Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels
Variants associated with blood lipid levels may be population-specific. To identify low-frequency variants associated with this phenotype, population-specific reference panels may be used. Here we impute nine large Dutch biobanks (~35,000 samples) with the population-specific reference panel created...
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| Veröffentlicht in: | Nature communications 2015-03, Vol.6 (1), p.6065-6065, Article 6065 |
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| creator | van Leeuwen, Elisabeth M. Karssen, Lennart C. Deelen, Joris Isaacs, Aaron Medina-Gomez, Carolina Mbarek, Hamdi Kanterakis, Alexandros Trompet, Stella Postmus, Iris Verweij, Niek van Enckevort, David J. Huffman, Jennifer E. White, Charles C. Feitosa, Mary F. Bartz, Traci M. Manichaikul, Ani Joshi, Peter K. Peloso, Gina M. Deelen, Patrick van Dijk, Freerk Willemsen, Gonneke de Geus, Eco J. Milaneschi, Yuri Penninx, Brenda W.J.H. Francioli, Laurent C. Menelaou, Androniki Pulit, Sara L. Rivadeneira, Fernando Hofman, Albert Oostra, Ben A. Franco, Oscar H. Leach, Irene Mateo Beekman, Marian de Craen, Anton J.M. Uh, Hae-Won Trochet, Holly Hocking, Lynne J. Porteous, David J. Sattar, Naveed Packard, Chris J. Buckley, Brendan M. Brody, Jennifer A. Bis, Joshua C. Rotter, Jerome I. Mychaleckyj, Josyf C. Campbell, Harry Duan, Qing Lange, Leslie A. Wilson, James F. Hayward, Caroline Polasek, Ozren Vitart, Veronique Rudan, Igor Wright, Alan F. Rich, Stephen S. Psaty, Bruce M. Borecki, Ingrid B. Kearney, Patricia M. Stott, David J. Adrienne Cupples, L. Jukema, J. Wouter van der Harst, Pim Sijbrands, Eric J. Hottenga, Jouke-Jan Uitterlinden, Andre G. Swertz, Morris A. van Ommen, Gert-Jan B. de Bakker, Paul I.W. Eline Slagboom, P. Boomsma, Dorret I. Wijmenga, Cisca van Duijn, Cornelia M. |
| description | Variants associated with blood lipid levels may be population-specific. To identify low-frequency variants associated with this phenotype, population-specific reference panels may be used. Here we impute nine large Dutch biobanks (~35,000 samples) with the population-specific reference panel created by the Genome of the Netherlands Project and perform association testing with blood lipid levels. We report the discovery of five novel associations at four loci (
P
value |
| doi_str_mv | 10.1038/ncomms7065 |
| format | Article |
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Wouter ; van der Harst, Pim ; Sijbrands, Eric J. ; Hottenga, Jouke-Jan ; Uitterlinden, Andre G. ; Swertz, Morris A. ; van Ommen, Gert-Jan B. ; de Bakker, Paul I.W. ; Eline Slagboom, P. ; Boomsma, Dorret I. ; Wijmenga, Cisca ; van Duijn, Cornelia M.</creator><creatorcontrib>van Leeuwen, Elisabeth M. ; Karssen, Lennart C. ; Deelen, Joris ; Isaacs, Aaron ; Medina-Gomez, Carolina ; Mbarek, Hamdi ; Kanterakis, Alexandros ; Trompet, Stella ; Postmus, Iris ; Verweij, Niek ; van Enckevort, David J. ; Huffman, Jennifer E. ; White, Charles C. ; Feitosa, Mary F. ; Bartz, Traci M. ; Manichaikul, Ani ; Joshi, Peter K. ; Peloso, Gina M. ; Deelen, Patrick ; van Dijk, Freerk ; Willemsen, Gonneke ; de Geus, Eco J. ; Milaneschi, Yuri ; Penninx, Brenda W.J.H. ; Francioli, Laurent