Detail
Článek
Článek online
FT
Medvik - BMČ
  • Je něco špatně v tomto záznamu ?

Search for multiple myeloma risk factors using Mendelian randomization

M. Went, AJ. Cornish, PJ. Law, B. Kinnersley, M. van Duin, N. Weinhold, A. Försti, M. Hansson, P. Sonneveld, H. Goldschmidt, GJ. Morgan, K. Hemminki, B. Nilsson, M. Kaiser, RS. Houlston

. 2020 ; 4 (10) : 2172-2179. [pub] 20200526

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc21020542

Grantová podpora
C1298/A8362 Cancer Research UK - United Kingdom

The etiology of multiple myeloma (MM) is poorly understood. Summary data from genome-wide association studies (GWASs) of multiple phenotypes can be exploited in a Mendelian randomization (MR) phenome-wide association study (PheWAS) to search for factors influencing MM risk. We performed an MR-PheWAS analyzing 249 phenotypes, proxied by 10 225 genetic variants, and summary genetic data from a GWAS of 7717 MM cases and 29 304 controls. Odds ratios (ORs) per 1 standard deviation increase in each phenotype were estimated under an inverse variance weighted random effects model. A Bonferroni-corrected threshold of P = 2 × 10-4 was considered significant, whereas P < .05 was considered suggestive of an association. Although no significant associations with MM risk were observed among the 249 phenotypes, 28 phenotypes showed evidence suggestive of association, including increased levels of serum vitamin B6 and blood carnitine (P = 1.1 × 10-3) with greater MM risk and ω-3 fatty acids (P = 5.4 × 10-4) with reduced MM risk. A suggestive association between increased telomere length and reduced MM risk was also noted; however, this association was primarily driven by the previously identified risk variant rs10936599 at 3q26 (TERC). Although not statistically significant, increased body mass index was associated with increased risk (OR, 1.10; 95% confidence interval, 0.99-1.22), supporting findings from a previous meta-analysis of prospective observational studies. Our study did not provide evidence supporting any modifiable factors examined as having a major influence on MM risk; however, it provides insight into factors for which the evidence has previously been mixed.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc21020542
003      
CZ-PrNML
005      
20210830102207.0
007      
ta
008      
210728s2020 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1182/bloodadvances.2020001502 $2 doi
035    __
$a (PubMed)32433745
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Went, Molly $u Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom
245    10
$a Search for multiple myeloma risk factors using Mendelian randomization / $c M. Went, AJ. Cornish, PJ. Law, B. Kinnersley, M. van Duin, N. Weinhold, A. Försti, M. Hansson, P. Sonneveld, H. Goldschmidt, GJ. Morgan, K. Hemminki, B. Nilsson, M. Kaiser, RS. Houlston
520    9_
$a The etiology of multiple myeloma (MM) is poorly understood. Summary data from genome-wide association studies (GWASs) of multiple phenotypes can be exploited in a Mendelian randomization (MR) phenome-wide association study (PheWAS) to search for factors influencing MM risk. We performed an MR-PheWAS analyzing 249 phenotypes, proxied by 10 225 genetic variants, and summary genetic data from a GWAS of 7717 MM cases and 29 304 controls. Odds ratios (ORs) per 1 standard deviation increase in each phenotype were estimated under an inverse variance weighted random effects model. A Bonferroni-corrected threshold of P = 2 × 10-4 was considered significant, whereas P < .05 was considered suggestive of an association. Although no significant associations with MM risk were observed among the 249 phenotypes, 28 phenotypes showed evidence suggestive of association, including increased levels of serum vitamin B6 and blood carnitine (P = 1.1 × 10-3) with greater MM risk and ω-3 fatty acids (P = 5.4 × 10-4) with reduced MM risk. A suggestive association between increased telomere length and reduced MM risk was also noted; however, this association was primarily driven by the previously identified risk variant rs10936599 at 3q26 (TERC). Although not statistically significant, increased body mass index was associated with increased risk (OR, 1.10; 95% confidence interval, 0.99-1.22), supporting findings from a previous meta-analysis of prospective observational studies. Our study did not provide evidence supporting any modifiable factors examined as having a major influence on MM risk; however, it provides insight into factors for which the evidence has previously been mixed.
650    12
$a celogenomová asociační studie $7 D055106
650    _2
$a lidé $7 D006801
650    _2
$a mendelovská randomizace $7 D057182
650    12
$a mnohočetný myelom $x epidemiologie $x genetika $7 D009101
650    _2
$a jednonukleotidový polymorfismus $7 D020641
650    _2
$a rizikové faktory $7 D012307
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Cornish, Alex J $u Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom
700    1_
$a Law, Philip J $u Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom
700    1_
$a Kinnersley, Ben $u Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom
700    1_
$a van Duin, Mark $u Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
700    1_
$a Weinhold, Niels $u Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany
700    1_
$a Försti, Asta $u Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany $u Hopp Children's Cancer Center, Heidelberg, Germany $u Division of Pediatric Neurooncology, DKFZ, DKTK, Heidelberg, Germany
700    1_
$a Hansson, Markus $u Hematology and Transfusion Medicine, Department of Laboratory Medicine, Biomedical Centre, Lund University, Lund, Sweden $u Hematology Clinic, Skåne University Hospital, Lund, Sweden
700    1_
$a Sonneveld, Pieter $u Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
700    1_
$a Goldschmidt, Hartmut $u Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany $u National Centre of Tumor Diseases, Heidelberg, Germany
700    1_
$a Morgan, Gareth J $u NYU Langone Health Care, New York, NY
700    1_
$a Hemminki, Kari $u Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany $u Division of Cancer Epidemiology, DKFZ, DKTK, Heidelberg, Germany $u Biomedical Center, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen, Czech Republic
700    1_
$a Nilsson, Björn $u Hematology and Transfusion Medicine, Department of Laboratory Medicine, Biomedical Centre, Lund University, Lund, Sweden $u Broad Institute, Cambridge, MA; and
700    1_
$a Kaiser, Martin $u Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom
700    1_
$a Houlston, Richard S $u Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom $u Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom
773    0_
$w MED00194912 $t Blood advances $x 2473-9537 $g Roč. 4, č. 10 (2020), s. 2172-2179
856    41
$u https://pubmed.ncbi.nlm.nih.gov/32433745 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20210728 $b ABA008
991    __
$a 20210830102207 $b ABA008
999    __
$a ok $b bmc $g 1691169 $s 1140988
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2020 $b 4 $c 10 $d 2172-2179 $e 20200526 $i 2473-9537 $m Blood advances $n Blood Adv $x MED00194912
GRA    __
$a C1298/A8362 $p Cancer Research UK $2 United Kingdom
LZP    __
$a Pubmed-20210728

Najít záznam

Citační ukazatele

Pouze přihlášení uživatelé

Možnosti archivace