Whole‐genome sequencing study in Koreans identifies novel loci for Alzheimer's disease
INTRODUCTION The genetic basis of Alzheimer's disease (AD) in Koreans is poorly understood. METHODS We performed an AD genome‐wide association study using whole‐genome sequence data from 3540 Koreans (1583 AD cases, 1957 controls) and single‐nucleotide polymorphism array data from 2978 Japanese...
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| Veröffentlicht in: | Alzheimer's & dementia 2024-12, Vol.20 (12), p.8246-8262 |
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| creator | Kang, Moonil Farrell, John J. Zhu, Congcong Park, Hyeonseul Kang, Sarang Seo, Eun Hyun Choi, Kyu Yeong Jun, Gyungah R. Won, Sungho Gim, Jungsoo Lee, Kun Ho Farrer, Lindsay A. |
| description | INTRODUCTION
The genetic basis of Alzheimer's disease (AD) in Koreans is poorly understood.
METHODS
We performed an AD genome‐wide association study using whole‐genome sequence data from 3540 Koreans (1583 AD cases, 1957 controls) and single‐nucleotide polymorphism array data from 2978 Japanese (1336 AD cases, 1642 controls). Significant findings were evaluated by pathway enrichment and differential gene expression analysis in brain tissue from controls and AD cases with and without dementia prior to death.
RESULTS
We identified genome‐wide significant associations with APOE in the total sample and ROCK2 (rs76484417, p = 2.71×10−8) among APOE ε4 non‐carriers. A study‐wide significant association was found with aggregated rare variants in MICALL1 (MICAL like 1) (p = 9.04×10−7). Several novel AD‐associated genes, including ROCK2 and MICALL1, were differentially expressed in AD cases compared to controls (p |
| doi_str_mv | 10.1002/alz.14128 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11667495</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3118833972</sourcerecordid><originalsourceid>FETCH-LOGICAL-c2718-c485d85bdd9cb78fcdf22eb23eecbbf3e8f223dc4cc4e6414f662c8bf116878a3</originalsourceid><addsrcrecordid>eNp1kcFOGzEQhq2KqgnQQ18A-QYcQtZe7673hCIELWokLlRUvVhee5wYee1gJ6Bw6iP0GfskdQlEcOBkW_Pp88z8CH0hxQkpCjqW7vGEMEL5BzQkVUVHFW3ane29LgZoN6XbomAFJ9UnNChbRnndsiH6eTMPDv7-_jMDH3rACe5W4JX1M5yWK73G1uPvIYL0CVsNfmmNhYR9uAeHXVAWmxDxxD3OwfYQDxPWNoFMsI8-GukSfH4-99CPi_Prs2-j6dXXy7PJdKRoQ_hIMV5pXnVat6pruFHaUAodLQFU15kSeH6XWjGlGNSMMFPXVPHOEFLzhstyD51uvItV14NWucUonVhE28u4FkFa8bbi7VzMwr3IgrphbZUNR8-GGPLwaSl6mxQ4Jz2EVRIlIZyXZdvQjB5vUBVDShHM9h9SiP9RiByFeIoiswevG9uSL7vPwHgDPFgH6_dNYjL9tVH-A_zUlw0</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3118833972</pqid></control><display><type>article</type><title>Whole‐genome sequencing study in Koreans identifies novel loci for Alzheimer's disease</title><source>MEDLINE</source><source>PubMed Central Open Access</source><source>Wiley-Blackwell Open Access Titles</source><source>Wiley Online Library All Journals</source><source>PubMed Central</source><creator>Kang, Moonil ; Farrell, John J. ; Zhu, Congcong ; Park, Hyeonseul ; Kang, Sarang ; Seo, Eun Hyun ; Choi, Kyu Yeong ; Jun, Gyungah R. ; Won, Sungho ; Gim, Jungsoo ; Lee, Kun Ho ; Farrer, Lindsay A.</creator><creatorcontrib>Kang, Moonil ; Farrell, John J. ; Zhu, Congcong ; Park, Hyeonseul ; Kang, Sarang ; Seo, Eun Hyun ; Choi, Kyu Yeong ; Jun, Gyungah R. ; Won, Sungho ; Gim, Jungsoo ; Lee, Kun Ho ; Farrer, Lindsay A.</creatorcontrib><description>INTRODUCTION
The genetic basis of Alzheimer's disease (AD) in Koreans is poorly understood.
