Evidence map›Paper›PMID 24978468›Full record

ArticlePloS one2014

Systematic fine-mapping of association with BMI and type 2 diabetes at the FTO locus by integrating results from multiple ethnic groups.

Koichi Akiyama, Fumihiko Takeuchi, Masato Isono, Sureka Chakrawarthy, Quang Ngoc Nguyen, Wanqing Wen, Ken Yamamoto, Tomohiro Katsuya, Anuradhani Kasturiratne, Son Thai Pham and 8 more

Abstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Technologies, strategies, and cautions when deconvoluting genome-wide association signals: FTO in focus.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2023
    Review
  4. Article
  5. Article
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

18 authors.

Koichi AkiyamaDepartment of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
Fumihiko TakeuchiDepartment of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
Masato IsonoDepartment of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
Sureka ChakrawarthyDepartment of Public Health, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka.
Quang Ngoc NguyenBach Mai Hospital, Hanoi, Vietnam.
Wanqing WenDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
Ken YamamotoDivision of Genomics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Tomohiro KatsuyaDepartment of Clinical Gene Therapy, Osaka University Graduate School of Medicine, Suita, Japan; Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Suita, Japan.
Anuradhani KasturiratneDepartment of Public Health, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka.
Son Thai PhamBach Mai Hospital, Hanoi, Vietnam.
Wei ZhengDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
Yumi MatsushitaCenter for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan.
Miyako KishimotoCenter Hospital, National Center for Global Health and Medicine, Tokyo, Japan.
Loi Doan DoBach Mai Hospital, Hanoi, Vietnam.
Xiao-Ou ShuDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
Ananda R WickremasingheDepartment of Public Health, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka.
Hiroshi KajioCenter Hospital, National Center for Global Health and Medicine, Tokyo, Japan.
Norihiro KatoDepartment of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.

Funding

Shanghai Womens Health StudyUM1CA182910 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI ZHENG, WEI · 2014 to 2018
$5.9M
Shanghai Men's Health StudyUM1CA173640 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI SHU, XIAO-OU · 2013 to 2017
$4.9M
NCI NIH HHS UM1 CA173640NCI NIH HHS UM1 CA182910
6 · The paper itself

Abstract

BACKGROUND/

objectiveThe 16q12.2 locus in the first intron of FTO has been robustly associated with body mass index (BMI) and type 2 diabetes in genome-wide association studies (GWAS). To improve the resolution of fine-scale mapping at FTO, we performed a systematic approach consisting of two parts.

methodsThe first part is to partition the associated variants into linkage disequilibrium (LD) clusters, followed by conditional and haplotype analyses. The second part is to filter the list of potential causal variants through trans-ethnic comparison.

resultsWe first examined the LD relationship between FTO SNPs showing significant association with type 2 diabetes in Japanese GWAS and between those previously reported in European GWAS. We could partition all the assayed or imputed SNPs showing significant association in the target FTO region into 7 LD clusters. Assaying 9 selected SNPs in 4 Asian-descent populations--Japanese, Vietnamese, Sri Lankan and Chinese (n≤26,109 for BMI association and n≤24,079 for type 2 diabetes association), we identified a responsible haplotype tagged by a cluster of SNPs and successfully narrowed the list of potential causal variants to 25 SNPs, which are the smallest in number among the studies conducted to date for FTO.

conclusionsOur data support that the power to resolve the causal variants from those in strong LD increases consistently when three distant populations--Europeans, Asians and Africans--are included in the follow-up study. It has to be noted that this fine-mapping approach has the advantage of applicability to the existing GWAS data set in combination with direct genotyping of selected variants.

Indexed as

Body Mass IndexAdultAlpha-Ketoglutarate-Dependent Dioxygenase FTOAsian PeopleDiabetes Mellitus, Type 2FemaleHumansLinkage DisequilibriumMaleMiddle AgedPolymorphism, Single NucleotideProteinsAlpha-Ketoglutarate-Dependent Dioxygenase FTOFTO protein, humanProteins

Identifiers

PMID24978468
PMCPMC4076329

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Registered trials

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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 OpenQuestion graph.