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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Nutr.</journal-id>
<journal-title>Frontiers in Nutrition</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Nutr.</abbrev-journal-title>
<issn pub-type="epub">2296-861X</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fnut.2024.1265920</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Nutrition</subject>
<subj-group>
<subject>Original Research</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Diet and risk for hernia: a Mendelian randomization analysis</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name><surname>Yang</surname> <given-names>Yanjiang</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
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</contrib>
<contrib contrib-type="author" corresp="yes">
<name><surname>Han</surname> <given-names>Biao</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
<xref ref-type="corresp" rid="c001"><sup>&#x002A;</sup></xref>
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</contrib>
<contrib contrib-type="author" corresp="yes">
<name><surname>Yang</surname> <given-names>Wenwen</given-names></name>
<xref ref-type="aff" rid="aff4"><sup>4</sup></xref>
<xref ref-type="corresp" rid="c001"><sup>&#x002A;</sup></xref>
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<aff id="aff1"><sup>1</sup><institution>The People's Hospital of Qiandongnan Autonomous Prefecture</institution>, <addr-line>Kaili, Guizhou</addr-line>, <country>China</country></aff>
<aff id="aff2"><sup>2</sup><institution>Department of Thoracic Surgery, The First Hospital of Lanzhou University</institution>, <addr-line>Lanzhou, Gansu</addr-line>, <country>China</country></aff>
<aff id="aff3"><sup>3</sup><institution>Gansu Province International Cooperation Base for Research and Application of Key Technology of Thoracic Surgery, The First Hospital of Lanzhou University</institution>, <addr-line>Lanzhou, Gansu</addr-line>, <country>China</country></aff>
<aff id="aff4"><sup>4</sup><institution>The First Clinical Medical College, Lanzhou University</institution>, <addr-line>Lanzhou, Gansu</addr-line>, <country>China</country></aff>
<author-notes>
<fn fn-type="edited-by" id="fn0001"><p>Edited by: Annalisa Noce, University of Rome Tor Vergata, Italy</p></fn>
<fn fn-type="edited-by" id="fn0002"><p>Reviewed by: Juan Manuel Su&#x00E1;rez-Grau, Virgen del Roc&#x00ED;o University Hospital, Spain</p><p>Isabela Gobbo Ferreira, University of S&#x00E3;o Paulo, Ribeir&#x00E3;o Preto, Brazil</p><p>Heba Taher, Cairo University, Egypt</p></fn>
<corresp id="c001">&#x002A;Correspondence: Wenwen Yang, <email>1243012256@qq.com</email>; Biao Han, <email>hanbiao66@163.com</email></corresp>
</author-notes>
<pub-date pub-type="epub">
<day>18</day>
<month>06</month>
<year>2024</year>
</pub-date>
<pub-date pub-type="collection">
<year>2024</year>
</pub-date>
<volume>11</volume>
<elocation-id>1265920</elocation-id>
<history>
<date date-type="received">
<day>24</day>
<month>07</month>
<year>2023</year>
</date>
<date date-type="accepted">
<day>28</day>
<month>05</month>
<year>2024</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#x00A9; 2024 Yang, Han and Yang.</copyright-statement>
<copyright-year>2024</copyright-year>
<copyright-holder>Yang, Han and Yang</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p>
</license>
</permissions>
<abstract>
<sec id="sec1">
<title>Background</title>
<p>The relationship between dietary factors and hernias is currently unclear.</p>
</sec>
<sec id="sec2">
<title>Methods</title>
<p>The UK Biobank was used to extract dietary factors that were used as exposures, including intake of alcohol, non-oily fish, beef, fresh fruit, oily fish, salad/raw vegetables, dried fruit, coffee, cereal, salt, tea, water, cooked vegetables, cheese, Lamb/mutton, pork, poultry, processed meat, and bread. The FinnGen biobank was used to obtain GWAS data on hernias as outcomes. The main analysis of this study was performed using the weighted median, MR-Egger, and IVW methods. Cochran&#x2019;s Q test was utilized to assess heterogeneity. To find potential outliers, the MR-PRESSO method was used. Leave-one-out analysis was employed to assess the IVW method&#x2019;s robustness.</p>
</sec>
<sec id="sec3">
<title>Results</title>
