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Rare, low frequency and common coding variants in CHRNA5 and their contribution to nicotine dependence in European and African Americans.

TitleRare, low frequency and common coding variants in CHRNA5 and their contribution to nicotine dependence in European and African Americans.
Publication TypeJournal Article
Year of Publication2016
AuthorsOlfson E, Saccone NL, Johnson EO, Chen L-S, Culverhouse R, Doheny K, Foltz SM, Fox L, Gogarten SM, Hartz S, Hetrick K, Laurie CC, Marosy B, Amin N, Arnett D, Barr RG, Bartz TM, Bertelsen S, Borecki IB, Brown MR, Chasman DI, van Duijn CM, Feitosa MF, Fox ER, Franceschini N, Franco OH, Grove ML, Guo X, Hofman A, Kardia SLR, Morrison AC, Musani SK, Psaty BM, Rao DC, Reiner AP, Rice K, Ridker PM, Rose LM, Schick UM, Schwander K, Uitterlinden AG, Vojinovic D, Wang J-C, Ware EB, Wilson G, Yao J, Zhao W, Breslau N, Hatsukami D, Stitzel JA, Rice J, Goate A
Secondary AuthorsBierut LJ
JournalMol Psychiatry
Volume21
Issue5
Pagination601-7
Date Published2016 May
ISSN1476-5578
KeywordsAdult, African Americans, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Genetic Variation, Humans, Male, Middle Aged, Nerve Tissue Proteins, Receptors, Nicotinic, Tobacco Use Disorder
Abstract

The common nonsynonymous variant rs16969968 in the α5 nicotinic receptor subunit gene (CHRNA5) is the strongest genetic risk factor for nicotine dependence in European Americans and contributes to risk in African Americans. To comprehensively examine whether other CHRNA5 coding variation influences nicotine dependence risk, we performed targeted sequencing on 1582 nicotine-dependent cases (Fagerström Test for Nicotine Dependence score⩾4) and 1238 non-dependent controls, with independent replication of common and low frequency variants using 12 studies with exome chip data. Nicotine dependence was examined using logistic regression with individual common variants (minor allele frequency (MAF)⩾0.05), aggregate low frequency variants (0.05>MAF⩾0.005) and aggregate rare variants (MAF

DOI10.1038/mp.2015.105
Alternate JournalMol Psychiatry
PubMed ID26239294
PubMed Central IDPMC4740321
Grant ListHHSN268201100012C / HL / NHLBI NIH HHS / United States
U10 HL054472 / HL / NHLBI NIH HHS / United States
U01 HL054472 / HL / NHLBI NIH HHS / United States
UL1RR025005 / RR / NCRR NIH HHS / United States
R01 NS041558 / NS / NINDS NIH HHS / United States
RC2 HL102419 / HL / NHLBI NIH HHS / United States
R01HL085251 / HL / NHLBI NIH HHS / United States
U01 HL054471 / HL / NHLBI NIH HHS / United States
R01 HL103612 / HL / NHLBI NIH HHS / United States
HHSN268201100001I / HL / NHLBI NIH HHS / United States
F30AA023685 / AA / NIAAA NIH HHS / United States
HHSN268201100009I / HL / NHLBI NIH HHS / United States
U19 CA148127 / CA / NCI NIH HHS / United States
U01 HL054496 / HL / NHLBI NIH HHS / United States
U01HL54473 / HL / NHLBI NIH HHS / United States
U10 HL054497 / HL / NHLBI NIH HHS / United States
UL1TR000124 / TR / NCATS NIH HHS / United States
UC2 HL103010 / HL / NHLBI NIH HHS / United States
U10AA008401 / AA / NIAAA NIH HHS / United States
HL054481 / HL / NHLBI NIH HHS / United States
N01HC95160 / HL / NHLBI NIH HHS / United States
5RC2HL102419 / HL / NHLBI NIH HHS / United States
R01 HL071251 / HL / NHLBI NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States
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HHSN268201100010C / HL / NHLBI NIH HHS / United States
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UL1 RR025005 / RR / NCRR NIH HHS / United States
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HL118305 / HL / NHLBI NIH HHS / United States
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P30 DK063491 / DK / NIDDK NIH HHS / United States
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T32 GM007200 / GM / NIGMS NIH HHS / United States
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HHSN268201100005I / HL / NHLBI NIH HHS / United States
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HHSN271201100004C / AG / NIA NIH HHS / United States
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HHSN268201100002C / WH / WHI NIH HHS / United States
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UL1TR000040 / TR / NCATS NIH HHS / United States
HL54473 / HL / NHLBI NIH HHS / United States
HL054457 / HL / NHLBI NIH HHS / United States
R01 CA047988 / CA / NCI NIH HHS / United States
N01 HC095165 / HC / NHLBI NIH HHS / United States
UL1 TR000448 / TR / NCATS NIH HHS / United States
NS041558 / NS / NINDS NIH HHS / United States
TL1TR000449 / TR / NCATS NIH HHS / United States
R01DK089256 / DK / NIDDK NIH HHS / United States
R21 HL123677 / HL / NHLBI NIH HHS / United States
R01 HL080467 / HL / NHLBI NIH HHS / United States
R01HL087652 / HL / NHLBI NIH HHS / United States
N01HC85082 / HL / NHLBI NIH HHS / United States
R01 DK089256 / DK / NIDDK NIH HHS / United States
N01HC95167 / HL / NHLBI NIH HHS / United States
TL1 TR000449 / TR / NCATS NIH HHS / United States
R01HL55673 / HL / NHLBI NIH HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
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N01HC85083 / HL / NHLBI NIH HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
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N01 HC095168 / HC / NHLBI NIH HHS / United States
U01 HL054481 / HL / NHLBI NIH HHS / United States
DK063491 / DK / NIDDK NIH HHS / United States
RC2 HL103010 / HL / NHLBI NIH HHS / United States
HHSN268201100007I / HL / NHLBI NIH HHS / United States
UL1 TR000040 / TR / NCATS NIH HHS / United States
HHSN268201300046C / HL / NHLBI NIH HHS / United States
U10 HL054473 / HL / NHLBI NIH HHS / United States
HHSN268201100002I / HL / NHLBI NIH HHS / United States
U10 AA008401 / AA / NIAAA NIH HHS / United States
U10 HL054495 / HL / NHLBI NIH HHS / United States
U01HL080295 / HL / NHLBI NIH HHS / United States
N01 HC095163 / HC / NHLBI NIH HHS / United States
R01HL071259 / HL / NHLBI NIH HHS / United States
U10 HL054496 / HL / NHLBI NIH HHS / United States
U10 HL054471 / HL / NHLBI NIH HHS / United States
HL54495 / HL / NHLBI NIH HHS / United States
R01HL103612 / HL / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
N01 HC085079 / HC / NHLBI NIH HHS / United States
N01HC95166 / HL / NHLBI NIH HHS / United States
R01HL071251 / HL / NHLBI NIH HHS / United States
R01 HL117078 / HL / NHLBI NIH HHS / United States
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HL119443 / HL / NHLBI NIH HHS / United States
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HHSN268201100001C / WH / WHI NIH HHS / United States
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R01 HL055673 / HL / NHLBI NIH HHS / United States
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F30 AA023685 / AA / NIAAA NIH HHS / United States
N01 HC095159 / HC / NHLBI NIH HHS / United States
R01HL120393 / HL / NHLBI NIH HHS / United States
N01HC85081 / HL / NHLBI NIH HHS / United States
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