. Wang, X. Bhatti, A. Demirci, F. Y. Zhao, W. Rasheed, A. Samuel, M. Kiani, A. K. Ismail, M. Zafar, J. John, P. Saleheen, D. Kamboh, M. I. |
| description | Aim
The burden of Type 2 diabetes is alarmingly high in South Asia, a region that has many genetically diverse ethnic populations. Genome‐wide association studies (GWAS) conducted largely in European populations have identified a number of loci predisposing to Type 2 diabetes risk, however, the relevance of such genetic loci in many South Asian sub‐ethnicities remains elusive. The aim of this study was to replicate 49 single nucleotide polymorphisms (SNPs) previously identified through GWAS in Punjabis living in Pakistan.
Methods
We examined the association of 49 SNPs in 853 Type 2 diabetes cases and 1945 controls using additive logistic regression models after adjusting for age and gender.
Results
Of the 49 SNPs investigated, eight showed a nominal association (P < 0.05) that also remained significant after controlling for the false discovery rate. The most significant association was found for rs7903146 at the TCF7L2 locus. For a per unit increase in the risk score comprising of all the 49 SNPs, the odds ratio in association with Type 2 diabetes risk was 1.16 (95% CI 1.13–1.19, P < 2.0E–16).
Conclusion
These results suggest that some Type 2 diabetes susceptibility loci are shared between Europeans and Punjabis living in Pakistan.
What's new?
There have been limited studies on the genetic basis of Type 2 diabetes in the Pakistani population.
This study aimed to replicate 49 genome‐wide association studies significant single nucleotide polymorphisms in a Pakistani Punjabi population.
Eight single nucleotide polymorphisms showed a strong association with Type 2 diabetes in the Pakistani population.
This highlights the existence and importance of sub‐population heterogeneity.
An association with an alternate allele for KCNQ1 and KLF14 genes was identified. |
| doi_str_mv | 10.1111/dme.13012 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1808644981</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1808644981</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4942-c321f02d88d0a74da51321bb230a56f9437040a268d1224cc95ff05ad4751cf13</originalsourceid><addsrcrecordid>eNqN0U9LHDEYBvBQLHW1PfgFJOClPYzmzZ9JchRrVVDrYVtpLyEzyUB2Z2fGZKZ1v73RVQ-FgrkEwu99SPIgtAfkEPI6cit_CIwAfYdmwEteCK5hC82I5LRgRMI22klpQbLQTH9A27TkWmuAGfp1jKMf2lDbMfQdTuPk1rhvMNd4vh48ptgFW_nRJxxDWuI_NgbbjQmHDlt8M3ULWwV8Y5chjbYLeOiHqX3K-ojeN7ZN_tPzvot-fDudn5wXl9_PLk6OL4ua63y9mlFoCHVKOWIld1ZAPqkqyogVZaM5k4QTS0vlgFJe11o0DRHWcSmgboDtos-b3CH2d5NPo1mFVPu2tZ3vp2RAEVVyrtWbqJBCcdCZHvxDF_0Uu_yQR8WVoEzJrL5sVB37lKJvzBDDysa1AWIeqzG5GvNUTbb7z4lTtfLuVb50kcHRBvwNrV__P8l8vTp9iSw2E_nz_f3rhI1LU0omhbm9PjPnv-HnHNSVuWUPdq6j2w</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1804852387</pqid></control><display><type>article</type><title>A replication study of 49 Type 2 diabetes risk variants in a Punjabi Pakistani population</title><source>MEDLINE</source><source>Wiley Journals</source><creator>Zia, A. ; Wang, X. ; Bhatti, A. ; Demirci, F. Y. ; Zhao, W. ; Rasheed, A. ; Samuel, M. ; Kiani, A. K. ; Ismail, M. ; Zafar, J. ; John, P. ; Saleheen, D. ; Kamboh, M. I.</creator><creatorcontrib>Zia, A. ; Wang, X. ; Bhatti, A. ; Demirci, F. Y. ; Zhao, W. ; Rasheed, A. ; Samuel, M. ; Kiani, A. K. ; Ismail, M. ; Zafar, J. ; John, P. ; Saleheen, D. ; Kamboh, M. I.</creatorcontrib><description>Aim
The burden of Type 2 diabetes is alarmingly high in South Asia, a region that has many genetically diverse ethnic populations. Genome‐wide association studies (GWAS) conducted largely in European populations have identified a number of loci predisposing to Type 2 diabetes risk, however, the relevance of such genetic loci in many South Asian sub‐ethnicities remains elusive. The aim of this study was to replicate 49 single nucleotide polymorphisms (SNPs) previously identified through GWAS in Punjabis living in Pakistan.
