Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile.

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Kilpeläinen, Tuomas O (author)

Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile.

Article/chapterEnglish2011

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2011-06-26
Springer Science and Business Media LLC,2011

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LIBRIS-ID:oai:gup.ub.gu.se/144667
https://gup.ub.gu.se/publication/144667URI
https://doi.org/10.1038/ng.866DOI
https://lup.lub.lu.se/record/2071861URI
http://kipublications.ki.se/Default.aspx?queryparsed=id:122999383URI
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-157022URI

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Language:English

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SwePubSwePub

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

Genome-wide association studies have identified 32 loci influencing body mass index, but this measure does not distinguish lean from fat mass. To identify adiposity loci, we meta-analyzed associations between ∼2.5 million SNPs and body fat percentage from 36,626 individuals and followed up the 14 most significant (P < 10(-6)) independent loci in 39,576 individuals. We confirmed a previously established adiposity locus in FTO (P = 3 × 10(-26)) and identified two new loci associated with body fat percentage, one near IRS1 (P = 4 × 10(-11)) and one near SPRY2 (P = 3 × 10(-8)). Both loci contain genes with potential links to adipocyte physiology. Notably, the body-fat-decreasing allele near IRS1 is associated with decreased IRS1 expression and with an impaired metabolic profile, including an increased visceral to subcutaneous fat ratio, insulin resistance, dyslipidemia, risk of diabetes and coronary artery disease and decreased adiponectin levels. Our findings provide new insights into adiposity and insulin resistance.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Endokrinologi och diabetes hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Endocrinology and Diabetes hsv//eng
MEDICINE

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Zillikens, M Carola (author)
Stančákova, Alena (author)
Finucane, Francis M (author)
Ried, Janina S (author)
Langenberg, Claudia (author)
Zhang, Weihua (author)
Beckmann, Jacques S (author)
Luan, Jian'an (author)
Vandenput, Liesbeth,1974Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine(Swepub:gu)xvanli (author)
Styrkarsdottir, Unnur (author)
Zhou, Yanhua (author)
Smith, Albert Vernon (author)
Zhao, Jing-Hua (author)
Amin, Najaf (author)
Vedantam, Sailaja (author)
Shin, So-Youn (author)
Haritunians, Talin (author)
Fu, Mao (author)
Feitosa, Mary F (author)
Kumari, Meena (author)
Halldorsson, Bjarni V (author)
Tikkanen, Emmi (author)
Mangino, Massimo (author)
Hayward, Caroline (author)
Song, CiKarolinska Institutet (author)
Arnold, Alice M (author)
Aulchenko, Yurii S (author)
Oostra, Ben A (author)
Campbell, Harry (author)
Cupples, L Adrienne (author)
Davis, Kathryn E (author)
Döring, Angela (author)
Eiriksdottir, Gudny (author)
Estrada, Karol (author)
Fernández-Real, José Manuel (author)
Garcia, Melissa (author)
Gieger, Christian (author)
Glazer, Nicole L (author)
Guiducci, Candace (author)
Hofman, Albert (author)
Humphries, Steve E (author)
Isomaa, Bo (author)
Jacobs, Leonie C (author)
Jula, Antti (author)
Karasik, David (author)
Karlsson, Magnus K.Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Department of Clinical Sciences, Malmö,Faculty of Medicine(Swepub:lu)orto-mka (author)
Khaw, Kay-Tee (author)
Kim, Lauren J (author)
Kivimäki, Mika (author)
Klopp, Norman (author)
Kühnel, Brigitte (author)
Kuusisto, Johanna (author)
Liu, Yongmei (author)
Ljunggren, ÖstenUppsala universitet,Institutionen för medicinska vetenskaper(Swepub:uu)osteljun (author)
Lorentzon, Mattias,1970Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research(Swepub:gu)xlomat (author)
Luben, Robert N (author)
McKnight, Barbara (author)
Mellström, Dan,1945Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research(Swepub:gu)xmelda (author)
Mitchell, Braxton D (author)
Mooser, Vincent (author)
Moreno, José Maria (author)
Männistö, Satu (author)
O'Connell, Jeffery R (author)
Pascoe, Laura (author)
Peltonen, Leena (author)
Peral, Belén (author)
Perola, Markus (author)
Psaty, Bruce M (author)
Salomaa, Veikko (author)
Savage, David B (author)
Semple, Robert K (author)
Skaric-Juric, Tatjana (author)
Sigurdsson, Gunnar (author)
Song, Kijoung S (author)
Spector, Timothy D (author)
Syvänen, Ann-ChristineUppsala universitet,Molekylär medicin,Science for Life Laboratory, SciLifeLab(Swepub:uu)anncsyva (author)
Talmud, Philippa J (author)
Thorleifsson, Gudmar (author)
Thorsteinsdottir, Unnur (author)
Uitterlinden, André G (author)
van Duijn, Cornelia M (author)
Vidal-Puig, Antonio (author)
Wild, Sarah H (author)
Wright, Alan F (author)
Clegg, Deborah J (author)
Schadt, Eric (author)
Wilson, James F (author)
Rudan, Igor (author)
Ripatti, Samuli (author)
Borecki, Ingrid B (author)
Shuldiner, Alan R (author)
Ingelsson, ErikUppsala universitet,Karolinska Institutet,Geriatrik(Swepub:uu)ering425 (author)
Jansson, John-Olov,1954Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology(Swepub:gu)xjanjo (author)
Kaplan, Robert C (author)
Gudnason, Vilmundur (author)
Harris, Tamara B (author)
Groop, LeifLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)endo-lgr (author)
Kiel, Douglas P (author)
Rivadeneira, Fernando (author)
Walker, Mark (author)
Barroso, Inês (author)
Vollenweider, Peter (author)
Waeber, Gérard (author)
Chambers, John C (author)
Kooner, Jaspal S (author)
Soranzo, Nicole (author)
Hirschhorn, Joel N (author)
Stefansson, Kari (author)
Wichmann, H-Erich (author)
Ohlsson, Claes,1965Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine(Swepub:gu)xohlcl (author)
O'Rahilly, Stephen (author)
Wareham, Nicholas J (author)
Speliotes, Elizabeth K (author)
Fox, Caroline S (author)
Laakso, Markku (author)
Loos, Ruth J F (author)
Göteborgs universitetCentre for Bone and Arthritis Research (creator_code:org_t)

