Evidence map›Paper›PMID 25784503›Full record

SynthesisHuman molecular genetics2015

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.

Kevin T Nead, Aihua Li, Mackenzie R Wehner, Binod Neupane, Stefan Gustafsson, Adam Butterworth, James C Engert, A Darlene Davis, Robert A Hegele, Ruby Miller and 51 more

Open access · bronzeAbstract readMeta-AnalysisSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 2 pooled it
5.4field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

34 citing papers in PubMed, 2 syntheses or guidelines pooled it, 66 citations in OpenAlex.

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  12. Genetics, pharmacotherapy, and dietary interventions in childhood obesity.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

61 authors at 20 institutions in 8 countries.

Kevin T NeadDepartment of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA.
Aihua LiDepartment of Clinical Epidemiology and Biostatistics.
Mackenzie R WehnerStanford University School of Medicine, Stanford University, Stanford, CA 94305, USA.
Binod NeupaneDepartment of Clinical Epidemiology and Biostatistics.
Stefan GustafssonDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Adam ButterworthDepartment of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
James C EngertPopulation Health Research Institute, McMaster University, and Hamilton Health Sciences, Hamilton General Hospital, Hamilton, ON, Canada L8L 2X.
A Darlene DavisDepartment of Medicine.
Robert A HegeleDepartment of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada L8S 4L8, Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala SE 751 05, Sweden.
Ruby MillerDepartment of Medicine.
Marcel den HoedThe Research Institute of the McGill University Health Centre, McGill University, Montreal, QC, Canada H3H 2R9, Six Nations Health Services, Ohsweken, Canada N0A 1M0.
Kay-Tee KhawDepartment of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
Tuomas O KilpeläinenThe Research Institute of the McGill University Health Centre, McGill University, Montreal, QC, Canada H3H 2R9, Blackburn Cardiovascular Genetics Laboratory, Robarts Research Institute, London, ON, Canada N6A 5K8.
Nick WarehamThe Research Institute of the McGill University Health Centre, McGill University, Montreal, QC, Canada H3H 2R9.
Todd L EdwardsDepartment of Medicine, University of Western Ontario, London, ON, Canada N6A 3K7.
Göran HallmansMRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
Tibor V VargaDepartment of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Sharon L R KardiaThe Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, University of Copenhagen, Copenhagen 2100, Denmark.
Jennifer A SmithThe Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, University of Copenhagen, Copenhagen 2100, Denmark.
Wei ZhaoThe Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, University of Copenhagen, Copenhagen 2100, Denmark.
Jessica D FaulCenter for Human Genetics Research, Vanderbilt Epidemiology Center, Department of Medicine, Vanderbilt University, Nashville, TN 37235, USA.
David WeirCenter for Human Genetics Research, Vanderbilt Epidemiology Center, Department of Medicine, Vanderbilt University, Nashville, TN 37235, USA.
Jie MiDepartment of Public Health and Clinical Medicine, Umeå University, Umeå 901 87, Sweden.
Bo XiDepartment of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Skåne University Hospital Malmö, Malmö 205 02, Sweden.
Samuel Canizales QuinterosDepartment of Epidemiology, University of Michigan, Ann Arbor, MI 48109, USA.
Cyrus CooperInstitute for Social Research, University of Michigan, Ann Arbor, MI 48104, USA, Department of Epidemiology, Capital Institute of Pediatrics, Beijing 100020, China, Department of Maternal and Child Health Care, School of Public Health, Shandong University, Jinan 250100, China.
Avan Aihie SayerInstitute for Social Research, University of Michigan, Ann Arbor, MI 48104, USA.
Karen JamesonInstitute for Social Research, University of Michigan, Ann Arbor, MI 48104, USA.
Anders GrøntvedUnidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, Universidad Nacional Autónoma de México, Instituto Nacional de Medicina Genómica, Mexico City, Mexico.
Myriam FornageMRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
Stephen SidneyNational Institute for Health Research Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton General Hospital, Southampton SO16 6YD, UK.
Craig L HanisNational Institute for Health Research Biomedical Research Unit, University of Oxford, Oxford OX3 7LE, UK.
Heather M HighlandNational Institute for Health Research Biomedical Research Unit, University of Oxford, Oxford OX3 7LE, UK.
Hans-Ulrich HäringDepartment of Sport Science and Clinical Biomechanics, University of Southern Denmark, Odense DK-5230, Denmark, University of Texas Health Science Center at Houston Institute of Molecular Medicine and Division of Epidemiology Human Genetics and Environmental Sciences, School of Public Health, Houston, TX 77030, USA.