Methods
We examined the association of 49 SNPs in 853 Type 2 diabetes cases and 1945 controls using additive logistic regression models after adjusting for age and gender.
Results
Of the 49 SNPs investigated, eight showed a nominal association (P < 0.05) that also remained significant after controlling for the false discovery rate. The most significant association was found for rs7903146 at the TCF7L2 locus. For a per unit increase in the risk score comprising of all the 49 SNPs, the odds ratio in association with Type 2 diabetes risk was 1.16 (95% CI 1.13–1.19, P < 2.0E–16).
Conclusion
These results suggest that some Type 2 diabetes susceptibility loci are shared between Europeans and Punjabis living in Pakistan.
What's new?
There have been limited studies on the genetic basis of Type 2 diabetes in the Pakistani population.
This study aimed to replicate 49 genome‐wide association studies significant single nucleotide polymorphisms in a Pakistani Punjabi population.
Eight single nucleotide polymorphisms showed a strong association with Type 2 diabetes in the Pakistani population.
This highlights the existence and importance of sub‐population heterogeneity.
An association with an alternate allele for KCNQ1 and KLF14 genes was identified.</description><identifier>ISSN: 0742-3071</identifier><identifier>EISSN: 1464-5491</identifier><identifier>DOI: 10.1111/dme.13012</identifier><identifier>PMID: 26499911</identifier><identifier>CODEN: DIMEEV</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Adult ; Asian Continental Ancestry Group - genetics ; Case-Control Studies ; Diabetes ; Diabetes Mellitus, Type 2 - genetics ; Female ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Genomes ; Humans ; Logistic Models ; Male ; Middle Aged ; Odds Ratio ; Pakistan ; Polymorphism ; Polymorphism, Single Nucleotide ; Population ; Reproducibility of Results ; Studies</subject><ispartof>Diabetic medicine, 2016-08, Vol.33 (8), p.1112-1117</ispartof><rights>2015 Diabetes UK</rights><rights>2015 Diabetes UK.</rights><rights>Diabetic Medicine © 2016 Diabetes UK</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4942-c321f02d88d0a74da51321bb230a56f9437040a268d1224cc95ff05ad4751cf13</citedby><cites>FETCH-LOGICAL-c4942-c321f02d88d0a74da51321bb230a56f9437040a268d1224cc95ff05ad4751cf13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fdme.13012$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fdme.13012$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26499911$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zia, A.</creatorcontrib><creatorcontrib>Wang, X.</creatorcontrib><creatorcontrib>Bhatti, A.</creatorcontrib><creatorcontrib>Demirci, F. Y.</creatorcontrib><creatorcontrib>Zhao, W.</creatorcontrib><creatorcontrib>Rasheed, A.</creatorcontrib><creatorcontrib>Samuel, M.</creatorcontrib><creatorcontrib>Kiani, A. K.</creatorcontrib><creatorcontrib>Ismail, M.</creatorcontrib><creatorcontrib>Zafar, J.</creatorcontrib><creatorcontrib>John, P.</creatorcontrib><creatorcontrib>Saleheen, D.</creatorcontrib><creatorcontrib>Kamboh, M. I.</creatorcontrib><title>A replication study of 49 Type 2 diabetes risk variants in a Punjabi Pakistani population</title><title>Diabetic medicine</title><addtitle>Diabet. Med</addtitle><description>Aim
The burden of Type 2 diabetes is alarmingly high in South Asia, a region that has many genetically diverse ethnic populations. Genome‐wide association studies (GWAS) conducted largely in European populations have identified a number of loci predisposing to Type 2 diabetes risk, however, the relevance of such genetic loci in many South Asian sub‐ethnicities remains elusive. The aim of this study was to replicate 49 single nucleotide polymorphisms (SNPs) previously identified through GWAS in Punjabis living in Pakistan.
Methods
We examined the association of 49 SNPs in 853 Type 2 diabetes cases and 1945 controls using additive logistic regression models after adjusting for age and gender.
