Accessibility issues or difficulties with this website?
Call 919-962-2073 or email hchsadministration@unc.edu.

Admixture mapping identifies novel loci for obstructive sleep apnea in Hispanic/Latino Americans.

TitleAdmixture mapping identifies novel loci for obstructive sleep apnea in Hispanic/Latino Americans.
Publication TypePublication
Year2019
AuthorsWang H, Cade BE, Sofer T, Sands SA, Chen H, Browning SR, Stilp AM, Louie TL, Thornton TA, W Johnson C, Below JE, Conomos MP, Evans DS, Gharib SA, Guo X, Wood AC, Mei H, Yaffe K, Loredo JS, Ramos AR, Barrett-Connor E, Ancoli-Israel S, Zee PC, Arens R, Shah NA, Taylor KD, Tranah GJ, Stone KL, Hanis CL, Wilson JG, Gottlieb DJ, Patel SR, Rice K, Post WS, Rotter JI, Sunyaev SR, Cai J, Lin X, Purcell SM, Laurie CC, Saxena R, Redline S, Zhu X
JournalHum Mol Genet
Volume28
Issue4
Pagination675-687
Date Published2019 02 15
ISSN1460-2083
KeywordsAged, Chromosome Mapping, European Continental Ancestry Group, Female, Ferrochelatase, genome-wide association study, Genotype, Hispanic Americans, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Polysomnography, Sleep Apnea, Obstructive
Abstract

Obstructive sleep apnea (OSA) is a common disorder associated with increased risk of cardiovascular disease and mortality. Its prevalence and severity vary across ancestral background. Although OSA traits are heritable, few genetic associations have been identified. To identify genetic regions associated with OSA and improve statistical power, we applied admixture mapping on three primary OSA traits [the apnea hypopnea index (AHI), overnight average oxyhemoglobin saturation (SaO2) and percentage time SaO2 < 90%] and a secondary trait (respiratory event duration) in a Hispanic/Latino American population study of 11 575 individuals with significant variation in ancestral background. Linear mixed models were performed using previously inferred African, European and Amerindian local genetic ancestry markers. Global African ancestry was associated with a lower AHI, higher SaO2 and shorter event duration. Admixture mapping analysis of the primary OSA traits identified local African ancestry at the chromosomal region 2q37 as genome-wide significantly associated with AHI (P < 5.7 × 10-5), and European and Amerindian ancestries at 18q21 suggestively associated with both AHI and percentage time SaO2 < 90% (P < 10-3). Follow-up joint ancestry-SNP association analyses identified novel variants in ferrochelatase (FECH), significantly associated with AHI and percentage time SaO2 < 90% after adjusting for multiple tests (P < 8 × 10-6). These signals contributed to the admixture mapping associations and were replicated in independent cohorts. In this first admixture mapping study of OSA, novel associations with variants in the iron/heme metabolism pathway suggest a role for iron in influencing respiratory traits underlying OSA.