C. ; Menelaou, Androniki ; Pulit, Sara L. ; Rivadeneira, Fernando ; Hofman, Albert ; Oostra, Ben A. ; Franco, Oscar H. ; Leach, Irene Mateo ; Beekman, Marian ; de Craen, Anton J.M. ; Uh, Hae-Won ; Trochet, Holly ; Hocking, Lynne J. ; Porteous, David J. ; Sattar, Naveed ; Packard, Chris J. ; Buckley, Brendan M. ; Brody, Jennifer A. ; Bis, Joshua C. ; Rotter, Jerome I. ; Mychaleckyj, Josyf C. ; Campbell, Harry ; Duan, Qing ; Lange, Leslie A. ; Wilson, James F. ; Hayward, Caroline ; Polasek, Ozren ; Vitart, Veronique ; Rudan, Igor ; Wright, Alan F. ; Rich, Stephen S. ; Psaty, Bruce M. ; Borecki, Ingrid B. ; Kearney, Patricia M. ; Stott, David J. ; Adrienne Cupples, L. ; Jukema, J. Wouter ; van der Harst, Pim ; Sijbrands, Eric J. ; Hottenga, Jouke-Jan ; Uitterlinden, Andre G. ; Swertz, Morris A. ; van Ommen, Gert-Jan B. ; de Bakker, Paul I.W. ; Eline Slagboom, P. ; Boomsma, Dorret I. ; Wijmenga, Cisca ; van Duijn, Cornelia M. ; Genome of The Netherlands Consortium ; The Genome of the Netherlands Consortium</creatorcontrib><description>Variants associated with blood lipid levels may be population-specific. To identify low-frequency variants associated with this phenotype, population-specific reference panels may be used. Here we impute nine large Dutch biobanks (~35,000 samples) with the population-specific reference panel created by the Genome of the Netherlands Project and perform association testing with blood lipid levels. We report the discovery of five novel associations at four loci (
P
value <6.61 × 10
−4
), including a rare missense variant in
ABCA6
(rs77542162, p.Cys1359Arg, frequency 0.034), which is predicted to be deleterious. The frequency of this
ABCA6
variant is 3.65-fold increased in the Dutch and its effect (
β
LDL-C
=0.135,
β
TC
=0.140) is estimated to be very similar to those observed for single variants in well-known lipid genes, such as
LDLR
.
Frequencies of rare variants fluctuate over populations, hampering gene discovery. Here the authors use a population-specific reference panel, the Genome of the Netherlands, to discover four novel loci involved in lipid metabolism, including an exonic variant in
ABCA6
.</description><identifier>ISSN: 2041-1723</identifier><identifier>EISSN: 2041-1723</identifier><identifier>DOI: 10.1038/ncomms7065</identifier><identifier>PMID: 25751400</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/208/205/2138 ; 631/208/457/649/2219 ; 631/45/287 ; ATP-Binding Cassette Transporters - genetics ; Cholesterol - blood ; Gene Frequency ; Genetic Association Studies ; Humanities and Social Sciences ; Humans ; multidisciplinary ; Mutation, Missense - genetics ; Netherlands ; Science ; Science (multidisciplinary)</subject><ispartof>Nature communications, 2015-03, Vol.6 (1), p.6065-6065, Article 6065</ispartof><rights>The Author(s) 2015</rights><rights>Copyright Nature Publishing Group Mar 2015</rights><rights>Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. 2015 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c442t-b8c9ebde3147489add023fbe525a31e4a5a3e6a8aa0619985bce65b1abc9e3ac3</citedby><cites>FETCH-LOGICAL-c442t-b8c9ebde3147489add023fbe525a31e4a5a3e6a8aa0619985bce65b1abc9e3ac3</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/PMC4366498/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4366498/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,27929,27930,41125,42194,51581,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25751400$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>van Leeuwen, Elisabeth M.