OSCR

Plasma metabolomic signatures of migraine in 479,760 adults.

Code ↔ Paper

9 matches between paragraphs of the paper and lines of its authors' code, computed by the harvester (lexical-v1). Click a colored paragraph or line to see its counterpart.

The 9 matches
  1. [1] § STAR★Methods › Quantification and statistical analysis › Downstream integrative analyses ↔ 4.SEM.R, lines 1–57 · score 0.92 · formal causal mediation, LASSO prioritized metabolites, latent metabolite factor, affective traits, exploratory statistical, statistical interrelationships
  2. [2] § Results › Integration with genetic risk and cross-trait associations ↔ 4.SEM.R, lines 1–57 · score 0.90 · exploratory statistical interrelationshi, causal mediation, latent metabolite factor, affective trait, LASSO prioritized, exploratory structural
  3. [3] § STAR★Methods › Method details › Covariates ↔ 2.Trajectories+clusters.R, lines 1–63 · score 0.68 · alcohol consumption, smoking status, sleep duration, diabetes, age, Covariates
  4. [4] § STAR★Methods › Method details › Covariates ↔ 1.Cox+linear.R, lines 1–42 · score 0.68 · alcohol consumption, smoking status, sleep duration, diabetes, age, Covariates
  5. [5] § Results › Study population and metabolite profiling ↔ 1.Cox+linear.R, lines 1–42 · score 0.65 · diabetes status, smoking status, sleep duration, plasma metabolites, BMI, migraine
  6. [6] § STAR★Methods › Quantification and statistical analysis › Association analyses of plasma metabolites with migraine ↔ 1.Cox+linear.R, lines 385–456 · score 0.65 · Hazard ratios, prevalent migraine, linear, stratified, Cox, age
  7. [7] § STAR★Methods › Method details › Plasma metabolomics profiling ↔ Protocol_demo/run_synthetic_example.R, lines 586–716 · score 0.58 · quality control, log, preprocessing, medians, absolute, scores
  8. [8] § STAR★Methods › Method details › Assessment of migraine status ↔ Protocol_demo/generate_synthetic_data.R, lines 71–184 · score 0.56 · event date, diagnosis date, UKB, status, baseline, incident
  9. [9] § Results › Metabolite feature prioritization ↔ 4.SEM.R, lines 280–336 · score 0.52 · latent metabolite factor, sleep duration, SEM, insomnia, anxiety, depression

