Genome‐wide association study of circulating folate one‐carbon metabolites Article Swipe
Jun Wang
,
Isaac Asante
,
John A. Baron
,
Jane C. Figueiredo
,
Robert W. Haile
,
A. Joan Levine
,
Polly A. Newcomb
,
Allyson Templeton
,
Fredrick R. Schumacher
,
Stan G. Louie
,
Graham Casey
,
David V. Conti
·
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.1002/gepi.22249
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.1002/gepi.22249
Experimental, observational, and clinical trials support a critical role of folate one‐carbon metabolism (FOCM) in colorectal cancer (CRC) development. In this report, we focus on understanding the relationship between common genetic variants and metabolites of FOCM. We conducted a genome‐wide association study of FOCM biomarkers among 1,788 unaffected (without CRC) individuals of European ancestry from the Colon Cancer Family Registry. Twelve metabolites, including 5‐methyltetrahydrofolate, vitamin B 2 (flavin mononucleotide and riboflavin), vitamin B 6 (4‐pyridoxic acid, pyridoxal, and pyridoxamine), total homocysteine, methionine, S ‐adenosylmethionine, S ‐adenosylhomocysteine, cystathionine, and creatinine were measured from plasma using liquid chromatography‐mass spectrometry (LC‐MS) or LC‐MS/MS. For each individual biomarker, we estimated genotype array‐specific associations followed by a fixed‐effect meta‐analysis. We identified the variant rs35976024 (at 2p11.2 and intronic of ATOH8 ) associated with total homocysteine ( p = 4.9 × 10 −8 ). We found a group of six highly correlated variants on chromosome 15q14 associated with cystathionine (all p < 5 × 10 −8 ), with the most significant variant rs28391580 ( p = 2.8 × 10 −8 ). Two variants (rs139435405 and rs149119426) on chromosome 14q13 showed significant ( p < 5 × 10 −8 ) associations with S‐adenosylhomocysteine. These three biomarkers with significant associations are closely involved in homocysteine metabolism. Furthermore, when assessing the principal components (PCs) derived from seven individual biomarkers, we identified the variant rs12665366 (at 6p25.3 and intronic of EXOC2 ) associated with the first PC ( p = 2.3 × 10 −8 ). Our data suggest that common genetic variants may play an important role in FOCM, particularly in homocysteine metabolism.
Related Topics
Concepts
Cystathionine beta synthase
Genetics
Homocysteine
Biology
Genotype
Quantitative trait locus
Genome-wide association study
Colorectal cancer
Methionine
Internal medicine
Biochemistry
Medicine
Gene
Single-nucleotide polymorphism
Cancer
Amino acid
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1002/gepi.22249
- OA Status
- green
- Cited By
- 4
- References
- 74
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2972884066
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W2972884066Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1002/gepi.22249Digital Object Identifier
- Title
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Genome‐wide association study of circulating folate one‐carbon metabolitesWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2019Year of publication
- Publication date
-
2019-09-10Full publication date if available
- Authors
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Jun Wang, Isaac Asante, John A. Baron, Jane C. Figueiredo, Robert W. Haile, A. Joan Levine, Polly A. Newcomb, Allyson Templeton, Fredrick R. Schumacher, Stan G. Louie, Graham Casey, David V. ContiList of authors in order
- Landing page
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https://doi.org/10.1002/gepi.22249Publisher landing page
- Open access
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YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
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https://www.ncbi.nlm.nih.gov/pmc/articles/6829035Direct OA link when available
- Concepts
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Cystathionine beta synthase, Genetics, Homocysteine, Biology, Genotype, Quantitative trait locus, Genome-wide association study, Colorectal cancer, Methionine, Internal medicine, Biochemistry, Medicine, Gene, Single-nucleotide polymorphism, Cancer, Amino acidTop concepts (fields/topics) attached by OpenAlex
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4Total citation count in OpenAlex
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2024: 1, 2022: 1, 2021: 1, 2020: 1Per-year citation counts (last 5 years)
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74Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.from | 55, 92, 217 |
| abstract_inverted_index.most | 164 |
| abstract_inverted_index.play | 254 |
| abstract_inverted_index.role | 9, 257 |
| abstract_inverted_index.that | 249 |
| abstract_inverted_index.this | 21 |
| abstract_inverted_index.were | 90 |
| abstract_inverted_index.when | 210 |
| abstract_inverted_index.with | 128, 152, 162, 195, 200, 234 |
| abstract_inverted_index.−8 | 137, 160, 174, 192, 244 |
| abstract_inverted_index.(CRC) | 18 |
| abstract_inverted_index.(PCs) | 215 |
| abstract_inverted_index.1,788 | 47 |
| abstract_inverted_index.14q13 | 183 |
| abstract_inverted_index.15q14 | 150 |
| abstract_inverted_index.ATOH8 | 125 |
| abstract_inverted_index.Colon | 57 |
| abstract_inverted_index.EXOC2 | 231 |
| abstract_inverted_index.FOCM, | 259 |
| abstract_inverted_index.FOCM. | 36 |