Results
Of the 49 SNPs investigated, eight showed a nominal association (P < 0.05) that also remained significant after controlling for the false discovery rate. The most significant association was found for rs7903146 at the TCF7L2 locus. For a per unit increase in the risk score comprising of all the 49 SNPs, the odds ratio in association with Type 2 diabetes risk was 1.16 (95% CI 1.13–1.19, P < 2.0E–16).
Conclusion
These results suggest that some Type 2 diabetes susceptibility loci are shared between Europeans and Punjabis living in Pakistan.
What's new?
There have been limited studies on the genetic basis of Type 2 diabetes in the Pakistani population.
This study aimed to replicate 49 genome‐wide association studies significant single nucleotide polymorphisms in a Pakistani Punjabi population.
Eight single nucleotide polymorphisms showed a strong association with Type 2 diabetes in the Pakistani population.
This highlights the existence and importance of sub‐population heterogeneity.
An association with an alternate allele for KCNQ1 and KLF14 genes was identified.</description><subject>Adult</subject><subject>Asian Continental Ancestry Group - genetics</subject><subject>Case-Control Studies</subject><subject>Diabetes</subject><subject>Diabetes Mellitus, Type 2 - genetics</subject><subject>Female</subject><subject>Genetic Predisposition to Disease</subject><subject>Genome-Wide Association Study</subject><subject>Genomes</subject><subject>Humans</subject><subject>Logistic Models</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Odds Ratio</subject><subject>Pakistan</subject><subject>Polymorphism</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Population</subject><subject>Reproducibility of Results</subject><subject>Studies</subject><issn>0742-3071</issn><issn>1464-5491</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqN0U9LHDEYBvBQLHW1PfgFJOClPYzmzZ9JchRrVVDrYVtpLyEzyUB2Z2fGZKZ1v73RVQ-FgrkEwu99SPIgtAfkEPI6cit_CIwAfYdmwEteCK5hC82I5LRgRMI22klpQbLQTH9A27TkWmuAGfp1jKMf2lDbMfQdTuPk1rhvMNd4vh48ptgFW_nRJxxDWuI_NgbbjQmHDlt8M3ULWwV8Y5chjbYLeOiHqX3K-ojeN7ZN_tPzvot-fDudn5wXl9_PLk6OL4ua63y9mlFoCHVKOWIld1ZAPqkqyogVZaM5k4QTS0vlgFJe11o0DRHWcSmgboDtos-b3CH2d5NPo1mFVPu2tZ3vp2RAEVVyrtWbqJBCcdCZHvxDF_0Uu_yQR8WVoEzJrL5sVB37lKJvzBDDysa1AWIeqzG5GvNUTbb7z4lTtfLuVb50kcHRBvwNrV__P8l8vTp9iSw2E_nz_f3rhI1LU0omhbm9PjPnv-HnHNSVuWUPdq6j2w</recordid><startdate>201608</startdate><enddate>201608</enddate><creator>Zia, A.</creator><creator>Wang, X.</creator><creator>Bhatti, A.</creator><creator>Demirci, F. Y.</creator><creator>Zhao, W.</creator><creator>Rasheed, A.</creator><creator>Samuel, M.</creator><creator>Kiani, A. K.</creator><creator>Ismail, M.</creator><creator>Zafar, J.</creator><creator>John, P.</creator><creator>Saleheen, D.</creator><creator>Kamboh, M. I.</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>201608</creationdate><title>A replication study of 49 Type 2 diabetes risk variants in a Punjabi Pakistani population</title><author>Zia, A. ; Wang, X. ; Bhatti, A. ; Demirci, F. Y. ; Zhao, W. ; Rasheed, A. ; Samuel, M. ; Kiani, A. K. ; Ismail, M. ; Zafar, J. ; John, P. ; Saleheen, D. ; Kamboh, M. I.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4942-c321f02d88d0a74da51321bb230a56f9437040a268d1224cc95ff05ad4751cf13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>Asian Continental Ancestry Group - genetics</topic><topic>Case-Control Studies</topic><topic>Diabetes</topic><topic>Diabetes Mellitus, Type 2 - genetics</topic><topic>Female</topic><topic>Genetic Predisposition to Disease</topic><topic>Genome-Wide Association Study</topic><topic>Genomes</topic><topic>Humans</topic><topic>Logistic Models</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Odds Ratio</topic><topic>Pakistan</topic><topic>Polymorphism</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Population</topic><topic>Reproducibility of Results</topic><topic>Studies</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zia, A.