Paper

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The authors' code

R · 336 lines · 8.7 KB · no license · 3 matches

  1. #!/usr/bin/env Rscript
  2. # ============================================================
  3. # SEM analysis: latent metabolite factor and incident migraine
  4. # ============================================================
  5. # Purpose:
  6. # Fit exploratory structural equation models linking selected
  7. # sleep/affective traits, a latent metabolite factor, and
  8. # incident migraine.
  9. #
  10. # Required input object:
  11. # dat_base: individual-level analysis dataset containing:
  12. # - incident_migraine
  13. # - prevalent_depression, prevalent_anxiety, insomnia, sleep duration
  14. # - 12 LASSO-prioritized metabolite variables
  15. # - covariates listed below
  16. #
  17. # Optional input object:
  18. # meta_reverse_map: named vector mapping Met IDs to metabolite names
  19. #
  20. # Note:
  21. # These SEMs are exploratory statistical interrelationship models.
  22. # They should not be interpreted as formal causal mediation analyses.
  23. # ============================================================
  24. suppressPackageStartupMessages({
  25. library(dplyr)
  26. library(data.table)
  27. library(lavaan)
  28. library(fastDummies)
  29. library(stringr)
  30. library(purrr)
  31. })
  32. # -----------------------------
  33. # User parameters
  34. # -----------------------------
  35. result_dir <- "results"
  36. dir.create(result_dir, showWarnings = FALSE, recursive = TRUE)
  37. lasso_meta_cols <- c(
  38. "Met38", "Met57", "Met60", "Met82",
  39. "Met88", "Met111", "Met120", "Met125",
  40. "Met146", "Met201", "Met245", "Met246"
  41. )
  42. exposures <- c(
  43. dep_status = "Depression",
  44. anx_status = "Anxiety",
  45. insom_status = "Insomnia",
  46. sleep_hours = "Sleep duration"
  47. )
  48. base_covars <- c(
  49. "age", "sex", "ethn", "Qualification", "bmi", "Socioeconomic",
  50. "Smoking_status", "Alcohol_consumption"
  51. )
  52. # -----------------------------
  53. # Helper functions
  54. # -----------------------------
  55. check_required_vars <- function(dat, vars) {
  56. missing_vars <- setdiff(vars, names(dat))
  57. if (length(missing_vars) > 0) {
  58. stop("Missing required variables: ", paste(missing_vars, collapse = ", "))
  59. }
  60. }
  61. make_metabolite_map <- function(meta_cols) {
  62. if (exists("meta_reverse_map")) {
  63. data.frame(
  64. Metabolite_ID = names(meta_reverse_map),
  65. Metabolite_name = unname(meta_reverse_map),
  66. stringsAsFactors = FALSE
  67. )
  68. } else {
  69. data.frame(
  70. Metabolite_ID = meta_cols,
  71. Metabolite_name = meta_cols,
  72. stringsAsFactors = FALSE
  73. )
  74. }
  75. }
  76. prepare_sem_data <- function(dat, meta_cols) {
  77. dat <- dat %>%
  78. mutate(
  79. migraine_incident = as.integer(incident_migraine == 1),
  80. dep_status = as.integer(prevalent_depression == 1),
  81. anx_status = as.integer(prevalent_anxiety == 1),
  82. insom_status = as.numeric(insomnia),
  83. sleep_hours = as.numeric(`sleep duration`),
  84. age = as.numeric(age),
  85. bmi = as.numeric(bmi),
  86. Socioeconomic = as.numeric(Socioeconomic),
  87. Qualification = as.numeric(Qualification),
  88. sex = factor(sex),
  89. ethn = factor(ethn),
  90. Smoking_status = factor(Smoking_status),
  91. Alcohol_consumption = factor(Alcohol_consumption)
  92. ) %>%
  93. as.data.frame()
  94. dat[, meta_cols] <- lapply(dat[, meta_cols, drop = FALSE], function(x) {
  95. as.numeric(scale(as.numeric(x)))
  96. })
  97. dat <- fastDummies::dummy_cols(
  98. dat,
  99. select_columns = c("sex", "ethn", "Smoking_status", "Alcohol_consumption"),
  100. remove_first_dummy = TRUE,
  101. remove_selected_columns = TRUE,
  102. ignore_na = TRUE
  103. )
  104. dat
  105. }
  106. get_sem_covars <- function(dat) {
  107. c(
  108. "age", "Qualification", "bmi", "Socioeconomic",
  109. grep("^(sex_|ethn_|Smoking_status_|Alcohol_consumption_)",
  110. names(dat), value = TRUE)
  111. ) %>%
  112. unique() %>%
  113. intersect(names(dat))
  114. }
  115. remove_invalid_covars <- function(df, covars) {
  116. covars[vapply(covars, function(v) {
  117. x <- df[[v]]
  118. length(unique(x[!is.na(x)])) > 1
  119. }, logical(1))]
  120. }
  121. build_sem_model <- function(exposure, meta_cols, outcome, covars) {
  122. measurement_part <- paste0(
  123. "MetFactor =~ ",
  124. paste(meta_cols, collapse = " + ")
  125. )
  126. covar_rhs <- if (length(covars) > 0) {
  127. paste0(" + ", paste(covars, collapse = " + "))
  128. } else {
  129. ""
  130. }
  131. structural_part <- paste0(
  132. "\n",
  133. "MetFactor ~ a*", exposure, covar_rhs, "\n",
  134. outcome, " ~ b*MetFactor + cprime*", exposure, covar_rhs, "\n\n",
  135. "IE := a*b\n",
  136. "DE := cprime\n",
  137. "TE := cprime + (a*b)\n"
  138. )
  139. paste(measurement_part, structural_part, sep = "\n")
  140. }
  141. run_sem_latent <- function(dat, exposure, meta_cols,
