Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels.
Large-scale meta-analyses of genome-wide association studies (GWAS) have identified >175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P < 5 × 10-8) three novel loci associated with HDL-C near CD163-APOBEC1 (P = 7.4 × 10-9), NCOA2 (P = 1.6 × 10-8), and NID2-PTGDR (P = 4.2 × 10-8), and one novel locus associated with TG near WDR11-FGFR2 (P = 2.7 × 10-10). Conditional analyses identified a second signal near CD163-APOBEC1. We then combined results from the East Asian meta-analysis with association results from up to 187,365 European individuals from the Global Lipids Genetics Consortium in a trans-ancestry meta-analysis. This analysis identified (log10Bayes Factor ≥6.1) eight additional novel lipid loci. Among the twelve total loci identified, the index variants at eight loci have demonstrated at least nominal significance with other metabolic traits in prior studies, and two loci exhibited coincident eQTLs (P < 1 × 10-5) in subcutaneous adipose tissue for BPTF and PDGFC. Taken together, these analyses identified multiple novel lipid loci, providing new potential therapeutic targets.
Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
Cassandra N
CN
Spracklen
Saw Swee Hock School of Public Health, National University Health System, National University of Singapore, Singapore, Singapore.|Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, China.
Peng
P
Chen
Division of Structural and Functional Genomics, Center for Genome Science, Korean National Institute of Health, Osong, Chungchungbuk-do, South Korea.
Young Jin
YJ
Kim
Life Sciences Institute, National University of Singapore, Singapore, Singapore.
Xu
X
Wang
Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Hui
H
Cai
Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA.
Shengxu
S
Li
Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Jirong
J
Long
Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
Ying
Y
Wu
Beijing Institute of Ophthalmology, Beijing Ophthalmology and Visual Science Key Lab, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Ya Xing
YX
Wang
National Center for Global Health and Medicine, Tokyo, Japan.
Fumihiko
F
Takeuchi
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.|School of Chinese Medicine, China Medical University, Taichung, Taiwan.
Jer-Yuarn
JY
Wu
Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, South Korea.
Keum-Ji
KJ
Jung
Shanghai Diabetes Institute, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, China.
Cheng
C
Hu
National Center for Global Health and Medicine, Tokyo, Japan.
Koichi
K
Akiyama
Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, China.
Yonghong
Y
Zhang
Division of Structural and Functional Genomics, Center for Genome Science, Korean National Institute of Health, Osong, Chungchungbuk-do, South Korea.
Sanghoon
S
Moon
Laboratory for Medical Science Mathematics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Todd A
TA
Johnson
Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, China.
Huaixing
H
Li
Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore.
Rajkumar
R
Dorajoo
Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Meian
M
He
Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
Maren E
ME
Cannon
Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
Tamara S
TS
Roman
Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Elias
E
Salfati
Department of Ophthalmology, Taichung Veterans General Hospital, Taichung, Taiwan.
Keng-Hung
KH
Lin
Department of Pediatrics, Institute for Translational Genomics and Population Sciences, LABioMed at Harbor-UCLA Medical Center, Torrance, CA, USA.
Xiuqing
X
Guo
Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.|School of Medicine, National Yang-Ming University, Taipei, Taiwan.|School of Medicine, National Defense Medical Center, Taipei, Taiwan.|Institute of Medical Technology, National Chung-Hsing University, Taichung, Taiwan.
Wayne H H
WHH
Sheu
HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA.
Devin
D
Absher
Department of Nutrition, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA.
Linda S
LS
Adair
Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Themistocles L
TL
Assimes
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.|Duke-NUS Medical School Singapore, Singapore, Singapore.|Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Tin
T
Aung
Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Qiuyin
Q
Cai
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Li-Ching
LC
Chang
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.|School of Chinese Medicine, China Medical University, Taichung, Taiwan.
Chien-Hsiun
CH
Chen
Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan.
Li-Hsin
LH
Chien
Division of Endocrinology & Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.|College of Medicine, National Taiwan University, Taipei, Taiwan.|Institute of Preventive Medicine, School of Public Health, National Taiwan University, Taipei, Taiwan.
Lee-Ming
LM
Chuang
Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan.
Shu-Chun
SC
Chuang
Department of Nutrition, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA.|Carolina Population Center, University of North Carolina, Chapel Hill, NC, USA.