</creatorcontrib><creatorcontrib>Karssen, Lennart C.</creatorcontrib><creatorcontrib>Deelen, Joris</creatorcontrib><creatorcontrib>Isaacs, Aaron</creatorcontrib><creatorcontrib>Medina-Gomez, Carolina</creatorcontrib><creatorcontrib>Mbarek, Hamdi</creatorcontrib><creatorcontrib>Kanterakis, Alexandros</creatorcontrib><creatorcontrib>Trompet, Stella</creatorcontrib><creatorcontrib>Postmus, Iris</creatorcontrib><creatorcontrib>Verweij, Niek</creatorcontrib><creatorcontrib>van Enckevort, David J.</creatorcontrib><creatorcontrib>Huffman, Jennifer E.</creatorcontrib><creatorcontrib>White, Charles C.</creatorcontrib><creatorcontrib>Feitosa, Mary F.</creatorcontrib><creatorcontrib>Bartz, Traci M.</creatorcontrib><creatorcontrib>Manichaikul, Ani</creatorcontrib><creatorcontrib>Joshi, Peter K.</creatorcontrib><creatorcontrib>Peloso, Gina M.</creatorcontrib><creatorcontrib>Deelen, Patrick</creatorcontrib><creatorcontrib>van Dijk, Freerk</creatorcontrib><creatorcontrib>Willemsen, Gonneke</creatorcontrib><creatorcontrib>de Geus, Eco J.</creatorcontrib><creatorcontrib>Milaneschi, Yuri</creatorcontrib><creatorcontrib>Penninx, Brenda W.J.H.</creatorcontrib><creatorcontrib>Francioli, Laurent C.</creatorcontrib><creatorcontrib>Menelaou, Androniki</creatorcontrib><creatorcontrib>Pulit, Sara L.</creatorcontrib><creatorcontrib>Rivadeneira, Fernando</creatorcontrib><creatorcontrib>Hofman, Albert</creatorcontrib><creatorcontrib>Oostra, Ben A.</creatorcontrib><creatorcontrib>Franco, Oscar H.</creatorcontrib><creatorcontrib>Leach, Irene Mateo</creatorcontrib><creatorcontrib>Beekman, Marian</creatorcontrib><creatorcontrib>de Craen, Anton J.M.</creatorcontrib><creatorcontrib>Uh, Hae-Won</creatorcontrib><creatorcontrib>Trochet, Holly</creatorcontrib><creatorcontrib>Hocking, Lynne J.</creatorcontrib><creatorcontrib>Porteous, David J.</creatorcontrib><creatorcontrib>Sattar, Naveed</creatorcontrib><creatorcontrib>Packard, Chris J.</creatorcontrib><creatorcontrib>Buckley, Brendan M.</creatorcontrib><creatorcontrib>Brody, Jennifer A.</creatorcontrib><creatorcontrib>Bis, Joshua C.</creatorcontrib><creatorcontrib>Rotter, Jerome I.</creatorcontrib><creatorcontrib>Mychaleckyj, Josyf C.</creatorcontrib><creatorcontrib>Campbell, Harry</creatorcontrib><creatorcontrib>Duan, Qing</creatorcontrib><creatorcontrib>Lange, Leslie A.</creatorcontrib><creatorcontrib>Wilson, James F.</creatorcontrib><creatorcontrib>Hayward, Caroline</creatorcontrib><creatorcontrib>Polasek, Ozren</creatorcontrib><creatorcontrib>Vitart, Veronique</creatorcontrib><creatorcontrib>Rudan, Igor</creatorcontrib><creatorcontrib>Wright, Alan F.</creatorcontrib><creatorcontrib>Rich, Stephen S.</creatorcontrib><creatorcontrib>Psaty, Bruce M.</creatorcontrib><creatorcontrib>Borecki, Ingrid B.</creatorcontrib><creatorcontrib>Kearney, Patricia M.</creatorcontrib><creatorcontrib>Stott, David J.</creatorcontrib><creatorcontrib>Adrienne Cupples, L.