Nonsynonymous Variants in PAX4 and GLP1R Are Associated With Type 2 Diabetes in an East Asian Population
We investigated ethnicity-specific exonic variants of type 2 diabetes (T2D) and its related clinical phenotypes in an East Asian population. We performed whole-exome sequencing in 917 T2D case and control subjects, and the findings were validated by exome array genotyping in 3,026 participants. In s...
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| Veröffentlicht in: | Diabetes (New York, N.Y.) N.Y.), 2018-09, Vol.67 (9), p.1892-1902 |
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| creator | Kwak, Soo Heon Chae, Jeesoo Lee, Seungbok Choi, Sungkyoung Koo, Bo Kyung Yoon, Ji Won Park, Jin-Ho Cho, Belong Moon, Min Kyong Lim, Soo Cho, Young Min Moon, Sanghoon Kim, Young Jin Han, Sohee Hwang, Mi Yeong Cho, Yoon Shin Lee, Myung-Shik Jang, Hak C Kang, Hyun Min Park, Taesung Cho, Nam H Kim, Kyunga Kim, Jong-Il Park, Kyong Soo |
| description | We investigated ethnicity-specific exonic variants of type 2 diabetes (T2D) and its related clinical phenotypes in an East Asian population. We performed whole-exome sequencing in 917 T2D case and control subjects, and the findings were validated by exome array genotyping in 3,026 participants. In silico replication was conducted for seven nonsynonymous variants in an additional 13,122 participants. Single-variant and gene-based association tests for T2D were analyzed. A total of 728,838 variants were identified by whole-exome sequencing. Among nonsynonymous variants,
Arg192His increased risk of T2D and
Arg131Gln decreased risk of T2D in genome-wide significance (odds ratio [OR] 1.48,
= 4.47 × 10
and OR 0.84,
= 3.55 × 10
, respectively). Another variant at
192 codon Arg192Ser was nominally associated with T2D (OR 1.62,
= 5.18 × 10
). In T2D patients,
Arg192His was associated with earlier age at diagnosis, and
Arg131Gln was associated with decreased risk of cardiovascular disease. In control subjects without diabetes, the
Arg192His was associated with higher fasting glucose and
Arg131Gln was associated with lower fasting glucose and HbA
level. Gene-based analysis revealed that
was most significantly associated with decreased risk of T2D (
= 1.0 × 10
). In summary, we have identified nonsynonymous variants associated with risk of T2D and related phenotypes in Koreans. |
| doi_str_mv | 10.2337/db18-0361 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2059563151</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2108744782</sourcerecordid><originalsourceid>FETCH-LOGICAL-c388t-6cd4ca7678b33162981a83c894ad8d0de86c151e3c4ff0953850be48f6cb41fb3</originalsourceid><addsrcrecordid>eNpdkLtOwzAUQC0EoqUw8APIEgsMAb-S2GNUSkGqoEIFukWO46ipEjvEyZC_x6WFAXm4y7lH1weAS4zuCKXxfZ5hHiAa4SMwxoKKgJJ4fQzGCGES4FjEI3Dm3BYhFPl3CkZECIYZi8dg82KNG4w1Q217Bz9kW0rTOVgauEzWDEqTw_liid9g0mqYOGdVKTudw8-y28DV0GhI4EMpM93pny1p4Ey6zqNeBJe26SvZldacg5NCVk5fHOYEvD_OVtOnYPE6f54mi0BRzrsgUjlTMo5inlGKIyI4lpwqLpjMeY5yzSOFQ6ypYkWBREh5iDLNeBGpjOEioxNws_c2rf3qtevSunRKV5U02v8wJSgUYUS9w6PX_9Ct7Vvjr0sJRjz2gTjx1O2eUq11rtVF2rRlLdshxSjd5U93-dNdfs9eHYx9Vuv8j_ztTb8Bb6p9Xw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2108744782</pqid></control><display><type>article</type><title>Nonsynonymous Variants in PAX4 and GLP1R Are Associated With Type 2 Diabetes in an East Asian Population</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Kwak, Soo Heon ; Chae, Jeesoo ; Lee, Seungbok ; Choi, Sungkyoung ; Koo, Bo Kyung ; Yoon, Ji Won ; Park, Jin-Ho ; Cho, Belong ; Moon, Min Kyong ; Lim, Soo ; Cho, Young Min ; Moon, Sanghoon ; Kim, Young Jin ; Han, Sohee ; Hwang, Mi Yeong ; Cho, Yoon Shin ; Lee, Myung-Shik ; Jang, Hak C ; Kang, Hyun Min ; Park, Taesung ; Cho, Nam H ; Kim, Kyunga ; Kim, Jong-Il ; Park, Kyong Soo</creator><creatorcontrib>Kwak, Soo Heon ; Chae, Jeesoo ; Lee, Seungbok ; Choi, Sungkyoung ; Koo, Bo Kyung ; Yoon, Ji Won ; Park, Jin-Ho ; Cho, Belong ; Moon, Min Kyong ; Lim, Soo ; Cho, Young Min ; Moon, Sanghoon ; Kim, Young Jin ; Han, Sohee ; Hwang, Mi Yeong ; Cho, Yoon Shin ; Lee, Myung-Shik ; Jang, Hak C ; Kang, Hyun Min ; Park, Taesung ; Cho, Nam H ; Kim, Kyunga ; Kim, Jong-Il ; Park, Kyong Soo</creatorcontrib><description>We investigated ethnicity-specific exonic variants of type 2 diabetes (T2D) and its related clinical phenotypes in an East Asian population. We performed whole-exome sequencing in 917 T2D case and control subjects, and the findings were validated by exome array genotyping in 3,026 participants. In silico replication was conducted for seven nonsynonymous variants in an additional 13,122 participants. Single-variant and gene-based association tests for T2D were analyzed. A total of 728,838 variants were identified by whole-exome sequencing. Among nonsynonymous variants,
Arg192His increased risk of T2D and
Arg131Gln decreased risk of T2D in genome-wide significance (odds ratio [OR] 1.48,
= 4.47 × 10
and OR 0.84,
= 3.55 × 10
, respectively). Another variant at
192 codon Arg192Ser was nominally associated with T2D (OR 1.62,
= 5.18 × 10
). In T2D patients,
Arg192His was associated with earlier age at diagnosis, and
Arg131Gln was associated with decreased risk of cardiovascular disease. In control subjects without diabetes, the
Arg192His was associated with higher fasting glucose and
Arg131Gln was associated with lower fasting glucose and HbA
level. Gene-based analysis revealed that
was most significantly associated with decreased risk of T2D (
= 1.0 × 10
). In summary, we have identified nonsynonymous variants associated with risk of T2D and related phenotypes in Koreans.</description><identifier>ISSN: 0012-1797</identifier><identifier>EISSN: 1939-327X</identifier><identifier>DOI: 10.2337/db18-0361</identifier><identifier>PMID: 29941447</identifier><language>eng</language><publisher>United States: American Diabetes Association</publisher><subject>Aged ; Alleles ; Amino Acid Substitution ; Asian Continental Ancestry Group ; Cardiovascular diseases ; Cardiovascular system ; Case-Control Studies ; Cohort Studies ; Computational Biology ; Databases, Genetic ; Diabetes ; Diabetes mellitus ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Type 2 - genetics ; Diabetes Mellitus, Type 2 - metabolism ; Disease prevention ; Expert Systems ; Fasting ; Female ; Gene Frequency ; Genetic Association Studies ; Genetic Predisposition to Disease ; Genetic Variation ; Genome-Wide Association Study ; Genomes ; Genotype & phenotype ; Genotyping ; Glucagon-Like Peptide-1 Receptor - chemistry ; Glucagon-Like Peptide-1 Receptor - genetics ; Glucagon-Like Peptide-1 Receptor - metabolism ; Homeodomain Proteins - chemistry ; Homeodomain Proteins - genetics ; Homeodomain Proteins - metabolism ; Humans ; Laboratory testing ; Male ; Middle Aged ; Minority & ethnic groups ; Paired Box Transcription Factors - chemistry ; Paired Box Transcription Factors - genetics ; Paired Box Transcription Factors - metabolism ; Phenotypes ; Polymorphism, Single Nucleotide ; Population genetics ; Republic of Korea ; Whole Exome Sequencing</subject><ispartof>Diabetes (New York, N.Y.), 2018-09, Vol.67 (9), p.1892-1902</ispartof><rights>2018 by the American Diabetes Association.