Martin HeniDepartment of Sport Science and Clinical Biomechanics, University of Southern Denmark, Odense DK-5230, Denmark, University of Texas Health Science Center at Houston Institute of Molecular Medicine and Division of Epidemiology Human Genetics and Environmental Sciences, School of Public Health, Houston, TX 77030, USA.
Jessica Lasky-SuDivision of Research, Kaiser Permanente of Northern California, Oakland, CA 94612, USA, The Human Genetics Center, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Scott T WeissDivision of Research, Kaiser Permanente of Northern California, Oakland, CA 94612, USA, The Human Genetics Center, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Glenn S GerhardInternal Medicine IV (Endocrinology, Diabetology, Angiology, Nephrology, and Clinical Chemistry), University Hospital of Tuebingen, Tübingen 72076, Germany.
Christopher StillGerman Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
Melkaey M MelkaThe Department of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Zdenka PausovaThe Department of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Tomáš PausCenter for Genomic Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Struan F A GrantDepartment of Biochemistry and Molecular Biology, Institute for Personalized Medicine, Department of Pathology and Laboratory Medicine, Pennsylvania State University, Hershey, PA 17033, USA, Geisinger Obesity Institute, Danville, PA 17822, USA.
Hakon HakonarsonDepartment of Biochemistry and Molecular Biology, Institute for Personalized Medicine, Department of Pathology and Laboratory Medicine, Pennsylvania State University, Hershey, PA 17033, USA, Geisinger Obesity Institute, Danville, PA 17822, USA.
R Arlen PriceThe Hospital for Sick Children, Department of Physiology, University of Toronto, Toronto, ON, Canada M5G 1X.
Kai WangMRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK, Rotman Research Institute, University of Toronto, Toronto, Canada M6A 2E1.
Andre ScheragCenter for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Johannes HebebrandDepartment of Pediatrics and.
Anke HinneyDepartment of Pediatrics and.
BioBank Japan, AGEN-BMI, GIANT Consortium
Paul W FranksDepartment of Medicine, University of Western Ontario, London, ON, Canada N6A 3K7, MRC Epidemiology Unit, University of Cambridge, Cambridge, UK, Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA.
Timothy M FraylingZilkha Neurogenetic Institute, Department of Psychiatry and Department of Preventive Medicine, University of Southern California, Los Angeles, CA 90089, USA.
Mark I McCarthyClinical Epidemiology, Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena 07740, Germany.
Joel N HirschhornDepartment of Child and Adolescent Psychiatry, University of Duisburg-Essen, Essen 45141, Germany, Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA, Genetics of Complex Traits, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter EX2 4TH, UK.
Ruth J LoosThe Research Institute of the McGill University Health Centre, McGill University, Montreal, QC, Canada H3H 2R9, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 9DU, UK.
Erik IngelssonDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Hertzel C GersteinDepartment of Clinical Epidemiology and Biostatistics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA, Divisions of Genetics and Endocrinology, Children's Hospital, Boston, MA 02115, USA.
Salim YusufDepartment of Clinical Epidemiology and Biostatistics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA, Divisions of Genetics and Endocrinology, Children's Hospital, Boston, MA 02115, USA.
Joseph BeyeneDepartment of Clinical Epidemiology and Biostatistics.
Sonia S AnandDepartment of Clinical Epidemiology and Biostatistics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA, Divisions of Genetics and Endocrinology, Children's Hospital, Boston, MA 02115, USA.
David MeyreDepartment of Clinical Epidemiology and Biostatistics, Divisions of Genetics and Endocrinology, Children's Hospital, Boston, MA 02115, USA, Department of Genetics, Harvard Medical School, Boston, MA 02115, USA, meyred@mcmaster.ca.
Cancer Research And Biostatistics · USUniversity of Cambridge · GBBoston Children's Hospital · USHarvard University · USMcGill University Health Centre · CAUniversity of Michigan · USBrigham and Women's Hospital · USKaiser Permanente · USNational Institute for Health Research · GBNovo Nordisk Foundation · DKPediatrics and Genetics · USPennsylvania State University · USThe University of Texas Health Science Center at Houston · USVanderbilt University · USChildren's Hospital of Philadelphia · USGerman Center for Diabetes Research · DEHospital for Sick Children · CAJena University Hospital · DELund University · SEMcMaster University · CA