</creatorcontrib><creatorcontrib>Jukema, J. Wouter</creatorcontrib><creatorcontrib>van der Harst, Pim</creatorcontrib><creatorcontrib>Sijbrands, Eric J.</creatorcontrib><creatorcontrib>Hottenga, Jouke-Jan</creatorcontrib><creatorcontrib>Uitterlinden, Andre G.</creatorcontrib><creatorcontrib>Swertz, Morris A.</creatorcontrib><creatorcontrib>van Ommen, Gert-Jan B.</creatorcontrib><creatorcontrib>de Bakker, Paul I.W.</creatorcontrib><creatorcontrib>Eline Slagboom, P.</creatorcontrib><creatorcontrib>Boomsma, Dorret I.</creatorcontrib><creatorcontrib>Wijmenga, Cisca</creatorcontrib><creatorcontrib>van Duijn, Cornelia M.</creatorcontrib><creatorcontrib>Genome of The Netherlands Consortium</creatorcontrib><creatorcontrib>The Genome of the Netherlands Consortium</creatorcontrib><title>Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels</title><title>Nature communications</title><addtitle>Nat Commun</addtitle><addtitle>Nat Commun</addtitle><description>Variants associated with blood lipid levels may be population-specific. To identify low-frequency variants associated with this phenotype, population-specific reference panels may be used. Here we impute nine large Dutch biobanks (~35,000 samples) with the population-specific reference panel created by the Genome of the Netherlands Project and perform association testing with blood lipid levels. We report the discovery of five novel associations at four loci (
P
value <6.61 × 10
−4
), including a rare missense variant in
ABCA6
(rs77542162, p.Cys1359Arg, frequency 0.034), which is predicted to be deleterious. The frequency of this
ABCA6
variant is 3.65-fold increased in the Dutch and its effect (
β
LDL-C
=0.135,
β
TC
=0.140) is estimated to be very similar to those observed for single variants in well-known lipid genes, such as
LDLR
.
Frequencies of rare variants fluctuate over populations, hampering gene discovery. Here the authors use a population-specific reference panel, the Genome of the Netherlands, to discover four novel loci involved in lipid metabolism, including an exonic variant in
ABCA6
.</description><subject>631/208/205/2138</subject><subject>631/208/457/649/2219</subject><subject>631/45/287</subject><subject>ATP-Binding Cassette Transporters - genetics</subject><subject>Cholesterol - blood</subject><subject>Gene Frequency</subject><subject>Genetic Association Studies</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>multidisciplinary</subject><subject>Mutation, Missense - genetics</subject><subject>Netherlands</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><issn>2041-1723</issn><issn>2041-1723</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNplkU1v1DAQhi1ERaulF34AssQFFQXs2M7HBWlZQVupggucrYkz6bpy7GAni_rv63ZLWcAHj-V55vU7HkJecfaeM9F88CaMY6pZpZ6Rk5JJXvC6FM8PzsfkNKUblpdoeSPlC3JcqlpxydgJ2Z2jDyPSMNB5i_Qr5j068H2iU5gWB7MNvkgTGjtYQ-04LfPDXaK2Rz_b4ZaCp-tPm3VFdxAt-JlCSsFYmLGnv-y8pWYbHKYZY3DU4Q5dekmOBnAJTx_jivz48vn75qK4-nZ-uVlfFUbKci66xrTY9Si4rGXTQt-zUgwdqlKB4CghB6ygAWAVb9tGdQYr1XHocp0AI1bk4153WroRe5MdR3B6inaEeKsDWP13xtutvg47LUVVybbJAm8fBWL4ueQm9GiTQZe_CMOSNK-qUgqusq8VefMPehOW6HN79xSv61ZylamzPWViSCni8GSGM30_Uf1nohl-fWj_Cf09vwy82wMpp_w1xoM3_5e7Ax0BryY</recordid><startdate>20150309</startdate><enddate>20150309</enddate><creator>van Leeuwen, Elisabeth M.</creator><creator>Karssen, Lennart C.