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Genome-wide association study of body fat distribution traits in Hispanics/Latinos from the HCHS/SOL.

TitleGenome-wide association study of body fat distribution traits in Hispanics/Latinos from the HCHS/SOL.
Publication TypePublication
Year2021
AuthorsJustice AE, Young K, Gogarten SM, Sofer T, Graff M, Love SAnn M, Wang Y, Klimentidis YC, Cruz M, Guo X, Hartwig F, Petty L, Yao J, Allison MA, Below JE, Buchanan TA, Chen Y-DIda, Goodarzi MO, Hanis C, Highland HM, Hsueh WA, Ipp E, Parra E, Palmas W, Raffel LJ, Rotter JI, Tan J, Taylor KD, Valladares A, Xiang AH, Sanchez-Johnsen L, Isasi CR, North KE
JournalHum Mol Genet
Volume30
Issue22
Pagination2190-2204
Date Published2021 11 01
ISSN1460-2083
Keywordsadiposity, Alleles, Body Fat Distribution, genome-wide association study, Hispanic or Latino, Humans, Polymorphism, Single Nucleotide, Quantitative Trait, Heritable
Abstract

Central obesity is a leading health concern with a great burden carried by ethnic minority populations, especially Hispanics/Latinos. Genetic factors contribute to the obesity burden overall and to inter-population differences. We aimed to identify the loci associated with central adiposity measured as waist-to-hip ratio (WHR), waist circumference (WC) and hip circumference (HIP) adjusted for body mass index (adjBMI) by using the Hispanic Community Health Study/Study of Latinos (HCHS/SOL); determine if differences in associations differ by background group within HCHS/SOL and determine whether previously reported associations generalize to HCHS/SOL. Our analyses included 7472 women and 5200 men of mainland (Mexican, Central and South American) and Caribbean (Puerto Rican, Cuban and Dominican) background residing in the USA. We performed genome-wide association analyses stratified and combined across sexes using linear mixed-model regression. We identified 16 variants for waist-to-hip ratio adjusted for body mass index (WHRadjBMI), 22 for waist circumference adjusted for body mass index (WCadjBMI) and 28 for hip circumference adjusted for body mass index (HIPadjBMI), which reached suggestive significance (P < 1 × 10-6). Many loci exhibited differences in strength of associations by ethnic background and sex. We brought a total of 66 variants forward for validation in cohorts (N = 34 161) with participants of Hispanic/Latino, African and European descent. We confirmed four novel loci (P < 0.05 and consistent direction of effect, and P < 5 × 10-8 after meta-analysis), including two for WHRadjBMI (rs13301996, rs79478137); one for WCadjBMI (rs3168072) and one for HIPadjBMI (rs28692724). Also, we generalized previously reported associations to HCHS/SOL, (8 for WHRadjBMI, 10 for WCadjBMI and 12 for HIPadjBMI). Our study highlights the importance of large-scale genomic studies in ancestrally diverse Hispanic/Latino populations for identifying and characterizing central obesity susceptibility that may be ancestry-specific.

DOI10.1093/hmg/ddab166
Alternate JournalHum Mol Genet
PubMed ID34165540
PubMed Central IDPMC8561424
Grant ListN01HC65236 / HL / NHLBI NIH HHS / United States
HHSN268201300005C / HL / NHLBI NIH HHS / United States
P01 HL060030 / HL / NHLBI NIH HHS / United States
HHSN268201700005I / HL / NHLBI NIH HHS / United States
P30 DK020541 / DK / NIDDK NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
HHSN261201300005I / CA / NCI NIH HHS / United States
R01 HL149683 / HL / NHLBI NIH HHS / United States
HHSN268201000001I / HL / NHLBI NIH HHS / United States
HHSN268201100001C / WH / WHI NIH HHS / United States
HHSN268201000031C / HL / NHLBI NIH HHS / United States
75N92020C00007 / HL / NHLBI NIH HHS / United States
N01HC95169 / HL / NHLBI NIH HHS / United States
K99 HL130580 / HL / NHLBI NIH HHS / United States
R01 HL088457 / HL / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
N01HC95161 / HL / NHLBI NIH HHS / United States
R01 HL136528 / HL / NHLBI NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States
75N92020C00005 / HL / NHLBI NIH HHS / United States
HHSN268201700001I / HL / NHLBI NIH HHS / United States
R01 HL050050 / HL / NHLBI NIH HHS / United States
N01HC95168 / HL / NHLBI NIH HHS / United States
N01HC65237 / HL / NHLBI NIH HHS / United States
R00 HL130580 / HL / NHLBI NIH HHS / United States
N01HC65234 / HL / NHLBI NIH HHS / United States
HHSN271201100004C / AG / NIA NIH HHS / United States
R01 HL142302 / HL / NHLBI NIH HHS / United States
HHSN268201700004I / HL / NHLBI NIH HHS / United States
N01HC95162 / HL / NHLBI NIH HHS / United States
R01 HL067974 / HL / NHLBI NIH HHS / United States
UL1 TR001420 / TR / NCATS NIH HHS / United States
HHSN261201300004I / CA / NCI NIH HHS / United States
HHSN268201000021C / HL / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
75N90020D00002 / CL / CLC NIH HHS / United States
N01HC65235 / HL / NHLBI NIH HHS / United States
T32 HL129982 / HL / NHLBI NIH HHS / United States
N01HC95165 / HL / NHLBI NIH HHS / United States
N01HC65233 / HL / NHLBI NIH HHS / United States
HHSN268201100004C / WH / WHI NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
N01HC95167 / HL / NHLBI NIH HHS / United States
P30 ES030285 / ES / NIEHS NIH HHS / United States
HHSN268201700002I / HL / NHLBI NIH HHS / United States
N01HC95159 / HL / NHLBI NIH HHS / United States
N01HC95163 / HL / NHLBI NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
75N92020C00001 / HL / NHLBI NIH HHS / United States
75N90020D00003 / CL / CLC NIH HHS / United States
HHSN268201700003I / HL / NHLBI NIH HHS / United States
HHSN268201500003I / HL / NHLBI NIH HHS / United States
HHSN268201100046C / HL / NHLBI NIH HHS / United States
HHSN268201100003C / WH / WHI NIH HHS / United States
N01HC95164 / HL / NHLBI NIH HHS / United States
R01 DK124097 / DK / NIDDK NIH HHS / United States
75N95020D00004 / DA / NIDA NIH HHS / United States
UL1 TR001079 / TR / NCATS NIH HHS / United States
UL1 TR000040 / TR / NCATS NIH HHS / United States
P60 DK020541 / DK / NIDDK NIH HHS / United States
N01HC95166 / HL / NHLBI NIH HHS / United States
HHSN268201100002C / WH / WHI NIH HHS / United States
75N92020C00006 / HL / NHLBI NIH HHS / United States
T32 HL007055 / HL / NHLBI NIH HHS / United States
N01HC95160 / HL / NHLBI NIH HHS / United States
MS#: 
0315
Manuscript Lead/Corresponding Author Affiliation: 
HCHS/SOL Genetic Analysis Center - University of Washington, Seattle
ECI: 
Yes
Manuscript Status: 
Published