Shufa
S
Du
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.
Qiao
Q
Fan
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Cathy S J
CSJ
Fann
USC-Office of Population Studies Foundation, Inc, University of San Carlos, Cebu City, Philippines.|Department of Anthropology, Sociology, and History, University of San Carlos, Cebu City, Philippines.
Alan B
AB
Feranil
Unit of Epidemiology, Hebrew University-Hadassah Braun School of Public Health, Jerusalem, Israel.
Yechiel
Y
Friedlander
Department of Nutrition, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA.|Carolina Population Center, University of North Carolina, Chapel Hill, NC, USA.
Penny
P
Gordon-Larsen
Department of Epidemiology and Population Genetics, Fuwai Hospital, Beijing, China.
Dongfeng
D
Gu
Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Lixuan
L
Gui
Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, China.
Zhirong
Z
Guo
Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.|Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore, Singapore.
Chew-Kiat
CK
Heng
Human Genetics Center, University of Texas School of Public Health, Houston, TX, USA.
James
J
Hixson
Shanghai Diabetes Institute, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, China.
Xuhong
X
Hou
Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan.
Chao Agnes
CA
Hsiung
Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, China.
Yao
Y
Hu
Division of Structural and Functional Genomics, Center for Genome Science, Korean National Institute of Health, Osong, Chungchungbuk-do, South Korea.
Mi Yeong
MY
Hwang
School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Chii-Min
CM
Hwu
National Center for Global Health and Medicine, Tokyo, Japan.
Masato
M
Isono
College of Medicine, National Taiwan University, Taipei, Taiwan.|Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Jyh-Ming Jimmy
JJ
Juang
Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore.|Department of Biochemistry, National University of Singapore, Singapore, Singapore.
Chiea-Chuen
CC
Khor
Division of Structural and Functional Genomics, Center for Genome Science, Korean National Institute of Health, Osong, Chungchungbuk-do, South Korea.
Yun Kyoung
YK
Kim
Saw Swee Hock School of Public Health, National University Health System, National University of Singapore, Singapore, Singapore.|Duke-NUS Medical School Singapore, Singapore, Singapore.
Woon-Puay
WP
Koh
RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Michiaki
M
Kubo
Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.|School of Medicine, National Yang-Ming University, Taipei, Taiwan.|School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
I-Te
IT
Lee
Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, South Korea.
Sun-Ju
SJ
Lee
Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.|Department of Social Work, Tunghai University, Taichung, Taiwan.
Wen-Jane
WJ
Lee
School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Cardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan.|Department of Medicine, China Medical University, Taichung, Taiwan.
Kae-Woei
KW
Liang
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.
Blanche
B
Lim
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.
Sing-Hui
SH
Lim
Saw Swee Hock School of Public Health, National University Health System, National University of Singapore, Singapore, Singapore.|Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore.|Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Jianjun
J
Liu
Department of Functional Pathology, Shimane University School of Medicine, Izumo, Japan.
Toru
T
Nabika
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Wen-Harn
WH
Pan
Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, China.
Hao
H
Peng
Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Thomas
T
Quertermous
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.|Duke-NUS Medical School Singapore, Singapore, Singapore.
Charumathi
C
Sabanayagam
Department of Pediatrics, Institute for Translational Genomics and Population Sciences, LABioMed at Harbor-UCLA Medical Center, Torrance, CA, USA.
Kevin
K
Sandow
Department of Genetics, Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center and Shanghai Industrial Technology Institute, Shanghai, China.
Jinxiu
J
Shi
Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, China.
Liang
L
Sun
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.
Pok Chien
PC
Tan
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.
Shu-Pei
SP
Tan
Department of Pediatrics, Institute for Translational Genomics and Population Sciences, LABioMed at Harbor-UCLA Medical Center, Torrance, CA, USA.
Kent D
KD
Taylor
Saw Swee Hock School of Public Health, National University Health System, National University of Singapore, Singapore, Singapore.|Life Sciences Institute, National University of Singapore, Singapore, Singapore.|Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore.|NUS Graduate School for Integrative Science and Engineering, National University of Singapore, Singapore, Singapore.|Department of Statistics and Applied Probability, National University of Singapore, Singapore, Singapore.