</rights><rights>Copyright American Diabetes Association Sep 1, 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c388t-6cd4ca7678b33162981a83c894ad8d0de86c151e3c4ff0953850be48f6cb41fb3</citedby><cites>FETCH-LOGICAL-c388t-6cd4ca7678b33162981a83c894ad8d0de86c151e3c4ff0953850be48f6cb41fb3</cites><orcidid>0000-0002-5460-2846 ; 0000-0002-4137-1671 ; 0000-0002-2331-6126 ; 0000-0003-3597-342X ; 0000-0002-4188-6536</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27922,27923</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29941447$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kwak, Soo Heon</creatorcontrib><creatorcontrib>Chae, Jeesoo</creatorcontrib><creatorcontrib>Lee, Seungbok</creatorcontrib><creatorcontrib>Choi, Sungkyoung</creatorcontrib><creatorcontrib>Koo, Bo Kyung</creatorcontrib><creatorcontrib>Yoon, Ji Won</creatorcontrib><creatorcontrib>Park, Jin-Ho</creatorcontrib><creatorcontrib>Cho, Belong</creatorcontrib><creatorcontrib>Moon, Min Kyong</creatorcontrib><creatorcontrib>Lim, Soo</creatorcontrib><creatorcontrib>Cho, Young Min</creatorcontrib><creatorcontrib>Moon, Sanghoon</creatorcontrib><creatorcontrib>Kim, Young Jin</creatorcontrib><creatorcontrib>Han, Sohee</creatorcontrib><creatorcontrib>Hwang, Mi Yeong</creatorcontrib><creatorcontrib>Cho, Yoon Shin</creatorcontrib><creatorcontrib>Lee, Myung-Shik</creatorcontrib><creatorcontrib>Jang, Hak C</creatorcontrib><creatorcontrib>Kang, Hyun Min</creatorcontrib><creatorcontrib>Park, Taesung</creatorcontrib><creatorcontrib>Cho, Nam H</creatorcontrib><creatorcontrib>Kim, Kyunga</creatorcontrib><creatorcontrib>Kim, Jong-Il</creatorcontrib><creatorcontrib>Park, Kyong Soo</creatorcontrib><title>Nonsynonymous Variants in PAX4 and GLP1R Are Associated With Type 2 Diabetes in an East Asian Population</title><title>Diabetes (New York, N.Y.)</title><addtitle>Diabetes</addtitle><description>We investigated ethnicity-specific exonic variants of type 2 diabetes (T2D) and its related clinical phenotypes in an East Asian population. We performed whole-exome sequencing in 917 T2D case and control subjects, and the findings were validated by exome array genotyping in 3,026 participants. In silico replication was conducted for seven nonsynonymous variants in an additional 13,122 participants. Single-variant and gene-based association tests for T2D were analyzed. A total of 728,838 variants were identified by whole-exome sequencing. Among nonsynonymous variants,
Arg192His increased risk of T2D and
Arg131Gln decreased risk of T2D in genome-wide significance (odds ratio [OR] 1.48,
= 4.47 × 10
and OR 0.84,
= 3.55 × 10
, respectively). Another variant at
192 codon Arg192Ser was nominally associated with T2D (OR 1.62,
= 5.18 × 10
). In T2D patients,
Arg192His was associated with earlier age at diagnosis, and
Arg131Gln was associated with decreased risk of cardiovascular disease. In control subjects without diabetes, the
Arg192His was associated with higher fasting glucose and
Arg131Gln was associated with lower fasting glucose and HbA
level. Gene-based analysis revealed that
was most significantly associated with decreased risk of T2D (
= 1.0 × 10
). In summary, we have identified nonsynonymous variants associated with risk of T2D and related phenotypes in Koreans.