<p>Alcoholic consumption per week (OR: 0.614; <italic>p</italic> =&#x2009;0.00614) reduced the risk of inguinal hernia. Alcohol intake frequency (OR: 1.309; <italic>p</italic> =&#x2009;0.0477) increased the risk of ventral hernia (mainly including incisional hernia and parastomal hernia). The intake of non-oily fish (OR: 2.945; <italic>p</italic> =&#x2009;0.0214) increased the risk of inguinal hernia. Salt added to food (OR: 1.841; <italic>p</italic> =&#x2009;0.00267) increased the risk of umbilical hernia. Cheese intake (OR: 0.434; <italic>p</italic> =&#x2009;0.000536) and dried fruit intake (OR: 0.322; <italic>p</italic> =&#x2009;0.00716) decreased the risk of ventral hernia, while cooked vegetable intake (OR: 4.475; <italic>p</italic> =&#x2009;0.0380) increased the risk of ventral hernia. No causal relationships were found with hernias from other dietary factors.</p>
</sec>
<sec id="sec4">
<title>Conclusion</title>
<p>Inguinal, umbilical, and ventral hernias are all related to dietary factors.</p>
</sec>
</abstract>
<kwd-group>
<kwd>Mendelian randomization</kwd>
<kwd>incisional hernia</kwd>
<kwd>dietary intake</kwd>
<kwd>umbilical hernia</kwd>
<kwd>inguinal hernia</kwd>
</kwd-group>
<counts>
<fig-count count="1"/>
<table-count count="1"/>
<equation-count count="0"/>
<ref-count count="33"/>
<page-count count="6"/>
<word-count count="3940"/>
</counts>
<custom-meta-wrap>
<custom-meta>
<meta-name>section-at-acceptance</meta-name>
<meta-value>Nutritional Epidemiology</meta-value>
</custom-meta>
</custom-meta-wrap>
</article-meta>
</front>
<body>
<sec sec-type="intro" id="sec5">
<label>1</label>
<title>Introduction</title>
<p>Inguinal hernia, umbilical hernia, and ventral hernia (including incisional hernia and parastomal hernia) are the three types of hernias, according to the 10th revision of the International Classification of Diseases. Inguinal hernias are the most common hernias, and umbilical hernias are also frequent hernias (<xref ref-type="bibr" rid="ref1">1</xref>). Incisional hernias occur after laparotomies at a rate of 5&#x2013;20% and more than 30% in high-risk individuals (<xref ref-type="bibr" rid="ref2">2</xref>). There have been many studies investigating risk factors for hernias (<xref ref-type="bibr" rid="ref3 ref4 ref5 ref6 ref7 ref8 ref9">3&#x2013;9</xref>), but few studies have analyzed the effects of dietary factors on hernias (<xref ref-type="bibr" rid="ref10">10</xref>). Dietary factors are important factors affecting health and disease (<xref ref-type="bibr" rid="ref11 ref12 ref13 ref14">11&#x2013;14</xref>). Therefore, this study used the methods of Mendelian randomization (MR) to analyze the effect of dietary factors on hernias.</p>
</sec>
<sec sec-type="methods" id="sec6">
<label>2</label>
<title>Methods</title>
<p>MR identifies the causal relationship between exposures and outcomes by employing genetic variations as instrumental variables (IVs). Three fundamental assumptions must be met for MR to function (<xref ref-type="bibr" rid="ref15">15</xref>). First, there was no connection between the IVs and any probable confounding factors. Second, there must be robust correlations between the IVs and exposure variables. Third, there are no direct connections between the IVs and outcomes. As a result of using deidentified and freely accessible data from the IEU Open GWAS project, this study was exempt from institutional review board approval.</p>
<sec id="sec7">
<label>2.1</label>
<title>The selection of IVs and the sources of data</title>
<p>Intake of beef, alcohol, non-oily fish, salad/raw vegetables, water, coffee, fresh fruit, oily fish, dried fruit, cereal, tea, salt, cooked vegetables, cheese, poultry, pork, lamb/mutton, bread, and processed meat were the dietary factors used as exposures in this study. The European-descent participants of dietary factors previously mentioned ranged from 335,394 to 462,630 individuals. The MRC Integrative Epidemiology Unit (IEU) at the University of Bristol funded the IEU open GWAS project, which either directly or indirectly extracted the GWAS data mentioned above from the UK Biobank. The GWAS data of Hernias (including umbilical, ventral, and inguinal hernias) were extracted from the FinnGen biobank. More information on the outcome and exposure datasets is provided in <xref ref-type="supplementary-material" rid="SM1">Supplementary Table S1</xref> and <xref ref-type="table" rid="tab1">Table 1</xref>. The IVs that were employed in the study were determined under the following criteria. First, we will immediately delete palindromic and missing SNPs. Second, linkage disequilibrium was at a level of r2&#x2009;&#x003C;&#x2009;0.001, the threshold of genome-wide significance <italic>p</italic> &#x003C;&#x2009;5&#x2009;&#x00D7;&#x2009;10<sup>&#x2212;8</sup>, and the clumping window at 10,000&#x2009;kb. Third, the F statistics of the IVs must be higher than 10.</p>