  142. outcome = "migraine_incident",
  143. covars,
  144. estimator = "WLSMV") {
  145. use_vars <- unique(c(exposure, meta_cols, outcome, covars))
  146. df <- dat %>%
  147. select(all_of(use_vars)) %>%
  148. filter(complete.cases(.)) %>%
  149. as.data.frame()
  150. if (nrow(df) < 100 || length(unique(df[[outcome]])) < 2) {
  151. warning("Skipping ", exposure, ": insufficient complete cases or outcome variation.")
  152. return(NULL)
  153. }
  154. df[[exposure]] <- as.numeric(scale(as.numeric(df[[exposure]])))
  155. valid_covars <- remove_invalid_covars(df, covars)
  156. model <- build_sem_model(
  157. exposure = exposure,
  158. meta_cols = meta_cols,
  159. outcome = outcome,
  160. covars = valid_covars
  161. )
  162. fit <- lavaan::sem(
  163. model,
  164. data = df,
  165. ordered = outcome,
  166. estimator = estimator,
  167. std.lv = TRUE
  168. )
  169. pe <- lavaan::parameterEstimates(fit, standardized = TRUE) %>%
  170. as.data.frame()
  171. loadings <- pe %>%
  172. filter(op == "=~", lhs == "MetFactor") %>%
  173. transmute(
  174. Exposure = exposure,
  175. Metabolite_ID = rhs,
  176. Loading = est,
  177. SE = se,
  178. Z = z,
  179. P_value = pvalue,
  180. Std_loading = std.all,
  181. N = nrow(df)
  182. )
  183. effects <- pe %>%
  184. filter(
  185. (op == "~" & lhs %in% c("MetFactor", outcome)) |
  186. (op == ":=" & lhs %in% c("IE", "DE", "TE"))
  187. ) %>%
  188. mutate(
  189. Exposure = exposure,
  190. N = nrow(df)
  191. )
  192. fit_indices <- data.frame(
  193. Exposure = exposure,
  194. N = nrow(df),
  195. Chisq = lavaan::fitMeasures(fit, "chisq"),
  196. DF = lavaan::fitMeasures(fit, "df"),
  197. P_value = lavaan::fitMeasures(fit, "pvalue"),
  198. CFI = lavaan::fitMeasures(fit, "cfi"),
  199. TLI = lavaan::fitMeasures(fit, "tli"),
  200. RMSEA = lavaan::fitMeasures(fit, "rmsea"),
  201. SRMR = lavaan::fitMeasures(fit, "srmr")
  202. )
  203. list(
  204. exposure = exposure,
  205. model = model,
  206. fit = fit,
  207. loadings = loadings,
  208. effects = effects,
  209. fit_indices = fit_indices
  210. )
  211. }
  212. format_sem_tables <- function(sem_results, exposure_labels, meta_name_df) {
  213. valid_results <- compact(sem_results)
  214. loading_table <- bind_rows(map(valid_results, "loadings")) %>%
  215. left_join(meta_name_df, by = "Metabolite_ID") %>%
  216. mutate(
  217. Exposure = recode(Exposure, !!!as.list(exposure_labels)),
  218. Loading_95CI = sprintf(
  219. "%.4f (%.4f, %.4f)",
  220. Loading,
  221. Loading - 1.96 * SE,
  222. Loading + 1.96 * SE
  223. ),
  224. Direction = case_when(
  225. Std_loading > 0 ~ "Positive",
  226. Std_loading < 0 ~ "Negative",
  227. TRUE ~ "Neutral"
  228. )
  229. ) %>%
  230. select(
  231. Exposure, Metabolite_ID, Metabolite_name,
  232. Loading, SE, Z, P_value, Std_loading,
  233. Loading_95CI, Direction, N
  234. )
  235. effect_table <- bind_rows(map(valid_results, "effects")) %>%
  236. mutate(Exposure = recode(Exposure, !!!as.list(exposure_labels)))
  237. fit_table <- bind_rows(map(valid_results, "fit_indices")) %>%
  238. mutate(Exposure = recode(Exposure, !!!as.list(exposure_labels)))
  239. list(
  240. loadings = loading_table,
  241. effects = effect_table,
  242. fit_indices = fit_table
  243. )
  244. }
  245. # -----------------------------
  246. # Main analysis
  247. # -----------------------------
  248. required_vars <- c(
  249. "incident_migraine", "prevalent_depression", "prevalent_anxiety",
  250. "insomnia", "sleep duration", lasso_meta_cols, base_covars
  251. )
  252. check_required_vars(dat_base, required_vars)
  253. meta_name_df <- make_metabolite_map(lasso_meta_cols)
  254. dat_sem <- prepare_sem_data(dat_base, lasso_meta_cols)
  255. covars_sem <- get_sem_covars(dat_sem)
  256. sem_results <- lapply(names(exposures), function(expo) {
  257. tryCatch(
  258. run_sem_latent(
  259. dat = dat_sem,
  260. exposure = expo,
  261. meta_cols = lasso_meta_cols,
  262. outcome = "migraine_incident",
  263. covars = covars_sem,
  264. estimator = "WLSMV"
  265. ),
  266. error = function(e) {
  267. warning("SEM failed for ", expo, ": ", conditionMessage(e))
  268. NULL
  269. }
  270. )
  271. })
  272. names(sem_results) <- names(exposures)
  273. sem_tables <- format_sem_tables(sem_results, exposures, meta_name_df)
  274. # -----------------------------
  275. # Export results
  276. # -----------------------------
  277. fwrite(
  278. sem_tables$loadings,
  279. file.path(result_dir, "sem_latent_metabolite_factor_loadings.csv")
  280. )
  281. fwrite(
  282. sem_tables$effects,
  283. file.path(result_dir, "sem_model_based_association_parameters.csv")
  284. )
  285. fwrite(
  286. sem_tables$fit_indices,
  287. file.path(result_dir, "sem_fit_indices.csv")
  288. )
  289. saveRDS(
  290. sem_results,
  291. file.path(result_dir, "sem_latent_factor_results.rds")
  292. )
  293. message("SEM analysis completed. Results saved to: ", normalizePath(result_dir))