</description><subject>Aged</subject><subject>Alleles</subject><subject>Amino Acid Substitution</subject><subject>Asian Continental Ancestry Group</subject><subject>Cardiovascular diseases</subject><subject>Cardiovascular system</subject><subject>Case-Control Studies</subject><subject>Cohort Studies</subject><subject>Computational Biology</subject><subject>Databases, Genetic</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Diabetes Mellitus, Type 2 - genetics</subject><subject>Diabetes Mellitus, Type 2 - metabolism</subject><subject>Disease prevention</subject><subject>Expert Systems</subject><subject>Fasting</subject><subject>Female</subject><subject>Gene Frequency</subject><subject>Genetic Association Studies</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetic Variation</subject><subject>Genome-Wide Association Study</subject><subject>Genomes</subject><subject>Genotype & phenotype</subject><subject>Genotyping</subject><subject>Glucagon-Like Peptide-1 Receptor - chemistry</subject><subject>Glucagon-Like Peptide-1 Receptor - genetics</subject><subject>Glucagon-Like Peptide-1 Receptor - metabolism</subject><subject>Homeodomain Proteins - chemistry</subject><subject>Homeodomain Proteins - genetics</subject><subject>Homeodomain Proteins - metabolism</subject><subject>Humans</subject><subject>Laboratory testing</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Minority & ethnic groups</subject><subject>Paired Box Transcription Factors - chemistry</subject><subject>Paired Box Transcription Factors - genetics</subject><subject>Paired Box Transcription Factors - metabolism</subject><subject>Phenotypes</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Population genetics</subject><subject>Republic of Korea</subject><subject>Whole Exome Sequencing</subject><issn>0012-1797</issn><issn>1939-327X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkLtOwzAUQC0EoqUw8APIEgsMAb-S2GNUSkGqoEIFukWO46ipEjvEyZC_x6WFAXm4y7lH1weAS4zuCKXxfZ5hHiAa4SMwxoKKgJJ4fQzGCGES4FjEI3Dm3BYhFPl3CkZECIYZi8dg82KNG4w1Q217Bz9kW0rTOVgauEzWDEqTw_liid9g0mqYOGdVKTudw8-y28DV0GhI4EMpM93pny1p4Ey6zqNeBJe26SvZldacg5NCVk5fHOYEvD_OVtOnYPE6f54mi0BRzrsgUjlTMo5inlGKIyI4lpwqLpjMeY5yzSOFQ6ypYkWBREh5iDLNeBGpjOEioxNws_c2rf3qtevSunRKV5U02v8wJSgUYUS9w6PX_9Ct7Vvjr0sJRjz2gTjx1O2eUq11rtVF2rRlLdshxSjd5U93-dNdfs9eHYx9Vuv8j_ztTb8Bb6p9Xw</recordid><startdate>201809</startdate><enddate>201809</enddate><creator>Kwak, Soo Heon</creator><creator>Chae, Jeesoo</creator><creator>Lee, Seungbok</creator><creator>Choi, Sungkyoung</creator><creator>Koo, Bo Kyung</creator><creator>Yoon, Ji Won</creator><creator>Park, Jin-Ho</creator><creator>Cho, Belong</creator><creator>Moon, Min Kyong</creator><creator>Lim, Soo</creator><creator>Cho, Young Min</creator><creator>Moon, Sanghoon</creator><creator>Kim, Young Jin</creator><creator>Han, Sohee</creator><creator>Hwang, Mi Yeong</creator><creator>Cho, Yoon Shin</creator><creator>Lee, Myung-Shik</creator><creator>Jang, Hak C</creator><creator>Kang, Hyun Min</creator><creator>Park, Taesung</creator><creator>Cho, Nam H</creator><creator>Kim, Kyunga</creator><creator>Kim, Jong-Il</creator><creator>Park, Kyong Soo</creator><general>American Diabetes Association</general><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>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-5460-2846</orcidid><orcidid>https://orcid.org/0000-0002-4137-1671</orcidid><orcidid>https://orcid.org/0000-0002-2331-6126</orcidid><orcidid>https://orcid.org/0000-0003-3597-342X</orcidid><orcidid>https://orcid.org/0000-0002-4188-6536</orcidid></search><sort><creationdate>201809</creationdate><title>Nonsynonymous Variants in PAX4 and GLP1R Are Associated With Type 2 Diabetes in an East Asian Population</title><author>Kwak, Soo Heon ; Chae, Jeesoo ; Lee, Seungbok ; Choi, Sungkyoung ; Koo, Bo Kyung ; Yoon, Ji Won ; Park, Jin-Ho ; Cho, Belong ; Moon, Min Kyong ; Lim, Soo ; Cho, Young Min ; Moon, Sanghoon ; Kim, Young Jin ; Han, Sohee ; Hwang, Mi Yeong ; Cho, Yoon Shin ; Lee, Myung-Shik ; Jang, Hak C ; Kang, Hyun Min ; Park, Taesung ; Cho, Nam H ; Kim, Kyunga ; Kim, Jong-Il ; Park, Kyong