<table-wrap position="float" id="tab1">
<label>Table 1</label>
<caption>
<p>Information on exposure and outcome datasets.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top">IEU GWAS id</th>
<th align="left" valign="top">Exposure or outcome</th>
<th align="left" valign="top">Participants included in analysis</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="middle">ieu-b-73</td>
<td align="left" valign="middle">Alcoholic drinks per week</td>
<td align="left" valign="middle">335,394 European-descent individuals</td>
</tr>
<tr>
<td align="left" valign="middle">ukb-b-5779</td>
<td align="left" valign="middle">Alcohol intake frequency</td>
<td align="left" valign="middle">462,346 European-descent individuals</td>
</tr>
<tr>
<td align="left" valign="middle">ukb-b-6324</td>
<td align="left" valign="middle">Processed meat intake</td>
<td align="left" valign="middle">461,981 European-descent individuals</td>
</tr>
<tr>
<td align="left" valign="middle">ukb-b-8006</td>
<td align="left" valign="middle">Poultry intake</td>
<td align="left" valign="middle">461,900 European-descent individuals</td>
</tr>
<tr>
<td align="left" valign="middle">ukb-b-2862</td>
<td align="left" valign="middle">Beef intake</td>
<td align="left" valign="middle">461,053 European-descent individuals</td>
</tr>
<tr>
<td align="left" valign="middle">ukb-b-17627</td>
<td align="left" valign="middle">Non-oily fish intake</td>
<td align="left" valign="middle">460,880 European-descent individuals</td>
</tr>
<tr>
<td align="left" valign="middle">ukb-b-2209</td>
<td align="left" valign="middle">Oily fish intake</td>
<td align="left" valign="middle">460,443 European-descent individuals</td>
</tr>
<tr>
<td align="left" valign="middle">ukb-b-5640</td>
<td align="left" valign="middle">Pork intake</td>
<td align="left" valign="middle">460,162 European-descent individuals</td>
</tr>
<tr>
<td align="left" valign="middle">ukb-b-14179</td>
<td align="left" valign="middle">Lamb/mutton intake</td>
<td align="left" valign="middle">460,006 European-descent individuals</td>
</tr>
<tr>
<td align="left" valign="middle">ukb-b-11348</td>
<td align="left" valign="middle">Bread intake</td>
<td align="left" valign="middle">452,236 European-descent individuals</td>
</tr>
<tr>
<td align="left" valign="middle">ukb-b-1489</td>
<td align="left" valign="middle">Cheese intake</td>
<td align="left" valign="middle">451,486 European-descent individuals</td>
</tr>
<tr>
<td align="left" valign="middle">ukb-b-8089</td>
<td align="left" valign="middle">Cooked vegetable intake</td>
<td align="left" valign="middle">448,651 European-descent individuals</td>
</tr>
<tr>
<td align="left" valign="middle">ukb-b-6066</td>
<td align="left" valign="middle">Tea intake</td>
<td align="left" valign="middle">447,485 European-descent individuals</td>
</tr>
<tr>
<td align="left" valign="middle">ukb-b-3881</td>
<td align="left" valign="middle">Fresh fruit intake</td>
<td align="left" valign="middle">446,462 European-descent individuals</td>
</tr>
<tr>
<td align="left" valign="middle">ukb-b-15926</td>
<td align="left" valign="middle">Cereal intake</td>
<td align="left" valign="middle">441,640 European-descent individuals</td>
</tr>
<tr>
<td align="left" valign="middle">ukb-b-1996</td>
<td align="left" valign="middle">Salad / raw vegetable intake</td>
<td align="left" valign="middle">435,435 European-descent individuals</td>
</tr>
<tr>
<td align="left" valign="middle">ukb-b-5237</td>
<td align="left" valign="middle">Coffee intake</td>
<td align="left" valign="middle">428,860 European-descent individuals</td>
</tr>
<tr>
<td align="left" valign="middle">ukb-b-16576</td>
<td align="left" valign="middle">Dried fruit intake</td>
<td align="left" valign="middle">421,764 European-descent individuals</td>
</tr>
<tr>
<td align="left" valign="middle">ukb-b-8121</td>
<td align="left" valign="middle">Salt added to food</td>
<td align="left" valign="middle">462,630 European-descent individuals</td>
</tr>
<tr>
<td align="left" valign="middle">ukb-b-14898</td>
