2019
CELA2A mutations predispose to early-onset atherosclerosis and metabolic syndrome and affect plasma insulin and platelet activation
Esteghamat F, Broughton JS, Smith E, Cardone R, Tyagi T, Guerra M, Szabó A, Ugwu N, Mani MV, Azari B, Kayingo G, Chung S, Fathzadeh M, Weiss E, Bender J, Mane S, Lifton RP, Adeniran A, Nathanson MH, Gorelick FS, Hwa J, Sahin-Tóth M, Belfort-DeAguiar R, Kibbey RG, Mani A. CELA2A mutations predispose to early-onset atherosclerosis and metabolic syndrome and affect plasma insulin and platelet activation. Nature Genetics 2019, 51: 1233-1243. PMID: 31358993, PMCID: PMC6675645, DOI: 10.1038/s41588-019-0470-3.Peer-Reviewed Original ResearchConceptsEarly-onset atherosclerosisMetabolic syndromeMetabolic syndrome traitsWhole-exome sequence analysisAttractive therapeutic targetPlatelet hyperactivationInsulin levelsPlasma insulinPlasma levelsInsulin sensitivityInsulin secretionTherapeutic targetPlatelet activationDisease mechanismsSyndrome traitsAtherosclerosisFunction mutationsSyndromeNovel lossInsulinMutationsSecretion
2016
Mutations in the Histone Modifier PRDM6 Are Associated with Isolated Nonsyndromic Patent Ductus Arteriosus
Li N, Subrahmanyan L, Smith E, Yu X, Zaidi S, Choi M, Mane S, Nelson-Williams C, Behjati M, Kazemi M, Hashemi M, Fathzadeh M, Narayanan A, Tian L, Montazeri F, Mani M, Begleiter ML, Coon BG, Lynch HT, Olson EN, Zhao H, Ruland J, Lifton RP, Mani A. Mutations in the Histone Modifier PRDM6 Are Associated with Isolated Nonsyndromic Patent Ductus Arteriosus. American Journal Of Human Genetics 2016, 98: 1082-1091. PMID: 27181681, PMCID: PMC4908195, DOI: 10.1016/j.ajhg.2016.03.022.Peer-Reviewed Original ResearchConceptsVascular smooth muscle cellsHistone methyl transferase activityWhole-exome sequencingGenome-wide linkage analysisWild-type proteinPatent ductus arteriosusMethyl transferase activityEpigenetic regulationLoss of functionTranscriptional suppressorNuclear proteinsPremature differentiationMethyltransferase activityCommon congenital heart defectUndifferentiated stageIndependent mutationsDuctus arteriosusLinkage analysisIntracellular redistributionNumber of VSMCsPRDM6Smooth muscle cellsProteinMutationsDisease mechanismsMetabolic syndrome
Ziki M, Mani A. Metabolic syndrome. Current Opinion In Lipidology 2016, 27: 162-171. PMID: 26825138, PMCID: PMC5141383, DOI: 10.1097/mol.0000000000000276.Peer-Reviewed Original ResearchConceptsMetabolic traitsGenome-wide association studiesCognate pathwaysDiverse traitsMultifactorial heritabilityDisease genesAssociation studiesGenetic studiesTraitsGenetic investigationsCommon variantsDisease mechanismsGenetic causeGenetic risk factorsHomogenous populationDisease pathophysiologyQuantitative distributionGenesVariantsHeritabilityExtreme endsSubstantial progressKindredsPathwayLarge effect