Soo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c388t-6cd4ca7678b33162981a83c894ad8d0de86c151e3c4ff0953850be48f6cb41fb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Aged</topic><topic>Alleles</topic><topic>Amino Acid Substitution</topic><topic>Asian Continental Ancestry Group</topic><topic>Cardiovascular diseases</topic><topic>Cardiovascular system</topic><topic>Case-Control Studies</topic><topic>Cohort Studies</topic><topic>Computational Biology</topic><topic>Databases, Genetic</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>Diabetes Mellitus, Type 2 - genetics</topic><topic>Diabetes Mellitus, Type 2 - metabolism</topic><topic>Disease prevention</topic><topic>Expert Systems</topic><topic>Fasting</topic><topic>Female</topic><topic>Gene Frequency</topic><topic>Genetic Association Studies</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetic Variation</topic><topic>Genome-Wide Association Study</topic><topic>Genomes</topic><topic>Genotype & phenotype</topic><topic>Genotyping</topic><topic>Glucagon-Like Peptide-1 Receptor - chemistry</topic><topic>Glucagon-Like Peptide-1 Receptor - genetics</topic><topic>Glucagon-Like Peptide-1 Receptor - metabolism</topic><topic>Homeodomain Proteins - chemistry</topic><topic>Homeodomain Proteins - genetics</topic><topic>Homeodomain Proteins - metabolism</topic><topic>Humans</topic><topic>Laboratory testing</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Minority & ethnic groups</topic><topic>Paired Box Transcription Factors - chemistry</topic><topic>Paired Box Transcription Factors - genetics</topic><topic>Paired Box Transcription Factors - metabolism</topic><topic>Phenotypes</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Population genetics</topic><topic>Republic of Korea</topic><topic>Whole Exome Sequencing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kwak, Soo Heon</creatorcontrib><creatorcontrib>Chae, Jeesoo</creatorcontrib><creatorcontrib>Lee, Seungbok</creatorcontrib><creatorcontrib>Choi, Sungkyoung</creatorcontrib><creatorcontrib>Koo, Bo Kyung</creatorcontrib><creatorcontrib>Yoon, Ji Won</creatorcontrib><creatorcontrib>Park, Jin-Ho</creatorcontrib><creatorcontrib>Cho, Belong</creatorcontrib><creatorcontrib>Moon, Min Kyong</creatorcontrib><creatorcontrib>Lim, Soo</creatorcontrib><creatorcontrib>Cho, Young Min</creatorcontrib><creatorcontrib>Moon, Sanghoon</creatorcontrib><creatorcontrib>Kim, Young Jin</creatorcontrib><creatorcontrib>Han, Sohee</creatorcontrib><creatorcontrib>Hwang, Mi Yeong</creatorcontrib><creatorcontrib>Cho, Yoon Shin</creatorcontrib><creatorcontrib>Lee, Myung-Shik</creatorcontrib><creatorcontrib>Jang, Hak C</creatorcontrib><creatorcontrib>Kang, Hyun Min</creatorcontrib><creatorcontrib>Park, Taesung</creatorcontrib><creatorcontrib>Cho, Nam H</creatorcontrib><creatorcontrib>Kim, Kyunga</creatorcontrib><creatorcontrib>Kim, Jong-Il</creatorcontrib><creatorcontrib>Park, Kyong Soo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Diabetes (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kwak, Soo Heon</au><au>Chae, Jeesoo</au><au>Lee, Seungbok</au><au>Choi, Sungkyoung</au><au>Koo, Bo Kyung</au><au>Yoon, Ji Won</au><au>Park, Jin-Ho</au><au>Cho, Belong</au><au>Moon, Min Kyong</au><au>Lim, Soo</au><au>Cho, Young Min</au><au>Moon, Sanghoon</au><au>Kim, Young Jin</au><au>Han, Sohee</au><au>Hwang, Mi Yeong</au><au>Cho, Yoon Shin</au><au>Lee, Myung-Shik</au><au>Jang, Hak C</au><au>Kang, Hyun Min</au><au>Park, Taesung</au><au>Cho, Nam H</au><au>Kim, Kyunga</au><au>Kim, Jong-Il</au><au>Park, Kyong Soo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nonsynonymous Variants in PAX4 and GLP1R Are Associated With Type 2 Diabetes in an East Asian Population</atitle><jtitle>Diabetes (New York, N.Y.)