<td align="left" valign="middle">Water intake</td>
<td align="left" valign="middle">427,588 European-descent individuals</td>
</tr>
<tr>
<td align="left" valign="middle">finn-b-K11_UMBHER</td>
<td align="left" valign="middle">Umbilical hernia</td>
<td align="left" valign="middle">4,224 European-descent cases and 190,557 European-descent controls</td>
</tr>
<tr>
<td align="left" valign="middle">finn-b-K11_VENTHER</td>
<td align="left" valign="middle">Ventral hernia</td>
<td align="left" valign="middle">3,737 European-descent cases and 190,557 European-descent controls</td>
</tr>
<tr>
<td align="left" valign="middle">finn-b-K11_HERING</td>
<td align="left" valign="middle">Inguinal hernia</td>
<td align="left" valign="middle">17,096 European-descent cases and 190,557 European-descent controls</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>The information of the exposure and outcome datasets. More information about exposures and outcomes is available at the IEU OpenGWAS project (<ext-link xlink:href="https://gwas.mrcieu.ac.uk/" ext-link-type="uri">https://gwas.mrcieu.ac.uk/</ext-link>). IEU, Integrative Epidemiology Unit; GWAS, Genome-Wide Association Studies.</p>
</table-wrap-foot>
</table-wrap>
</sec>
<sec id="sec8">
<label>2.2</label>
<title>Statistical analysis</title>
<p>This study employed the inverse-variance weighted (IVW) method as the primary method for identifying causality. The IVW method, which requires that all SNPs remain valid or horizontal pleiotropy is balanced, offers the strongest power to identify causality (<xref ref-type="bibr" rid="ref16">16</xref>). The weighted median method and the MR-Egger method were utilized as supplements to the IVW method, which served as the major method to assess causality in our study. If their results are consistent with the IVW method, the reliability of the IVW method will be greatly improved. Leave-one-out analysis was applied to evaluate the IVW method&#x2019;s robustness. By employing the MR-Egger method, which allows for the existence of nonzero intercepts, the horizontal pleiotropy can be identified. To identify potential outliers, the MR-PRESSO method was used. Cochran&#x2019;s Q test was utilized to assess heterogeneity. The R program (version 4.2.0) and TwoSampleMR package (<xref ref-type="bibr" rid="ref17">17</xref>) were employed to perform all analyses.</p>
</sec>
</sec>
<sec sec-type="results" id="sec9">
<label>3</label>
<title>Results</title>
<p>As shown in <xref ref-type="supplementary-material" rid="SM1">Supplementary Table S2</xref>, horizontal pleiotropy was detected in the analyses of the effects of fresh fruit intake on umbilical hernia and salt added to food on inguinal hernia (<italic>p</italic> &#x003C;&#x2009;0.05). The presence of horizontal pleiotropy indicated that these analyses violated the assumptions of MR and that there were direct associations between IVs and outcomes (<xref ref-type="bibr" rid="ref18">18</xref>, <xref ref-type="bibr" rid="ref19">19</xref>). We will therefore treat them as invalid analyses. Utilizing the MR-PRESSO method, outliers were found in some analyses, but after removing the outliers and repeating the analyses, the results remained largely unchanged. The F statistics of IVs are all larger than 10, indicating that IVs and exposures have strong associations. The results of the MR-PRESSO method and F statistics are shown in the corresponding sections of <xref ref-type="supplementary-material" rid="SM1">Supplementary Table S2</xref>.</p>
<sec id="sec10">
<label>3.1</label>
<title>Dietary factors and inguinal hernia</title>
<p>Alcoholic drinks per week was observed to reduce the risk of inguinal hernia only in the IVW method (OR: 0.614; <italic>p</italic> =&#x2009;0.00614). The intake of non-oily fish was observed to increase the risk of inguinal hernia in the IVW method (OR: 2.945; <italic>p</italic> =&#x2009;0.0214) and the weighted median method (OR: 4.007; <italic>p</italic> =&#x2009;0.0128). Lamb/mutton intake was observed to decrease the risk of inguinal hernia only in the MR-Egger method (OR: 0.0735; <italic>p</italic> =&#x2009;0.0420). The MR-Egger method only complements the IVW method, so there is no causal relationship between lamb/mutton intake and inguinal hernia. <xref ref-type="fig" rid="fig1">Figure 1</xref> shows the results of the leave-one-out analysis of positive dietary factors. Salt added to food is considered as an invalid analysis due to the detection of horizontal pleiotropy. Alcohol intake frequency and the intake of processed meat, poultry, beef, oily fish, pork, bread, cheese, cooked vegetable, tea, fresh fruit, cereal, salad/raw vegetable, coffee, dried fruit, and water were not associated with inguinal hernia in all of the three analysis methods (<italic>p</italic> &#x003E;&#x2009;0.05). More analysis results are provided in <xref ref-type="supplementary-material" rid="SM1">Supplementary Table S2</xref>.</p>