</creator><creator>Deelen, Joris</creator><creator>Isaacs, Aaron</creator><creator>Medina-Gomez, Carolina</creator><creator>Mbarek, Hamdi</creator><creator>Kanterakis, Alexandros</creator><creator>Trompet, Stella</creator><creator>Postmus, Iris</creator><creator>Verweij, Niek</creator><creator>van Enckevort, David J.</creator><creator>Huffman, Jennifer E.</creator><creator>White, Charles C.</creator><creator>Feitosa, Mary F.</creator><creator>Bartz, Traci M.</creator><creator>Manichaikul, Ani</creator><creator>Joshi, Peter K.</creator><creator>Peloso, Gina M.</creator><creator>Deelen, Patrick</creator><creator>van Dijk, Freerk</creator><creator>Willemsen, Gonneke</creator><creator>de Geus, Eco J.</creator><creator>Milaneschi, Yuri</creator><creator>Penninx, Brenda W.J.H.</creator><creator>Francioli, Laurent C.</creator><creator>Menelaou, Androniki</creator><creator>Pulit, Sara L.</creator><creator>Rivadeneira, Fernando</creator><creator>Hofman, Albert</creator><creator>Oostra, Ben A.</creator><creator>Franco, Oscar H.</creator><creator>Leach, Irene Mateo</creator><creator>Beekman, Marian</creator><creator>de Craen, Anton J.M.</creator><creator>Uh, Hae-Won</creator><creator>Trochet, Holly</creator><creator>Hocking, Lynne J.</creator><creator>Porteous, David J.</creator><creator>Sattar, Naveed</creator><creator>Packard, Chris J.</creator><creator>Buckley, Brendan M.</creator><creator>Brody, Jennifer A.</creator><creator>Bis, Joshua C.</creator><creator>Rotter, Jerome I.</creator><creator>Mychaleckyj, Josyf C.</creator><creator>Campbell, Harry</creator><creator>Duan, Qing</creator><creator>Lange, Leslie A.</creator><creator>Wilson, James F.</creator><creator>Hayward, Caroline</creator><creator>Polasek, Ozren</creator><creator>Vitart, Veronique</creator><creator>Rudan, Igor</creator><creator>Wright, Alan F.</creator><creator>Rich, Stephen S.</creator><creator>Psaty, Bruce M.</creator><creator>Borecki, Ingrid B.</creator><creator>Kearney, Patricia M.</creator><creator>Stott, David J.</creator><creator>Adrienne Cupples, L.</creator><creator>Jukema, J. 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Group</general><scope>C6C</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>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7ST</scope><scope>7T5</scope><scope>7T7</scope><scope>7TM</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>SOI</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20150309</creationdate><title>Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels</title><author>van Leeuwen, Elisabeth M. ; Karssen, Lennart C. ; Deelen, Joris ; Isaacs, Aaron ; Medina-Gomez, Carolina ; Mbarek, Hamdi ; Kanterakis, Alexandros ; Trompet, Stella ; Postmus, Iris ; Verweij, Niek ; van Enckevort, David J. ; Huffman, Jennifer E. ; White, Charles C. ; Feitosa, Mary F. ; Bartz, Traci M. ; Manichaikul, Ani ; Joshi, Peter K. ; Peloso, Gina M. ; Deelen, Patrick ; van Dijk, Freerk ; Willemsen, Gonneke ; de Geus, Eco J. ; Milaneschi, Yuri ; Penninx, Brenda W.J.H. ; Francioli, Laurent C. ; Menelaou, Androniki ; Pulit, Sara L. ; Rivadeneira, Fernando ; Hofman, Albert ; Oostra, Ben A. ; Franco, Oscar H. ; Leach, Irene Mateo ; Beekman, Marian ; de Craen, Anton J.M. ; Uh, Hae-Won ; Trochet, Holly ; Hocking, Lynne J. ; Porteous, David J. ; Sattar, Naveed ; Packard, Chris J. ; Buckley, Brendan M. ; Brody, Jennifer A. ; Bis, Joshua C. ; Rotter, Jerome I. ; Mychaleckyj, Josyf C. ; Campbell, Harry ; Duan, Qing ; Lange, Leslie A. ; Wilson, James F. ; Hayward, Caroline ; Polasek, Ozren ; Vitart, Veronique ; Rudan, Igor ; Wright, Alan F. ; Rich, Stephen S. ; Psaty, Bruce M. ; Borecki, Ingrid B. ; Kearney, Patricia M. ; Stott, David J. ; Adrienne Cupples, L. ; Jukema, J. Wouter ; van der Harst, Pim ; Sijbrands, Eric J. ; Hottenga, Jouke-Jan ; Uitterlinden, Andre G. ; Swertz, Morris A. ; van Ommen, Gert-Jan B. ; de Bakker, Paul I.W. ; Eline Slagboom, P. ; Boomsma, Dorret I. ; Wijmenga, Cisca ; van Duijn, Cornelia M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c442t-b8c9ebde3147489add023fbe525a31e4a5a3e6a8aa0619985bce65b1abc9e3ac3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>631/208/205/2138</topic><topic>631/208/457/649/2219</topic><topic>631/45/287</topic><topic>ATP-Binding Cassette Transporters - genetics</topic><topic>Cholesterol - blood</topic><topic>Gene Frequency</topic><topic>Genetic Association Studies</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>multidisciplinary</topic><topic>Mutation, Missense - genetics</topic><topic>Netherlands</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>van Leeuwen, Elisabeth M.</creatorcontrib><creatorcontrib>Karssen, Lennart C.</creatorcontrib><creatorcontrib>Deelen, Joris</creatorcontrib><creatorcontrib>Isaacs, Aaron</creatorcontrib><creatorcontrib>Medina-Gomez, Carolina</creatorcontrib><creatorcontrib>Mbarek, Hamdi</creatorcontrib><creatorcontrib>Kanterakis, Alexandros</creatorcontrib><creatorcontrib>Trompet, Stella</creatorcontrib><creatorcontrib>Postmus, Iris</creatorcontrib><creatorcontrib>Verweij, Niek</creatorcontrib><creatorcontrib>van Enckevort, David J.</creatorcontrib><creatorcontrib>Huffman, Jennifer E.</creatorcontrib><creatorcontrib>White, Charles C.</creatorcontrib><creatorcontrib>Feitosa, Mary F.</creatorcontrib><creatorcontrib>Bartz, Traci M.</creatorcontrib><creatorcontrib>Manichaikul, Ani</creatorcontrib><creatorcontrib>Joshi, Peter K.</creatorcontrib><creatorcontrib>Peloso, Gina M.</creatorcontrib><creatorcontrib>Deelen, Patrick</creatorcontrib><creatorcontrib>van Dijk, Freerk</creatorcontrib><creatorcontrib>Willemsen, Gonneke</creatorcontrib><creatorcontrib>de Geus, Eco J.</creatorcontrib><creatorcontrib>Milaneschi, Yuri</creatorcontrib><creatorcontrib>Penninx, Brenda W.J.H.</creatorcontrib><creatorcontrib>Francioli, Laurent C.</creatorcontrib><creatorcontrib>Menelaou, Androniki</creatorcontrib><creatorcontrib>Pulit, Sara L.</creatorcontrib><creatorcontrib>Rivadeneira, Fernando</creatorcontrib><creatorcontrib>Hofman, Albert</creatorcontrib><creatorcontrib>Oostra, Ben A.</creatorcontrib><creatorcontrib>Franco, Oscar H.</creatorcontrib><creatorcontrib>Leach, Irene Mateo</creatorcontrib><creatorcontrib>Beekman, Marian</creatorcontrib><creatorcontrib>de Craen, Anton J.M.</creatorcontrib><creatorcontrib>Uh, Hae-Won</creatorcontrib><creatorcontrib>Trochet, Holly</creatorcontrib><creatorcontrib>Hocking, Lynne J.</creatorcontrib><creatorcontrib>Porteous, David J.