METHODS
We performed an AD genome‐wide association study using whole‐genome sequence data from 3540 Koreans (1583 AD cases, 1957 controls) and single‐nucleotide polymorphism array data from 2978 Japanese (1336 AD cases, 1642 controls). Significant findings were evaluated by pathway enrichment and differential gene expression analysis in brain tissue from controls and AD cases with and without dementia prior to death.
RESULTS
We identified genome‐wide significant associations with APOE in the total sample and ROCK2 (rs76484417, p = 2.71×10−8) among APOE ε4 non‐carriers. A study‐wide significant association was found with aggregated rare variants in MICALL1 (MICAL like 1) (p = 9.04×10−7). Several novel AD‐associated genes, including ROCK2 and MICALL1, were differentially expressed in AD cases compared to controls (p < 3.33×10−3). ROCK2 was also differentially expressed between AD cases with and without dementia (p = 1.34×10−4).
DISCUSSION
Our results provide insight into genetic mechanisms leading to AD and cognitive resilience in East Asians.
Highlights
Novel genome‐wide significant associations for AD identified with ROCK2 and MICALL1.
ROCK2 and MICALL1 are differentially expressed between AD cases and controls in the brain.
This is the largest whole‐genome‐sequence study of AD in an East Asian population.</description><identifier>ISSN: 1552-5260</identifier><identifier>ISSN: 1552-5279</identifier><identifier>EISSN: 1552-5279</identifier><identifier>DOI: 10.1002/alz.14128</identifier><identifier>PMID: 39428694</identifier><language>eng</language><publisher>United States: John Wiley and Sons Inc</publisher><subject>Aged ; Aged, 80 and over ; Alzheimer Disease - genetics ; Alzheimer's disease ; Apolipoproteins E - genetics ; differential gene expression ; East Asian People - genetics ; Female ; Genetic Predisposition to Disease ; gene‐based association ; Genome-Wide Association Study ; Humans ; Male ; pathway enrichment ; Polymorphism, Single Nucleotide ; Republic of Korea ; rho-Associated Kinases - genetics ; Whole Genome Sequencing</subject><ispartof>Alzheimer's & dementia, 2024-12, Vol.20 (12), p.8246-8262</ispartof><rights>2024 The Author(s). published by Wiley Periodicals LLC on behalf of Alzheimer's Association.</rights><rights>2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c2718-c485d85bdd9cb78fcdf22eb23eecbbf3e8f223dc4cc4e6414f662c8bf116878a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667495/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667495/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,1417,11561,27923,27924,45573,45574,46051,46475,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39428694$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kang, Moonil</creatorcontrib><creatorcontrib>Farrell, John J.</creatorcontrib><creatorcontrib>Zhu, Congcong</creatorcontrib><creatorcontrib>Park, Hyeonseul</creatorcontrib><creatorcontrib>Kang, Sarang</creatorcontrib><creatorcontrib>Seo, Eun Hyun</creatorcontrib><creatorcontrib>Choi, Kyu Yeong</creatorcontrib><creatorcontrib>Jun, Gyungah R.</creatorcontrib><creatorcontrib>Won, Sungho</creatorcontrib><creatorcontrib>Gim, Jungsoo</creatorcontrib><creatorcontrib>Lee, Kun Ho</creatorcontrib><creatorcontrib>Farrer, Lindsay A.</creatorcontrib><title>Whole‐genome sequencing study in Koreans identifies novel loci for Alzheimer's disease</title><title>Alzheimer's & dementia</title><addtitle>Alzheimers Dement</addtitle><description>INTRODUCTION
The genetic basis of Alzheimer's disease (AD) in Koreans is poorly understood.
METHODS
We performed an AD genome‐wide association study using whole‐genome sequence data from 3540 Koreans (1583 AD cases, 1957 controls) and single‐nucleotide polymorphism array data from 2978 Japanese (1336 AD cases, 1642 controls). Significant findings were evaluated by pathway enrichment and differential gene expression analysis in brain tissue from controls and AD cases with and without dementia prior to death.