<fig position="float" id="fig1">
<label>Figure 1</label>
<caption>
<p>The results of leave-one-out analyses for <bold>(A)</bold> salt added to food on umbilical hernia <bold>(B)</bold> alcohol intake frequency on ventral hernia <bold>(C)</bold> cheese intake on ventral hernia <bold>(D)</bold> dried fruit intake on ventral hernia <bold>(E)</bold> cooked vegetable intake on ventral hernia <bold>(F)</bold> non-oily fish intake on inguinal hernia <bold>(G)</bold> alcoholic drinks per week on inguinal hernia.</p>
</caption>
<graphic xlink:href="fnut-11-1265920-g001.tif"/>
</fig>
</sec>
<sec id="sec11">
<label>3.2</label>
<title>Dietary factors and umbilical hernia</title>
<p>Salt added to food (cooking salt is not included) was observed to increase the risk of umbilical hernia only in the IVW method (OR: 1.841; <italic>p</italic> =&#x2009;0.00267). <xref ref-type="fig" rid="fig1">Figure 1</xref> shows the results of the leave-one-out analysis of positive dietary factors. Fresh fruit intake is considered as an invalid analysis due to the detection of horizontal pleiotropy. Horizontal pleiotropy was not detected in dried fruit intake after removal of an outlier. Cooked vegetable intake was observed to increase the risk of umbilical hernia only in the weighted median method (OR: 5.038; <italic>p</italic> =&#x2009;0.0470). The weighted median method only complements the IVW method, so there is no causal relationship between cooked vegetable intake and umbilical hernia. The intake of alcohol, processed meat, non-oily fish, poultry, beef, oily fish, pork, lamb/mutton, bread, cheese, tea, cereal, salad/raw vegetable, coffee, dried fruit, and water were not associated with umbilical hernia in any of the three analysis methods (<italic>p</italic> &#x003E;&#x2009;0.05). More analysis results are provided in <xref ref-type="supplementary-material" rid="SM1">Supplementary Table S2</xref>.</p>
</sec>
<sec id="sec12">
<label>3.3</label>
<title>Dietary factors and ventral hernia</title>
<p>It should be noted that the ventral hernia used in this study is defined according to the 10th revision of the International Classification of Diseases, mainly including incisional hernia and parastomal hernia (<xref ref-type="bibr" rid="ref20">20</xref>).</p>
<p>Alcohol intake frequency was observed to increase the risk of ventral hernia only in the IVW method (OR: 1.309; <italic>p</italic> =&#x2009;0.0477). Cheese intake and dried fruit intake were observed to decrease the risk of ventral hernia in the IVW method (cheese intake OR: 0.434; <italic>p</italic> =&#x2009;0.000536; dried fruit intake OR: 0.322; <italic>p</italic> =&#x2009;0.00716) and the weighted median method (cheese intake OR: 0.391; <italic>p</italic> =&#x2009;0.00452; dried fruit intake OR: 0.239; <italic>p</italic> =&#x2009;0.0107). Cooked vegetable intake was observed to increase the risk of ventral hernia in the IVW method (OR: 4.475; <italic>p</italic> =&#x2009;0.0380) and the weighted median method (OR: 5.554; <italic>p</italic> =&#x2009;0.0427). <xref ref-type="fig" rid="fig1">Figure 1</xref> shows the results of the leave-one-out analysis of positive dietary factors. Non-oily fish intake was observed to increase the risk of ventral hernia only in the weighted median method (OR: 8.941; <italic>p</italic> =&#x2009;0.0224). The weighted median method only complements the IVW method, so there is no causal relationship between cooked vegetable intake and umbilical hernia. Alcoholic drinks per week, salt added to food, and the intake of processed meat, poultry, beef, oily fish, pork, lamb/mutton, bread, tea, cereal, salad/raw vegetable, coffee, fresh fruit, and water were not associated with ventral hernia in the three analysis methods (<italic>p</italic> &#x003E;&#x2009;0.05). More analysis results are provided in <xref ref-type="supplementary-material" rid="SM1">Supplementary Table S2</xref>.</p>
</sec>
</sec>