Funding

Health and Retirement Study: Yrs 35-40U01AG009740 · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 1990 to 2025
$96.8M
THE PHARMACOGENETICS OF ASTHMA TREATMENTU01HL065899 · BRIGHAM AND WOMEN'S HOSPITAL · 2000 to 2005
$16.1M
SYSTEMS APPROACHES TO THE EPIDEMIOLOGY, GENETICS AND GENOMICS OF LUNG DISEASEST32HL007427 · HARVARD UNIVERSITY (MEDICAL SCHOOL) · 1985 to 2025
$2.4M
CORE--GENETICS, GENOMICS, AND GENETIC EPIDEMIOLOGYP30DK072488 · UNIVERSITY OF MARYLAND BALTIMORE · 2005 to 2005
$1.0M
Acid-Sensing Ion Channels in Cardiac IschemiaR01HL076419 · UNIVERSITY OF IOWA · 2005 to 2005
$369k
British Heart Foundation RG/08/014/24067Cancer Research UK 14136CIHRMedical Research Council G0401527Medical Research Council G1000143Medical Research Council MC_U106179471Medical Research Council MC_U147585827Medical Research Council MC_UP_A620_1014Medical Research Council MC_UP_A620_1015Medical Research Council MC_UU_12011/1Medical Research Council MC_UU_12011/2Medical Research Council MC_UU_12015/1Medical Research Council MR/L003120/1NHLBI NIH HHS P01 HL083069NHLBI NIH HHS R01 HL076419NHLBI NIH HHS T32 HL007427NHLBI NIH HHS T32 HL07427NHLBI NIH HHS U01 HL065899NHLBI NIH HHS U01 HL076419NHLBI NIH HHS U01 HL65899NIA NIH HHS U01 AG009740NIDDK NIH HHS DK072488NIDDK NIH HHS DK088231NIDDK NIH HHS P30 DK072488NIDDK NIH HHS R01 DK088231
6 · The paper itself

Abstract

Polymorphisms rs6232 and rs6234/rs6235 in PCSK1 have been associated with extreme obesity [e.g. body mass index (BMI) ≥ 40 kg/m(2)], but their contribution to common obesity (BMI ≥ 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 × 10(-6)) and rs6234/rs6235 (OR = 1.07, 95% CI 1.04-1.10, P = 3.00 × 10(-7)). Similarly, significant associations were found with continuous BMI for rs6232 (β = 0.03, 95% CI 0.00-0.07; P = 0.047) and rs6234/rs6235 (β = 0.02, 95% CI 0.00-0.03; P = 5.57 × 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.

Indexed as

Body Mass IndexGenetic Predisposition to DiseaseGenetic VariationAllelesHumansObesityOdds RatioPolymorphism, Single NucleotideProprotein Convertase 1PCSK1 protein, humanProprotein Convertase 1

Identifiers

PMID25784503
PMCPMC4498155
OpenAlexW2142133732

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.