</creatorcontrib><creatorcontrib>Sattar, Naveed</creatorcontrib><creatorcontrib>Packard, Chris J.</creatorcontrib><creatorcontrib>Buckley, Brendan M.</creatorcontrib><creatorcontrib>Brody, Jennifer A.</creatorcontrib><creatorcontrib>Bis, Joshua C.</creatorcontrib><creatorcontrib>Rotter, Jerome I.</creatorcontrib><creatorcontrib>Mychaleckyj, Josyf C.</creatorcontrib><creatorcontrib>Campbell, Harry</creatorcontrib><creatorcontrib>Duan, Qing</creatorcontrib><creatorcontrib>Lange, Leslie A.</creatorcontrib><creatorcontrib>Wilson, James F.</creatorcontrib><creatorcontrib>Hayward, Caroline</creatorcontrib><creatorcontrib>Polasek, Ozren</creatorcontrib><creatorcontrib>Vitart, Veronique</creatorcontrib><creatorcontrib>Rudan, Igor</creatorcontrib><creatorcontrib>Wright, Alan F.</creatorcontrib><creatorcontrib>Rich, Stephen S.</creatorcontrib><creatorcontrib>Psaty, Bruce M.</creatorcontrib><creatorcontrib>Borecki, Ingrid B.</creatorcontrib><creatorcontrib>Kearney, Patricia M.</creatorcontrib><creatorcontrib>Stott, David J.</creatorcontrib><creatorcontrib>Adrienne Cupples, L.</creatorcontrib><creatorcontrib>Jukema, J. Wouter</creatorcontrib><creatorcontrib>van der Harst, Pim</creatorcontrib><creatorcontrib>Sijbrands, Eric J.</creatorcontrib><creatorcontrib>Hottenga, Jouke-Jan</creatorcontrib><creatorcontrib>Uitterlinden, Andre G.</creatorcontrib><creatorcontrib>Swertz, Morris A.</creatorcontrib><creatorcontrib>van Ommen, Gert-Jan B.</creatorcontrib><creatorcontrib>de Bakker, Paul I.W.</creatorcontrib><creatorcontrib>Eline Slagboom, P.</creatorcontrib><creatorcontrib>Boomsma, Dorret I.</creatorcontrib><creatorcontrib>Wijmenga, Cisca</creatorcontrib><creatorcontrib>van Duijn, Cornelia M.</creatorcontrib><creatorcontrib>Genome of The Netherlands Consortium</creatorcontrib><creatorcontrib>The Genome of the Netherlands Consortium</creatorcontrib><collection>Springer Nature OA/Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Environment Abstracts</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>Environment Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nature communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>van Leeuwen, Elisabeth M.</au><au>Karssen, Lennart C.</au><au>Deelen, Joris</au><au>Isaacs, Aaron</au><au>Medina-Gomez, Carolina</au><au>Mbarek, Hamdi</au><au>Kanterakis, Alexandros</au><au>Trompet, Stella</au><au>Postmus, Iris</au><au>Verweij, Niek</au><au>van Enckevort, David J.</au><au>Huffman, Jennifer E.</au><au>White, Charles C.</au><au>Feitosa, Mary F.</au><au>Bartz, Traci M.</au><au>Manichaikul, Ani</au><au>Joshi, Peter K.</au><au>Peloso, Gina M.</au><au>Deelen, Patrick</au><au>van Dijk, Freerk</au><au>Willemsen, Gonneke</au><au>de Geus, Eco J.</au><au>Milaneschi, Yuri</au><au>Penninx, Brenda W.J.H.</au><au>Francioli, Laurent C.</au><au>Menelaou, Androniki</au><au>Pulit, Sara L.</au><au>Rivadeneira, Fernando</au><au>Hofman, Albert</au><au>Oostra, Ben A.</au><au>Franco, Oscar H.</au><au>Leach, Irene Mateo</au><au>Beekman, Marian</au><au>de Craen, Anton J.M.</au><au>Uh, Hae-Won</au><au>Trochet, Holly</au><au>Hocking, Lynne J.</au><au>Porteous, David J.</au><au>Sattar, Naveed</au><au>Packard, Chris J.</au><au>Buckley, Brendan M.</au><au>Brody, Jennifer A.</au><au>Bis, Joshua C.</au><au>Rotter, Jerome I.