title: A sequencing-based survey of functional APAF1 alleles in a large sample of individuals with affective illness and population controls.
abstract: Rare apoptosis-promoting functional variants in the apoptosis protease activating factor 1 (APAF1) gene were recently reported to co-segregate with major depression in male members of families from Utah. In order to estimate the impact of these variants on risk for major depressive disorder (MDD) in the general population, we surveyed the frequency of the APAF1 putative MDD risk alleles using re-sequencing in a large sample of northern European and European-American subjects, including a large number of males with MDD. The E777K and N782T APAF1 variants previously described by Harlan et al. [Harlan et al. (2006) Mol Psychiatry 11(1):76-85] were found at low frequencies in affected individuals and population controls. The C450W and Q465R variants were not detected in any of the 632 subjects sequenced. These results show that the APAF1 variants associated with risk for MDD in the Utah pedigrees are very rare in Northern European and European-American populations. In addition, the E777K and N782T variants were found at low frequencies both in patients and population controls, suggesting that these variants have limited impact on risk for MDD.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Zenab
authors.initials: Z
authors.lastname: Amin
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kanarek
authors.forename: Evgeny
authors.initials: E
authors.lastname: Krupitsky
authors.forename: Espen
authors.initials: E
authors.lastname: Walderhaug
authors.forename: Risto
authors.initials: R
authors.lastname: Ilomäki
authors.forename: Hilary
authors.initials: H
authors.lastname: Blumberg
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Price
authors.forename: Zubin
authors.initials: Z
authors.lastname: Bhagwagar
authors.forename: Linda L
authors.initials: LL
authors.lastname: Carpenter
authors.forename: Audrey R
authors.initials: AR
authors.lastname: Tyrka
authors.forename: Andres
authors.initials: A
authors.lastname: Magnusson
authors.forename: Nils Inge
authors.initials: NI
authors.lastname: Landrø
authors.forename: Edwin
authors.initials: E
authors.lastname: Zvartau
authors.forename: Joel
authors.initials: J
authors.lastname: Gelernter
authors.forename: C Neill
authors.initials: CN
authors.lastname: Epperson
authors.forename: Pirkko
authors.initials: P
authors.lastname: Räsänen
authors.forename: Jari
authors.initials: J
authors.lastname: Siironen
authors.forename: Jaakko
authors.initials: J
authors.lastname: Lappalainen
mesh_terms: D000483:Alleles; D053477:Apoptotic Protease-Activating Factor 1 / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers; D003865:Major Depressive Disorder / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D044382:Population Groups
chemical_list: C506592:APAF1 protein, human; D053477:Apoptotic Protease-Activating Factor 1; D017931:DNA Primers