| abstract_inverted_index.These | 197 |
| abstract_inverted_index.acid, | 76 |
| abstract_inverted_index.among | 46 |
| abstract_inverted_index.first | 236 |
| abstract_inverted_index.focus | 24 |
| abstract_inverted_index.found | 140 |
| abstract_inverted_index.group | 142 |
| abstract_inverted_index.seven | 218 |
| abstract_inverted_index.study | 42 |
| abstract_inverted_index.three | 198 |
| abstract_inverted_index.total | 80, 129 |
| abstract_inverted_index.using | 94 |
| abstract_inverted_index.(FOCM) | 14 |
| abstract_inverted_index.2p11.2 | 121 |
| abstract_inverted_index.6p25.3 | 227 |
| abstract_inverted_index.Cancer | 58 |
| abstract_inverted_index.Family | 59 |
| abstract_inverted_index.Twelve | 61 |
| abstract_inverted_index.cancer | 17 |
| abstract_inverted_index.common | 30, 250 |
| abstract_inverted_index.folate | 11 |
| abstract_inverted_index.highly | 145 |
| abstract_inverted_index.liquid | 95 |
| abstract_inverted_index.plasma | 93 |
| abstract_inverted_index.showed | 184 |
| abstract_inverted_index.trials | 5 |
| abstract_inverted_index.(flavin | 68 |
| abstract_inverted_index.between | 29 |
| abstract_inverted_index.closely | 204 |
| abstract_inverted_index.derived | 216 |
| abstract_inverted_index.genetic | 31, 251 |
| abstract_inverted_index.report, | 22 |
| abstract_inverted_index.suggest | 248 |
| abstract_inverted_index.support | 6 |
| abstract_inverted_index.variant | 118, 166, 224 |
| abstract_inverted_index.vitamin | 65, 72 |
| abstract_inverted_index.(without | 49 |
| abstract_inverted_index.Abstract | 0 |
| abstract_inverted_index.European | 53 |
| abstract_inverted_index.ancestry | 54 |
| abstract_inverted_index.clinical | 4 |
| abstract_inverted_index.critical | 8 |
| abstract_inverted_index.followed | 110 |
| abstract_inverted_index.genotype | 107 |
| abstract_inverted_index.intronic | 123, 229 |
| abstract_inverted_index.involved | 205 |
| abstract_inverted_index.measured | 91 |
| abstract_inverted_index.variants | 32, 147, 177, 252 |
| abstract_inverted_index.(LC‐MS) | 98 |
| abstract_inverted_index.Registry. | 60 |
| abstract_inverted_index.assessing | 211 |
| abstract_inverted_index.conducted | 38 |
| abstract_inverted_index.estimated | 106 |
| abstract_inverted_index.important | 256 |
| abstract_inverted_index.including | 63 |
| abstract_inverted_index.principal | 213 |
| abstract_inverted_index.associated | 127, 151, 233 |
| abstract_inverted_index.biomarker, | 104 |
| abstract_inverted_index.biomarkers | 45, 199 |
| abstract_inverted_index.chromosome | 149, 182 |
| abstract_inverted_index.colorectal | 16 |
| abstract_inverted_index.components | 214 |
| abstract_inverted_index.correlated | 146 |
| abstract_inverted_index.creatinine | 89 |
| abstract_inverted_index.identified | 116, 222 |
| abstract_inverted_index.individual | 103, 219 |
| abstract_inverted_index.metabolism | 13 |
| abstract_inverted_index.pyridoxal, | 77 |
| abstract_inverted_index.rs12665366 | 225 |
| abstract_inverted_index.rs28391580 | 167 |
| abstract_inverted_index.rs35976024 | 119 |
| abstract_inverted_index.unaffected | 48 |
| abstract_inverted_index.LC‐MS/MS. | 100 |
| abstract_inverted_index.association | 41 |
| abstract_inverted_index.biomarkers, | 220 |
| abstract_inverted_index.individuals | 51 |
| abstract_inverted_index.metabolism. | 208, 263 |
| abstract_inverted_index.metabolites | 34 |
| abstract_inverted_index.methionine, | 82 |
| abstract_inverted_index.significant | 165, 185, 201 |
| abstract_inverted_index.(rs139435405 | 178 |
| abstract_inverted_index.Furthermore, | 209 |
| abstract_inverted_index.associations | 109, 194, 202 |
| abstract_inverted_index.development. | 19 |
| abstract_inverted_index.homocysteine | 130, 207, 262 |
| abstract_inverted_index.metabolites, | 62 |
| abstract_inverted_index.one‐carbon | 12 |
| abstract_inverted_index.particularly | 260 |
| abstract_inverted_index.relationship | 28 |
| abstract_inverted_index.riboflavin), | 71 |
| abstract_inverted_index.rs149119426) | 180 |
| abstract_inverted_index.spectrometry | 97 |
| abstract_inverted_index.Experimental, | 1 |
| abstract_inverted_index.cystathionine | 153 |
| abstract_inverted_index.genome‐wide | 40 |
| abstract_inverted_index.homocysteine, | 81 |
| abstract_inverted_index.understanding | 26 |
| abstract_inverted_index.(4‐pyridoxic | 75 |
| abstract_inverted_index.cystathionine, | 87 |
| abstract_inverted_index.fixed‐effect | 113 |
| abstract_inverted_index.mononucleotide | 69 |
| abstract_inverted_index.observational, | 2 |
| abstract_inverted_index.pyridoxamine), | 79 |
| abstract_inverted_index.array‐specific | 108 |
| abstract_inverted_index.meta‐analysis. | 114 |
| abstract_inverted_index.chromatography‐mass | 96 |
| abstract_inverted_index.‐adenosylmethionine, | 84 |
| abstract_inverted_index.‐adenosylhomocysteine, | 86 |
| abstract_inverted_index.S‐adenosylhomocysteine. | 196 |
| abstract_inverted_index.5‐methyltetrahydrofolate, | 64 |
| cited_by_percentile_year.max | 94 |
| cited_by_percentile_year.min | 89 |
| corresponding_author_ids | https://openalex.org/A5101926916 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 12 |
| corresponding_institution_ids | https://openalex.org/I1174212 |
| citation_normalized_percentile.value | 0.69244521 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |