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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 Feb 15
ISSN1460-2083
KeywordsAged, Chromosome Mapping, Female, Ferrochelatase, genome-wide association study, Genotype, Hispanic or Latino, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Polysomnography, Sleep Apnea, Obstructive, White People
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
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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
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HHSN268201100011C / HL / NHLBI NIH HHS / United States
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MS#: 
0511
Manuscript Lead/Corresponding Author Affiliation: 
Affiliated Investigator - Not at HCHS/SOL site
ECI: 
Yes
Manuscript Affiliation: 
Coordinating Center - Collaborative Studies Coordinating Center - UNC at Chapel Hill
Manuscript Status: 
Published