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In:Nature genetics: Springer Science and Business Media LLC43:8, s. 753-601546-17181061-4036

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By the author/editor: Kilpeläinen, Tuo ...; Zillikens, M Car ...; Stančákova, Alen ...; Finucane, Franci ...; Ried, Janina S; Langenberg, Clau ...; show more...; Zhang, Weihua; Beckmann, Jacque ...; Luan, Jian'an; Vandenput, Liesb ...; Styrkarsdottir, ...; Zhou, Yanhua; Smith, Albert Ve ...; Zhao, Jing-Hua; Amin, Najaf; Vedantam, Sailaj ...; Shin, So-Youn; Haritunians, Tal ...; Fu, Mao; Feitosa, Mary F; Kumari, Meena; Halldorsson, Bja ...; Tikkanen, Emmi; Mangino, Massimo; Hayward, Carolin ...; Song, Ci; Arnold, Alice M; Aulchenko, Yurii ...; Oostra, Ben A; Campbell, Harry; Cupples, L Adrie ...; Davis, Kathryn E; Döring, Angela; Eiriksdottir, Gu ...; Estrada, Karol; Fernández-Real, ...; Garcia, Melissa; Gieger, Christia ...; Glazer, Nicole L; Guiducci, Candac ...; Hofman, Albert; Humphries, Steve ...; Isomaa, Bo; Jacobs, Leonie C; Jula, Antti; Karasik, David; Karlsson, Magnus ...; Khaw, Kay-Tee; Kim, Lauren J; Kivimäki, Mika; Klopp, Norman; Kühnel, Brigitte; Kuusisto, Johann ...; Liu, Yongmei; Ljunggren, Östen; Lorentzon, Matti ...; Luben, Robert N; McKnight, Barbar ...; Mellström, Dan, ...; Mitchell, Braxto ...; Mooser, Vincent; Moreno, José Mar ...; Männistö, Satu; O'Connell, Jeffe ...; Pascoe, Laura; Peltonen, Leena; Peral, Belén; Perola, Markus; Psaty, Bruce M; Salomaa, Veikko; Savage, David B; Semple, Robert K; Skaric-Juric, Ta ...; Sigurdsson, Gunn ...; Song, Kijoung S; Spector, Timothy ...; Syvänen, Ann-Chr ...; Talmud, Philippa ...; Thorleifsson, Gu ...; Thorsteinsdottir ...; Uitterlinden, An ...; van Duijn, Corne ...; Vidal-Puig, Anto ...; Wild, Sarah H; Wright, Alan F; Clegg, Deborah J; Schadt, Eric; Wilson, James F; Rudan, Igor; Ripatti, Samuli; Borecki, Ingrid ...; Shuldiner, Alan ...; Ingelsson, Erik; Jansson, John-Ol ...; Kaplan, Robert C; Gudnason, Vilmun ...; Harris, Tamara B; Groop, Leif; Kiel, Douglas P; Rivadeneira, Fer ...; Walker, Mark; Barroso, Inês; Vollenweider, Pe ...; Waeber, Gérard; Chambers, John C; Kooner, Jaspal S; Soranzo, Nicole; Hirschhorn, Joel ...; Stefansson, Kari; Wichmann, H-Eric ...; Ohlsson, Claes, ...; O'Rahilly, Steph ...; Wareham, Nichola ...; Speliotes, Eliza ...; Fox, Caroline S; Laakso, Markku; Loos, Ruth J F; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Endocrinology an ...

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