RESULTS
We identified genome‐wide significant associations with APOE in the total sample and ROCK2 (rs76484417, p = 2.71×10−8) among APOE ε4 non‐carriers. A study‐wide significant association was found with aggregated rare variants in MICALL1 (MICAL like 1) (p = 9.04×10−7). Several novel AD‐associated genes, including ROCK2 and MICALL1, were differentially expressed in AD cases compared to controls (p < 3.33×10−3). ROCK2 was also differentially expressed between AD cases with and without dementia (p = 1.34×10−4).
DISCUSSION
Our results provide insight into genetic mechanisms leading to AD and cognitive resilience in East Asians.
Highlights
Novel genome‐wide significant associations for AD identified with ROCK2 and MICALL1.
ROCK2 and MICALL1 are differentially expressed between AD cases and controls in the brain.
This is the largest whole‐genome‐sequence study of AD in an East Asian population.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Alzheimer Disease - genetics</subject><subject>Alzheimer's disease</subject><subject>Apolipoproteins E - genetics</subject><subject>differential gene expression</subject><subject>East Asian People - genetics</subject><subject>Female</subject><subject>Genetic Predisposition to Disease</subject><subject>gene‐based association</subject><subject>Genome-Wide Association Study</subject><subject>Humans</subject><subject>Male</subject><subject>pathway enrichment</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Republic of Korea</subject><subject>rho-Associated Kinases - genetics</subject><subject>Whole Genome Sequencing</subject><issn>1552-5260</issn><issn>1552-5279</issn><issn>1552-5279</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><recordid>eNp1kcFOGzEQhq2KqgnQQ18A-QYcQtZe7673hCIELWokLlRUvVhee5wYee1gJ6Bw6iP0GfskdQlEcOBkW_Pp88z8CH0hxQkpCjqW7vGEMEL5BzQkVUVHFW3ane29LgZoN6XbomAFJ9UnNChbRnndsiH6eTMPDv7-_jMDH3rACe5W4JX1M5yWK73G1uPvIYL0CVsNfmmNhYR9uAeHXVAWmxDxxD3OwfYQDxPWNoFMsI8-GukSfH4-99CPi_Prs2-j6dXXy7PJdKRoQ_hIMV5pXnVat6pruFHaUAodLQFU15kSeH6XWjGlGNSMMFPXVPHOEFLzhstyD51uvItV14NWucUonVhE28u4FkFa8bbi7VzMwr3IgrphbZUNR8-GGPLwaSl6mxQ4Jz2EVRIlIZyXZdvQjB5vUBVDShHM9h9SiP9RiByFeIoiswevG9uSL7vPwHgDPFgH6_dNYjL9tVH-A_zUlw0</recordid><startdate>202412</startdate><enddate>202412</enddate><creator>Kang, Moonil</creator><creator>Farrell, John J.</creator><creator>Zhu, Congcong</creator><creator>Park, Hyeonseul</creator><creator>Kang, Sarang</creator><creator>Seo, Eun Hyun</creator><creator>Choi, Kyu Yeong</creator><creator>Jun, Gyungah R.</creator><creator>Won, Sungho</creator><creator>Gim, Jungsoo</creator><creator>Lee, Kun Ho</creator><creator>Farrer, Lindsay A.</creator><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>202412</creationdate><title>Whole‐genome sequencing study in Koreans identifies novel loci for Alzheimer's disease</title><author>Kang, Moonil ; Farrell, John J. ; Zhu, Congcong ; Park, Hyeonseul ; Kang, Sarang ; Seo, Eun Hyun ; Choi, Kyu Yeong ; Jun, Gyungah R. ; Won, Sungho ; Gim, Jungsoo ; Lee, Kun Ho ; Farrer, Lindsay A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2718-c485d85bdd9cb78fcdf22eb23eecbbf3e8f223dc4cc4e6414f662c8bf116878a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Alzheimer Disease - genetics</topic><topic>Alzheimer's disease</topic><topic>Apolipoproteins E - genetics</topic><topic>differential gene expression</topic><topic>East Asian People - genetics</topic><topic>Female</topic><topic>Genetic Predisposition to Disease</topic><topic>gene‐based association</topic><topic>Genome-Wide Association Study</topic><topic>Humans</topic><topic>Male</topic><topic>pathway enrichment</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Republic of Korea</topic><topic>rho-Associated Kinases - genetics</topic><topic>Whole Genome Sequencing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kang, Moonil</creatorcontrib><creatorcontrib>Farrell, John J.