<sec sec-type="discussion" id="sec13">
<label>4</label>
<title>Discussion</title>
<p>The associations between nutritional factors and the risk of hernias have not been extensively studied (<xref ref-type="bibr" rid="ref10">10</xref>), regardless of the fact that diet is an important influencing factor of health (<xref ref-type="bibr" rid="ref21 ref22 ref23">21&#x2013;23</xref>). We only found one study from Turkey that focused on the relationship between dietary factors and hernias, and their study found that dietary factors such as cheese, red meat, chicken, nuts, and bread were associated with inguinal hernia (<xref ref-type="bibr" rid="ref10">10</xref>). Their study included only 115 people with groin and only used 3-day food consumption records; Therefore, we believe that their study has some limitations. Dietary factors are difficult to measure. The UK Biobank used the frequency to measure dietary factors, more information is provided in <xref ref-type="supplementary-material" rid="SM1">Supplementary Table S1</xref>. As changing eating habits is difficult, it is highly difficult to use randomized controlled trials to evaluate the effect of dietary factors on hernias. Observational epidemiology is often used to analyze the influence of research factors on study subjects. However, the presence of confounders (<xref ref-type="bibr" rid="ref24 ref25 ref26">24&#x2013;26</xref>), reverse causality (<xref ref-type="bibr" rid="ref27">27</xref>, <xref ref-type="bibr" rid="ref28">28</xref>), and other factors might bias the causal effects that observational epidemiology observed. The introduction of instrumental variables can effectively solve these shortcomings (<xref ref-type="bibr" rid="ref29">29</xref>, <xref ref-type="bibr" rid="ref30">30</xref>). MR, an analysis that uses genetic variation as IVs, is being utilized increasingly frequently. MR sits between observational epidemiology and interventional epidemiology in the hierarchy of evidence (<xref ref-type="bibr" rid="ref31">31</xref>). In this study, we used MR analysis methods to analyze the effects of 20 dietary factors on three common hernias. The results of this study suggest that alcohol intake has different effects on different hernias. Alcoholic drinks per week reduce the risk of inguinal hernia, alcohol intake frequency increases the risk of abdominal hernia, and alcohol intake does not have any effect on umbilical hernia. In some studies, there was no association between alcohol intake and developing inguinal hernia (<xref ref-type="bibr" rid="ref32">32</xref>, <xref ref-type="bibr" rid="ref33">33</xref>). However, it was found in a different study that individuals with inguinal hernias consumed more alcohol (<xref ref-type="bibr" rid="ref10">10</xref>). However, less than 1,000 cases of inguinal hernias were included in their analysis, which limited the credibility of their study. Our study included hundreds of thousands of individuals from the UK Biobank and the Finngen Biobank, therefore our study provided new evidence to clarify the relationship between alcohol intake and inguinal hernia. It is worth noting that the causal relationship between drinking frequency and ventral hernia may be influenced by a single SNP, as shown in <xref ref-type="fig" rid="fig1">Figure 1B</xref>. In addition, we found that non-oily fish intake increased the risk of inguinal hernia, salt added to food increased the risk of umbilical hernia, cheese intake, and dried fruit intake reduced the risk of ventral hernia, and cooked vegetable intake increased the risk of ventral hernia. It is important to note that neither the causality of non-oily fish consumption on inguinal hernia nor the causality of cooked vegetable intake on ventral hernia are particularly stable; they are affected by a single SNP. More information is shown in <xref ref-type="fig" rid="fig1">Figures 1E</xref>,<xref ref-type="fig" rid="fig1">F</xref>. We must be particularly careful when interpreting these findings. First, the causal relationship observed by the MR analysis is the consequence of prolonged exposure to dietary factors. Therefore, short-term exposure may not have any clinical effect. Second, the Two-sample MR analysis only revealed the overall effects of exposures on outcomes, not the direct effects. Extremely complex pathways may link exposures and outcomes.</p>