</au><au>Mychaleckyj, Josyf C.</au><au>Campbell, Harry</au><au>Duan, Qing</au><au>Lange, Leslie A.</au><au>Wilson, James F.</au><au>Hayward, Caroline</au><au>Polasek, Ozren</au><au>Vitart, Veronique</au><au>Rudan, Igor</au><au>Wright, Alan F.</au><au>Rich, Stephen S.</au><au>Psaty, Bruce M.</au><au>Borecki, Ingrid B.</au><au>Kearney, Patricia M.</au><au>Stott, David J.</au><au>Adrienne Cupples, L.</au><au>Jukema, J. Wouter</au><au>van der Harst, Pim</au><au>Sijbrands, Eric J.</au><au>Hottenga, Jouke-Jan</au><au>Uitterlinden, Andre G.</au><au>Swertz, Morris A.</au><au>van Ommen, Gert-Jan B.</au><au>de Bakker, Paul I.W.</au><au>Eline Slagboom, P.</au><au>Boomsma, Dorret I.</au><au>Wijmenga, Cisca</au><au>van Duijn, Cornelia M.</au><aucorp>Genome of The Netherlands Consortium</aucorp><aucorp>The Genome of the Netherlands Consortium</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels</atitle><jtitle>Nature communications</jtitle><stitle>Nat Commun</stitle><addtitle>Nat Commun</addtitle><date>2015-03-09</date><risdate>2015</risdate><volume>6</volume><issue>1</issue><spage>6065</spage><epage>6065</epage><pages>6065-6065</pages><artnum>6065</artnum><issn>2041-1723</issn><eissn>2041-1723</eissn><abstract>Variants associated with blood lipid levels may be population-specific. To identify low-frequency variants associated with this phenotype, population-specific reference panels may be used. Here we impute nine large Dutch biobanks (~35,000 samples) with the population-specific reference panel created by the Genome of the Netherlands Project and perform association testing with blood lipid levels. We report the discovery of five novel associations at four loci (
P
value <6.61 × 10
−4
), including a rare missense variant in
ABCA6
(rs77542162, p.Cys1359Arg, frequency 0.034), which is predicted to be deleterious. The frequency of this
ABCA6
variant is 3.65-fold increased in the Dutch and its effect (
β
LDL-C
=0.135,
β
TC
=0.140) is estimated to be very similar to those observed for single variants in well-known lipid genes, such as
LDLR
.
Frequencies of rare variants fluctuate over populations, hampering gene discovery. Here the authors use a population-specific reference panel, the Genome of the Netherlands, to discover four novel loci involved in lipid metabolism, including an exonic variant in
ABCA6
.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>25751400</pmid><doi>10.1038/ncomms7065</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2041-1723 |
| ispartof | Nature communications, 2015-03, Vol.6 (1), p.6065-6065, Article 6065 |
| issn | 2041-1723 2041-1723 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4366498 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Nature Free; PubMed Central; Alma/SFX Local Collection; Springer Nature OA/Free Journals |
| subjects | 631/208/205/2138 631/208/457/649/2219 631/45/287 ATP-Binding Cassette Transporters - genetics Cholesterol - blood Gene Frequency Genetic Association Studies Humanities and Social Sciences Humans multidisciplinary Mutation, Missense - genetics Netherlands Science Science (multidisciplinary) |
| title | Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels |
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