4.SEM.R at commit 0f4a3f2, no license · at the source

Overview

Authors: Yanggang Hong1,2, Feng Chen1,2, Yi Wang2, Xiu-Feng Huang1,2
ORCID iDs: Yanggang Hong
  1. The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
  2. Wenzhou Medical University, Wenzhou, Zhejiang, China
Journal: iScience, volume 29, issue 8, article 117031
Dates: received 4 May 2026; accepted 16 July 2026; published online 6 August 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1016/j.isci.2026.117031 · PMID 42602977 · PMCID PMC13475662 · OpenAlex W7196963832
Open access: gold, a free copy (OpenAlex)
Status: code verified
Categories: genetics / omics (modality), human (organism), pain (population), clinical / translational (subfield)
Methods: Statistics, Machine learning, Preprocessing, Physiology & signal measures
Keywords: migraine, metabolomics, plasma, lipoproteins, triglycerides
Topic: Migraine and Headache Studies (Psychiatry and Mental health, Medicine), according to OpenAlex
Citations: not cited yet (Europe PMC); 59 references in the paper

Abstract

Migraine has been linked to metabolic and vascular factors, and previous metabolomic studies have implicated HDL-related alterations, but large-scale prospective evidence remains limited. We analyzed 251 baseline plasma metabolites measured by nuclear magnetic resonance in 479,760 UK Biobank participants, including 6,724 incident hospital-diagnosed migraine cases during follow-up. Prospective and cross-sectional analyses replicated and extended a coherent lipid and lipoprotein pattern: HDL-related measures were generally inversely associated with hospital-diagnosed migraine, whereas triglyceride-rich and VLDL-related measures showed positive associations. Repeated least absolute shrinkage and selection operator (LASSO) analysis prioritized 12 metabolite features, which were further examined in exploratory analyses of brain structural imaging phenotypes, migraine polygenic risk, and affective and sleep-related traits. These findings provide large-scale prospective evidence supporting a structured plasma metabolomic profile associated with hospital-diagnosed migraine and contextualize systemic lipid and lipoprotein metabolism as a relevant domain for future mechanistic and translational studies of migraine-related metabolic variation.