<p>Unavoidably, this study has several restrictions. First, we were incapable of assessing whether there was a U-shaped correlation (for example, as dried fruit intake increases, the risk of ventral hernia rises first and then decreases) between dietary factors and hernias due to continuous data on dietary factors being employed in this study. Second, due to the lack of GWAS data for the two demographics of sex and age, we were unable to conduct stratified analyses. Third, the inability to further divide dietary intake categories prevents a more detailed analysis. Fourth, because our analysis primarily focuses on individuals from Europe, extending our findings to other populations is difficult.</p>
</sec>
<sec sec-type="conclusions" id="sec14">
<label>5</label>
<title>Conclusion</title>
<p>Alcoholic drinks per week will reduce the risk of inguinal hernia, while alcohol intake frequency will not affect the risk of inguinal hernia. Alcohol intake frequency will increase the risk of ventral hernia, while alcoholic drinks per week will not affect the risk of ventral hernia. Alcohol intake will not affect the risk of umbilical hernia. The intake of non-oily fish will increase the risk of inguinal hernia. Salt added to food will increase the risk of umbilical hernia. Cheese intake and dried fruit intake will decrease the risk of ventral hernia, while cooked vegetable intake will increase the risk of ventral hernia. No causal relationships were found with hernias from other dietary factors.</p>
</sec>
<sec sec-type="data-availability" id="sec15">
<title>Data availability statement</title>
<p>The original contributions presented in the study are included in the article/<xref ref-type="supplementary-material" rid="SM1">Supplementary materials</xref>, further inquiries can be directed to the corresponding author/s.</p>
</sec>
<sec sec-type="ethics-statement" id="sec16">
<title>Ethics statement</title>
<p>Ethical approval was not required for the study involving humans in accordance with the local legislation and institutional requirements. Written informed consent to participate in this study was not required from the participants or the participants&#x2019; legal guardians/next of kin in accordance with the national legislation and the institutional requirements.</p>
</sec>
<sec sec-type="author-contributions" id="sec17">
<title>Author contributions</title>
<p>YY: Data curation, Methodology, Formal analysis, Project administration, Validation, Funding acquisition, Resources, Visualization, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing. BH: Data curation, Methodology, Formal analysis, Project administration, Funding acquisition, Resources, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing. YW: Data curation, Methodology, Supervision, Conceptualization, Formal analysis, Project administration, Validation, Investigation, Funding acquisition, Resources, Visualization, Software, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing.</p>
</sec>
</body>
<back>
<sec sec-type="funding-information" id="sec18">
<title>Funding</title>
<p>The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.</p>
</sec>
<ack>
<p>Special thanks to the IEU open GWAS project developed by The MRC Integrative Epidemiology Unit (IEU) at the University of Bristol. Thank them for extracting relevant GWAS summary-level data from published articles, UK Biobank, and FinnGen Biobank.</p>
</ack>
<sec sec-type="COI-statement" id="sec19">
<title>Conflict of interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec sec-type="disclaimer" id="sec20">
<title>Publisher&#x2019;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
<sec sec-type="supplementary-material" id="sec21">
<title>Supplementary material</title>
<p>The Supplementary material for this article can be found online at: <ext-link xlink:href="https://www.frontiersin.org/articles/10.3389/fnut.2024.1265920/full#supplementary-material" ext-link-type="uri">https://www.frontiersin.org/articles/10.3389/fnut.2024.1265920/full#supplementary-material</ext-link></p>
<supplementary-material xlink:href="Table_1.docx" id="SM1" mimetype="application/vnd.openxmlformats-officedocument.wordprocessingml.document" xmlns:xlink="http://www.w3.org/1999/xlink"/>
<supplementary-material xlink:href="Table_2.DOCX" id="SM2" mimetype="application/vnd.openxmlformats-officedocument.wordprocessingml.document" xmlns:xlink="http://www.w3.org/1999/xlink"/>
</sec>
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