DOI10.1093/hmg/ddy387
Alternate JournalHum Mol Genet
PubMed ID30403821
PubMed Central IDPMC6360325
Grant ListHHSN268201100010C / HL / NHLBI NIH HHS / United States
UL1 TR000128 / TR / NCATS NIH HHS / United States
HHSN268201200036C / HL / NHLBI NIH HHS / United States
KL2 RR024990 / RR / NCRR NIH HHS / United States
U01 AG027810 / AG / NIA NIH HHS / United States
U01 DK085501 / DK / NIDDK NIH HHS / United States
HHSN268201100012C / HL / NHLBI NIH HHS / United States
UL1 RR033176 / RR / NCRR NIH HHS / United States
HHSN268201300005C / HL / NHLBI NIH HHS / United States
HHSN268201100009I / HL / NHLBI NIH HHS / United States
HHSN268201500003C / HL / NHLBI NIH HHS / United States
P50 HL056984 / HL / NHLBI NIH HHS / United States
R01 HG003054 / HG / NHGRI NIH HHS / United States
N01HC95160 / HL / NHLBI NIH HHS / United States
HHSN263201500003I / NH / NIH HHS / United States
R01 HL070848 / HL / NHLBI NIH HHS / United States
R01 HL046380 / HL / NHLBI NIH HHS / United States
R01 HL071194 / HL / NHLBI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
N01HC95163 / HL / NHLBI NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
UL1 TR001079 / TR / NCATS NIH HHS / United States
HHSN268201100005G / HL / NHLBI NIH HHS / United States
R01 HL070847 / HL / NHLBI NIH HHS / United States
HHSN268201100008I / HL / NHLBI NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
N01 HC015103 / HC / NHLBI NIH HHS / United States
R01 HL085251 / HL / NHLBI NIH HHS / United States
N01HC95169 / HL / NHLBI NIH HHS / United States
R01 HL113338 / HL / NHLBI NIH HHS / United States
HHSN268201100011I / HL / NHLBI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
N01 HC085084 / HC / NHLBI NIH HHS / United States
N01HC65236 / HL / NHLBI NIH HHS / United States
N01 HC085085 / HC / NHLBI NIH HHS / United States
R01 HL070842 / HL / NHLBI NIH HHS / United States
HHSN268201300048C / HL / NHLBI NIH HHS / United States
U01 AG042124 / AG / NIA NIH HHS / United States
N01HC65235 / HL / NHLBI NIH HHS / United States
R01 HL087652 / HL / NHLBI NIH HHS / United States
N01HC95164 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
U01 AG042145 / AG / NIA NIH HHS / United States
N01HC95162 / HL / NHLBI NIH HHS / United States
R01 DK107859 / DK / NIDDK NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
N01HC65234 / HL / NHLBI NIH HHS / United States
N02 HL64278 / HL / NHLBI NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
N01HC95168 / HL / NHLBI NIH HHS / United States
R01 HL102830 / HL / NHLBI NIH HHS / United States
R01 DK073541 / DK / NIDDK NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
R35 HL135818 / HL / NHLBI NIH HHS / United States
R01 HL098433 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
N01HC65233 / HL / NHLBI NIH HHS / United States
HHSN268201300049C / HL / NHLBI NIH HHS / United States
U01 HL053941 / HL / NHLBI NIH HHS / United States
N01HC65237 / HL / NHLBI NIH HHS / United States
HHSN268201100005I / HL / NHLBI NIH HHS / United States
U01 AG042168 / AG / NIA NIH HHS / United States
N01HC95165 / HL / NHLBI NIH HHS / United States
N01HC95159 / HL / NHLBI NIH HHS / United States
R01 HL070841 / HL / NHLBI NIH HHS / United States
N01HC95161 / HL / NHLBI NIH HHS / United States
HHSN268201300047C / HL / NHLBI NIH HHS / United States
UL1 TR001420 / TR / NCATS NIH HHS / United States
U01 AG042140 / AG / NIA NIH HHS / United States
R01 HL070838 / HL / NHLBI NIH HHS / United States
HHSN268201300050C / HL / NHLBI NIH HHS / United States
R01 AR051124 / AR / NIAMS NIH HHS / United States
R01 AI085014 / AI / NIAID NIH HHS / United States
N01HC85082 / HL / NHLBI NIH HHS / United States
N01HC75150 / HL / NHLBI NIH HHS / United States
N01HC95167 / HL / NHLBI NIH HHS / United States
R01 HL070839 / HL / NHLBI NIH HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
N01HC85083 / HL / NHLBI NIH HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
RC2 AR058973 / AR / NIAMS 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
N01HC95166 / HL / NHLBI NIH HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States
N01 HC045133 / HC / NHLBI NIH HHS / United States
N01HC85080 / HL / NHLBI NIH HHS / United States
R01 HL070837 / HL / NHLBI NIH HHS / United States
U54 GM115428 / GM / NIGMS NIH HHS / United States
N01 HC035129 / HC / NHLBI NIH HHS / United States
U01 AG042143 / AG / NIA NIH HHS / United States
U01 AG042139 / AG / NIA NIH HHS / United States
P30 DK020595 / DK / NIDDK NIH HHS / United States
N01HC85081 / HL / NHLBI NIH HHS / United States
K01 HL135405 / HL / NHLBI NIH HHS / United States
U01 AR066160 / AR / NIAMS NIH HHS / United States
MS#: 
0511
Manuscript Lead/Corresponding Author Affiliation: 
Affiliated Investigator - Not at HCHS/SOL site
ECI: 
Manuscript Affiliation: 
Coordinating Center - Collaborative Studies Coordinating Center - UNC at Chapel Hill
Manuscript Status: 
Published