</jtitle><addtitle>Diabetes</addtitle><date>2018-09</date><risdate>2018</risdate><volume>67</volume><issue>9</issue><spage>1892</spage><epage>1902</epage><pages>1892-1902</pages><issn>0012-1797</issn><eissn>1939-327X</eissn><abstract>We investigated ethnicity-specific exonic variants of type 2 diabetes (T2D) and its related clinical phenotypes in an East Asian population. We performed whole-exome sequencing in 917 T2D case and control subjects, and the findings were validated by exome array genotyping in 3,026 participants. In silico replication was conducted for seven nonsynonymous variants in an additional 13,122 participants. Single-variant and gene-based association tests for T2D were analyzed. A total of 728,838 variants were identified by whole-exome sequencing. Among nonsynonymous variants,
Arg192His increased risk of T2D and
Arg131Gln decreased risk of T2D in genome-wide significance (odds ratio [OR] 1.48,
= 4.47 × 10
and OR 0.84,
= 3.55 × 10
, respectively). Another variant at
192 codon Arg192Ser was nominally associated with T2D (OR 1.62,
= 5.18 × 10
). In T2D patients,
Arg192His was associated with earlier age at diagnosis, and
Arg131Gln was associated with decreased risk of cardiovascular disease. In control subjects without diabetes, the
Arg192His was associated with higher fasting glucose and
Arg131Gln was associated with lower fasting glucose and HbA
level. Gene-based analysis revealed that
was most significantly associated with decreased risk of T2D (
= 1.0 × 10
). In summary, we have identified nonsynonymous variants associated with risk of T2D and related phenotypes in Koreans.</abstract><cop>United States</cop><pub>American Diabetes Association</pub><pmid>29941447</pmid><doi>10.2337/db18-0361</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-5460-2846</orcidid><orcidid>https://orcid.org/0000-0002-4137-1671</orcidid><orcidid>https://orcid.org/0000-0002-2331-6126</orcidid><orcidid>https://orcid.org/0000-0003-3597-342X</orcidid><orcidid>https://orcid.org/0000-0002-4188-6536</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0012-1797 |
| ispartof | Diabetes (New York, N.Y.), 2018-09, Vol.67 (9), p.1892-1902 |
| issn | 0012-1797 1939-327X |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2059563151 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Aged Alleles Amino Acid Substitution Asian Continental Ancestry Group Cardiovascular diseases Cardiovascular system Case-Control Studies Cohort Studies Computational Biology Databases, Genetic Diabetes Diabetes mellitus Diabetes mellitus (non-insulin dependent) Diabetes Mellitus, Type 2 - genetics Diabetes Mellitus, Type 2 - metabolism Disease prevention Expert Systems Fasting Female Gene Frequency Genetic Association Studies Genetic Predisposition to Disease Genetic Variation Genome-Wide Association Study Genomes Genotype & phenotype Genotyping Glucagon-Like Peptide-1 Receptor - chemistry Glucagon-Like Peptide-1 Receptor - genetics Glucagon-Like Peptide-1 Receptor - metabolism Homeodomain Proteins - chemistry Homeodomain Proteins - genetics Homeodomain Proteins - metabolism Humans Laboratory testing Male Middle Aged Minority & ethnic groups Paired Box Transcription Factors - chemistry Paired Box Transcription Factors - genetics Paired Box Transcription Factors - metabolism Phenotypes Polymorphism, Single Nucleotide Population genetics Republic of Korea Whole Exome Sequencing |
| title | Nonsynonymous Variants in PAX4 and GLP1R Are Associated With Type 2 Diabetes in an East Asian Population |
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