</creatorcontrib><creatorcontrib>Zhu, Congcong</creatorcontrib><creatorcontrib>Park, Hyeonseul</creatorcontrib><creatorcontrib>Kang, Sarang</creatorcontrib><creatorcontrib>Seo, Eun Hyun</creatorcontrib><creatorcontrib>Choi, Kyu Yeong</creatorcontrib><creatorcontrib>Jun, Gyungah R.</creatorcontrib><creatorcontrib>Won, Sungho</creatorcontrib><creatorcontrib>Gim, Jungsoo</creatorcontrib><creatorcontrib>Lee, Kun Ho</creatorcontrib><creatorcontrib>Farrer, Lindsay A.</creatorcontrib><collection>Wiley-Blackwell Open Access Titles</collection><collection>Wiley Free Content</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Alzheimer's & dementia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kang, Moonil</au><au>Farrell, John J.</au><au>Zhu, Congcong</au><au>Park, Hyeonseul</au><au>Kang, Sarang</au><au>Seo, Eun Hyun</au><au>Choi, Kyu Yeong</au><au>Jun, Gyungah R.</au><au>Won, Sungho</au><au>Gim, Jungsoo</au><au>Lee, Kun Ho</au><au>Farrer, Lindsay A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Whole‐genome sequencing study in Koreans identifies novel loci for Alzheimer's disease</atitle><jtitle>Alzheimer's & dementia</jtitle><addtitle>Alzheimers Dement</addtitle><date>2024-12</date><risdate>2024</risdate><volume>20</volume><issue>12</issue><spage>8246</spage><epage>8262</epage><pages>8246-8262</pages><issn>1552-5260</issn><issn>1552-5279</issn><eissn>1552-5279</eissn><abstract>INTRODUCTION
The genetic basis of Alzheimer's disease (AD) in Koreans is poorly understood.
METHODS
We performed an AD genome‐wide association study using whole‐genome sequence data from 3540 Koreans (1583 AD cases, 1957 controls) and single‐nucleotide polymorphism array data from 2978 Japanese (1336 AD cases, 1642 controls). Significant findings were evaluated by pathway enrichment and differential gene expression analysis in brain tissue from controls and AD cases with and without dementia prior to death.
RESULTS
We identified genome‐wide significant associations with APOE in the total sample and ROCK2 (rs76484417, p = 2.71×10−8) among APOE ε4 non‐carriers. A study‐wide significant association was found with aggregated rare variants in MICALL1 (MICAL like 1) (p = 9.04×10−7). Several novel AD‐associated genes, including ROCK2 and MICALL1, were differentially expressed in AD cases compared to controls (p < 3.33×10−3). ROCK2 was also differentially expressed between AD cases with and without dementia (p = 1.34×10−4).
DISCUSSION
Our results provide insight into genetic mechanisms leading to AD and cognitive resilience in East Asians.
Highlights
Novel genome‐wide significant associations for AD identified with ROCK2 and MICALL1.
ROCK2 and MICALL1 are differentially expressed between AD cases and controls in the brain.
This is the largest whole‐genome‐sequence study of AD in an East Asian population.</abstract><cop>United States</cop><pub>John Wiley and Sons Inc</pub><pmid>39428694</pmid><doi>10.1002/alz.14128</doi><tpages>17</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Aged Aged, 80 and over Alzheimer Disease - genetics Alzheimer's disease Apolipoproteins E - genetics differential gene expression East Asian People - genetics Female Genetic Predisposition to Disease gene‐based association Genome-Wide Association Study Humans Male pathway enrichment Polymorphism, Single Nucleotide Republic of Korea rho-Associated Kinases - genetics Whole Genome Sequencing |
| title | Whole‐genome sequencing study in Koreans identifies novel loci for Alzheimer's disease |
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