Contribution of common non-synonymous variants in PCSK1 to body mass index variation and risk of obesity: a systematic review and meta-analysis with evidence from up to 331 175 individuals

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Nead, Kevin T. (author)

Contribution of common non-synonymous variants in PCSK1 to body mass index variation and risk of obesity : a systematic review and meta-analysis with evidence from up to 331 175 individuals

Article/chapterEnglish2015

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2015-03-17
Oxford University Press (OUP),2015
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LIBRIS-ID:oai:DiVA.org:uu-256992
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-256992URI
https://doi.org/10.1093/hmg/ddv097DOI
https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-106491URI

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Language:English
Summary in:English

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Subject category:art swepub-publicationtype

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Polymorphisms rs6232 and rs6234/rs6235 in PCSK1 have been associated with extreme obesity [e.g. body mass index (BMI) a parts per thousand yen 40 kg/m(2)], but their contribution to common obesity (BMI a parts per thousand yen 30 kg/m(2)) and BMI variation in a multi-ethnic context is unclear. To fill this gap, we collected phenotypic and genetic data in up to 331 175 individuals from diverse ethnic groups. This process involved a systematic review of the literature in PubMed, Web of Science, Embase and the NIH GWAS catalog complemented by data extraction from pre-existing GWAS or custom-arrays in consortia and single studies. We employed recently developed global meta-analytic random-effects methods to calculate summary odds ratios (OR) and 95% confidence intervals (CIs) or beta estimates and standard errors (SE) for the obesity status and BMI analyses, respectively. Significant associations were found with binary obesity status for rs6232 (OR = 1.15, 95% CI 1.06-1.24, P = 6.08 x 10(-6)) and rs6234/rs6235 (OR = 1.07, 95% CI 1.04-1.10, P = 3.00 x 10(-7)). Similarly, significant associations were found with continuous BMI for rs6232 (beta = 0.03, 95% CI 0.00-0.07; P = 0.047) and rs6234/rs6235 (beta = 0.02, 95% CI 0.00-0.03; P = 5.57 x 10(-4)). Ethnicity, age and study ascertainment significantly modulated the association of PCSK1 polymorphisms with obesity. In summary, we demonstrate evidence that common gene variation in PCSK1 contributes to BMI variation and susceptibility to common obesity in the largest known meta-analysis published to date in genetic epidemiology.

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Li, Aihua (author)
Wehner, Mackenzie R. (author)
Neupane, Binod (author)
Gustafsson, Stefan (author)
Butterworth, Adam (author)
Engert, James C. (author)
Davis, A. Darlene (author)
Hegele, Robert A.Uppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab (author)
Miller, Ruby (author)
den Hoed, Marcel (author)
Khaw, Kay-Tee (author)
Kilpelaeinen, Tuomas O. (author)
Wareham, Nick (author)
Edwards, Todd L. (author)
Hallmans, GoeranUmeå universitet,Enheten för biobanksforskning,Näringsforskning (author)
Varga, Tibor V.Uppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab (author)
Kardia, Sharon L. R. (author)
Smith, Jennifer A. (author)
Zhao, Wei (author)
Faul, Jessica D. (author)
Weir, David (author)
Mi, JieUmeå universitet,Institutionen för folkhälsa och klinisk medicin (author)
Xi, Bo (author)
Quinteros, Samuel Canizales (author)
Cooper, Cyrus (author)
Sayer, Avan Aihie (author)
Jameson, Karen (author)
Grontved, Anders (author)
Fornage, Myriam (author)
Sidney, Stephen (author)
Hanis, Craig L. (author)
Highland, Heather M. (author)
Haering, Hans-Ulrich (author)
Heni, Martin (author)
Lasky-Su, Jessica (author)
Weiss, Scott T. (author)
Gerhard, Glenn S. (author)
Still, Christopher (author)
Melka, Melkaey M. (author)
Pausova, Zdenka (author)
Paus, Tomas (author)
Grant, Struan F. A. (author)
Hakonarson, Hakon (author)
Price, R. Arlen (author)
Wang, Kai (author)
Scherag, Andre (author)
Hebebrand, Johannes (author)
Hinney, Anke (author)
Franks, Paul W. (author)
Frayling, Timothy M. (author)
McCarthy, Mark I. (author)
Hirschhorn, Joel N. (author)
Loos, Ruth J. (author)
Ingelsson, Erik (author)
Gerstein, Hertzel C. (author)
Yusuf, Salim (author)
Beyene, Joseph (author)
Anand, Sonia S. (author)
Meyre, David (author)
Uppsala universitetMolekylär epidemiologi (creator_code:org_t)

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In:Human Molecular Genetics: Oxford University Press (OUP)24:12, s. 3582-35940964-69061460-2083

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By the author/editor: Nead, Kevin T.; Li, Aihua; Wehner, Mackenzi ...; Neupane, Binod; Gustafsson, Stef ...; Butterworth, Ada ...; show more...; Engert, James C.; Davis, A. Darlen ...; Hegele, Robert A ...; Miller, Ruby; den Hoed, Marcel; Khaw, Kay-Tee; Kilpelaeinen, Tu ...; Wareham, Nick; Edwards, Todd L.; Hallmans, Goeran; Varga, Tibor V.; Kardia, Sharon L ...; Smith, Jennifer ...; Zhao, Wei; Faul, Jessica D.; Weir, David; Mi, Jie; Xi, Bo; Quinteros, Samue ...; Cooper, Cyrus; Sayer, Avan Aihi ...; Jameson, Karen; Grontved, Anders; Fornage, Myriam; Sidney, Stephen; Hanis, Craig L.; Highland, Heathe ...; Haering, Hans-Ul ...; Heni, Martin; Lasky-Su, Jessic ...; Weiss, Scott T.; Gerhard, Glenn S ...; Still, Christoph ...; Melka, Melkaey M ...; Pausova, Zdenka; Paus, Tomas; Grant, Struan F. ...; Hakonarson, Hako ...; Price, R. Arlen; Wang, Kai; Scherag, Andre; Hebebrand, Johan ...; Hinney, Anke; Franks, Paul W.; Frayling, Timoth ...; McCarthy, Mark I ...; Hirschhorn, Joel ...; Loos, Ruth J.; Ingelsson, Erik; Gerstein, Hertze ...; Yusuf, Salim; Beyene, Joseph; Anand, Sonia S.; Meyre, David; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Medical Biotechn ...; and Medical Biotechn ...

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