</creatorcontrib><creatorcontrib>Wang, X.</creatorcontrib><creatorcontrib>Bhatti, A.</creatorcontrib><creatorcontrib>Demirci, F. Y.</creatorcontrib><creatorcontrib>Zhao, W.</creatorcontrib><creatorcontrib>Rasheed, A.</creatorcontrib><creatorcontrib>Samuel, M.</creatorcontrib><creatorcontrib>Kiani, A. K.</creatorcontrib><creatorcontrib>Ismail, M.</creatorcontrib><creatorcontrib>Zafar, J.</creatorcontrib><creatorcontrib>John, P.</creatorcontrib><creatorcontrib>Saleheen, D.</creatorcontrib><creatorcontrib>Kamboh, M. I.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Diabetic medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zia, A.</au><au>Wang, X.</au><au>Bhatti, A.</au><au>Demirci, F. Y.</au><au>Zhao, W.</au><au>Rasheed, A.</au><au>Samuel, M.</au><au>Kiani, A. K.</au><au>Ismail, M.</au><au>Zafar, J.</au><au>John, P.</au><au>Saleheen, D.</au><au>Kamboh, M. I.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A replication study of 49 Type 2 diabetes risk variants in a Punjabi Pakistani population</atitle><jtitle>Diabetic medicine</jtitle><addtitle>Diabet. Med</addtitle><date>2016-08</date><risdate>2016</risdate><volume>33</volume><issue>8</issue><spage>1112</spage><epage>1117</epage><pages>1112-1117</pages><issn>0742-3071</issn><eissn>1464-5491</eissn><coden>DIMEEV</coden><abstract>Aim
The burden of Type 2 diabetes is alarmingly high in South Asia, a region that has many genetically diverse ethnic populations. Genome‐wide association studies (GWAS) conducted largely in European populations have identified a number of loci predisposing to Type 2 diabetes risk, however, the relevance of such genetic loci in many South Asian sub‐ethnicities remains elusive. The aim of this study was to replicate 49 single nucleotide polymorphisms (SNPs) previously identified through GWAS in Punjabis living in Pakistan.
Methods
We examined the association of 49 SNPs in 853 Type 2 diabetes cases and 1945 controls using additive logistic regression models after adjusting for age and gender.
Results
Of the 49 SNPs investigated, eight showed a nominal association (P < 0.05) that also remained significant after controlling for the false discovery rate. The most significant association was found for rs7903146 at the TCF7L2 locus. For a per unit increase in the risk score comprising of all the 49 SNPs, the odds ratio in association with Type 2 diabetes risk was 1.16 (95% CI 1.13–1.19, P < 2.0E–16).
Conclusion
These results suggest that some Type 2 diabetes susceptibility loci are shared between Europeans and Punjabis living in Pakistan.
What's new?
There have been limited studies on the genetic basis of Type 2 diabetes in the Pakistani population.
This study aimed to replicate 49 genome‐wide association studies significant single nucleotide polymorphisms in a Pakistani Punjabi population.
Eight single nucleotide polymorphisms showed a strong association with Type 2 diabetes in the Pakistani population.
This highlights the existence and importance of sub‐population heterogeneity.
An association with an alternate allele for KCNQ1 and KLF14 genes was identified.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>26499911</pmid><doi>10.1111/dme.13012</doi><tpages>6</tpages></addata></record> |
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| ispartof | Diabetic medicine, 2016-08, Vol.33 (8), p.1112-1117 |
| issn | 0742-3071 1464-5491 |
| language | eng |
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| source | MEDLINE; Wiley Journals |
| subjects | Adult Asian Continental Ancestry Group - genetics Case-Control Studies Diabetes Diabetes Mellitus, Type 2 - genetics Female Genetic Predisposition to Disease Genome-Wide Association Study Genomes Humans Logistic Models Male Middle Aged Odds Ratio Pakistan Polymorphism Polymorphism, Single Nucleotide Population Reproducibility of Results Studies |
| title | A replication study of 49 Type 2 diabetes risk variants in a Punjabi Pakistani population |
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