Abstract MP068: Association Study of SNPs and measures of adiposity among 51990 European and European American Identifies Three Novel Loci
Notice bibliographique
Résumé
Introduction and objectives. Measures of adiposity such as waist circumference (WC) and waist-to-hip ratio (WHR) are associated with adverse cardiovascular events and diabetes independent of body mass index (BMI). WC and WHR have high heritability and multiple susceptibility loci have been identified across the genome, including GRB14 , LYPAL1 , and VEGFA . We aim to identify novel loci associated with WC and WHR using a bespoke SNP array focused on cardio-centric candidate genes. Methods. We assessed the association between SNPs and anthropometry phenotypes WC adjusted for BMI (cm), and WHR adjusted for BMI among 51990 individuals of European ancestry from NHLBI’s Candidate Gene Association Resource (CARe) project and 14 other cohorts. The study population consisted of women and men aged 20 to 80, of which 65% were females. Individuals were genotyped using the ITMAT/Broad/CARE (IBC) chip, which includes ∼50,000 densely mapped cosmopolitan tagged SNPs across ∼2100 candidate genes. We modeled each trait as a function of age, study site, and ancestry, and conducted a fixed-effects meta-analysis. Results. Three novel loci reached our Bonferroni adjusted threshold for statistical significance (P<2E-6). The A allele of SNP rs761422 in gene MFAP2 was associated with decreased WC adjusted for BMI (P=4.4E-7), and has previously been reported in a height GWAS. The C allele of SNP rs2811337 near TMCC1 , involved in signaling pathways, and the A allele of SNP rs7302703 in gene HOXC10 , involved in cell differentiation, were associated with decreased WHR adjusted for BMI (P=8.6E-9 and P=2.8E-7, respectively). Fourteen loci have been previously reported in association with WHR adjusted for BMI, five of which, were included on the IBC chip. Of the five, three also reached statistical significance with the same direction of effect in our sample: RSPO3 (P=3.0E-10), ADAMTS9 (P=8.6E-9),and ITPR2 (P=5.6E-8). All SNPs were common variants (MAF>10%). Fine mapping is currently underway to determine whether each locus may contain multiple independent signals. Replication cohorts have been identified and we are working to verify the novel loci and investigate sub-significant loci. Conclusions . In 51990 European decent individuals typed on a dense IBC chip, we identified 3 novel loci and replicated 3 additional loci. Significant loci among WC adjusted for BMI, and WHR adjusted for BMI were distinct from one another, indicating each measure of adiposity may be capturing distinct underlying phenotypes and thus different pathways through which risk alleles affect adiposity. We will pursue further assessment of risk loci and adiposity through fine mapping and follow-up genotyping.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,002 | 0,003 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,001 | 0,002 |
| Études des sciences et des technologies | 0,001 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,005 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».