Reproduced under the paper's license (CC BY), from the paper cited above.

Repository

Its files are read in the Code ↔ Paper reader above, with 9 matches between paragraphs and lines of code.

sun160414/UKB_Metabolomic_Migraine

License: none: the authors keep all their rights
State: the link answers, verified on 27 September 2026
Evidence: files inventoried
Commit: 0f4a3f2f88ad3f05812b088a146993ddd039aa19, 26 September 2026
Languages: R (5)
Size: 8 files, 5 scripts
Software Heritage: not archived
Found in: “Data and code availability”
Holds: README
Not found: license file, CITATION.cff, environment file, tests, continuous integration, documentation
Tools: data.table (3 files), ggplot2 (3 files), tidyverse (3 files), survival (2 files), circlize (1 file), ComplexHeatmap (1 file), lavaan (1 file), patchwork (1 file)
Availability: 1 check, the latest on 27 September 2026: the link answers
  • 27 September 2026: the link answers
6 files

The paper's code and data availability statement is in the Data section.

Tracing map

Proposed by the machine: these links were found in the paper and verified at the source, without human review. The map will receive a Zenodo DOI once one of the paper's authors has validated it with their ORCID.

What the map holds:

  • 1 repository of the authors' code, each at its verified commit, with its license and how the link was found in the paper;
  • 5 scripts, each with its path and the digest of its content;
  • 9 matches between paragraphs of the paper and lines of the code (method lexical-v1);
  • neither the text of the paper nor the code itself.

Its JSON (tracing-map.json) is deposited on Zenodo with its DOI once the map is validated.

Data

No dataset and no data link were found in the paper.

Data and code availability

• Individual-level UKB data used in this study are available to approved researchers through the UKB application system and cannot be publicly redistributed by the authors because of data-access restrictions. Detailed information on UKB data access is available through the UKB research access platform (https://www.ukbiobank.ac.uk/). • No new software was developed in this study. The analysis code used in this study is publicly available at https://github.com/sun160414/UKB_Metabolomic_Migraine. • All supplementary tables generated in this study are provided with the manuscript. Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon reasonable request.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 4 authors, 5 keywords, 59 references.

Cite

This paper

Hong, Y., Chen, F., Wang, Y., & Huang, X.-F. (2026). Plasma metabolomic signatures of migraine in 479,760 adults. iScience, 29(8), 117031. https://doi.org/10.1016/j.isci.2026.117031

BibTeX

@article{hong2026plasma,
author = {Hong, Yanggang and Chen, Feng and Wang, Yi and Huang, Xiu-Feng},
title = {{Plasma metabolomic signatures of migraine in 479,760 adults}},
journal = {iScience},
year = {2026},
month = aug,
volume = {29},
number = {8},
pages = {117031},
publisher = {Elsevier},
issn = {2589-0042},
doi = {10.1016/j.isci.2026.117031},
url = {https://doi.org/10.1016/j.isci.2026.117031},
pmid = {42602977},
pmcid = {PMC13475662}
}

RIS

TY - JOUR
AU - Hong, Yanggang
AU - Chen, Feng
AU - Wang, Yi
AU - Huang, Xiu-Feng
TI - Plasma metabolomic signatures of migraine in 479,760 adults
T2 - iScience
J2 - iScience
PY - 2026
DA - 2026/08/06
VL - 29
IS - 8
SP - 117031
SN - 2589-0042
PB - Elsevier
DO - 10.1016/j.isci.2026.117031
UR - https://doi.org/10.1016/j.isci.2026.117031
LA - en
ER -

CSL-JSON

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