Yik-Ying
YY
Teo
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Sue-Anne
SA
Toh
Laboratory for Medical Science Mathematics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.|Department of Medical Science Mathematics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Tatsuhiko
T
Tsunoda
Saw Swee Hock School of Public Health, National University Health System, National University of Singapore, Singapore, Singapore.
Rob M
RM
van Dam
Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, China.
Aili
A
Wang
Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, China.
Feijie
F
Wang
Shanghai Diabetes Institute, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, China.
Jie
J
Wang
Beijing Tongren Eye Center, Beijing Tongren Hospital, Beijing Ophthalmology and Visual Science Key Lab, Beijing Key Laboratory of Intraocular Tumor Diagnosis and Treatment, Capital Medical University, Beijing, China.
Wen Bin
WB
Wei
Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China.
Yong-Bing
YB
Xiang
Department of Pediatrics, Institute for Translational Genomics and Population Sciences, LABioMed at Harbor-UCLA Medical Center, Torrance, CA, USA.
Jie
J
Yao
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.|Division of Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
Jian-Min
JM
Yuan
Shanghai Diabetes Institute, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, China.
Rong
R
Zhang
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.|Duke-NUS Medical School Singapore, Singapore, Singapore.
Wanting
W
Zhao
Department of Pediatrics, Institute for Translational Genomics and Population Sciences, LABioMed at Harbor-UCLA Medical Center, Torrance, CA, USA.
Yii-Der Ida
YI
Chen
Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA, USA.
Stephen S
SS
Rich
Department of Pediatrics, Institute for Translational Genomics and Population Sciences, LABioMed at Harbor-UCLA Medical Center, Torrance, CA, USA.
Jerome I
JI
Rotter
College of Medicine, National Taiwan University, Taipei, Taiwan.|Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Tzung-Dau
TD
Wang
Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Tangchun
T
Wu
Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, China.
Xu
X
Lin
Center for Genome Science, Korean National Institute of Health, Osong, Chungchungbuk-do, South Korea.
Bok-Ghee
BG
Han
Laboratory for Cardiovascular Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.|Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Toshihiro
T
Tanaka
Department of Biomedical Science, Hallym University, Chuncheon, South Korea.
Yoon Shin
YS
Cho
Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine, Suita, Japan.
Tomohiro
T
Katsuya
Shanghai Diabetes Institute, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, China.
Weiping
W
Jia
Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, South Korea.
Sun-Ha
SH
Jee
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Yuan-Tsong
YT
Chen
National Center for Global Health and Medicine, Tokyo, Japan.
Norihiro
N
Kato
Beijing Institute of Ophthalmology, Beijing Ophthalmology and Visual Science Key Lab, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China.|Department of Ophthalmology, Medical Faculty Mannheim of the Ruprecht-Karls-University of Heidelberg, Mannheim, Germany.
Jost B
JB
Jonas
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.|Duke-NUS Medical School Singapore, Singapore, Singapore.|Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Ching-Yu
CY
Cheng
Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Xiao-Ou
XO
Shu
Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA.
Jiang
J
He
Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Wei
W
Zheng
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.|Duke-NUS Medical School Singapore, Singapore, Singapore.|Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Tien-Yin
TY
Wong
Department of Genetics, Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center and Shanghai Industrial Technology Institute, Shanghai, China.
Wei
W
Huang
Division of Structural and Functional Genomics, Center for Genome Science, Korean National Institute of Health, Osong, Chungchungbuk-do, South Korea.
Bong-Jo
BJ
Kim
Saw Swee Hock School of Public Health, National University Health System, National University of Singapore, Singapore, Singapore.|Duke-NUS Medical School Singapore, Singapore, Singapore.|Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
E-Shyong
ES
Tai
Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
Karen L
KL
Mohlke
Saw Swee Hock School of Public Health, National University Health System, National University of Singapore, Singapore, Singapore.
Xueling
X
Sim
D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics; D002784:Cholesterol / Q000235:genetics* / Q000378:metabolism; D005006:Ethnicity; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies / Q000379:methods; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008055:Lipids / Q000235:genetics; D008075:Lipoproteins, HDL / Q000235:genetics; D008077:Lipoproteins, LDL / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D040641:Quantitative Trait Loci; D014280:Triglycerides / Q000235:genetics* / Q000378:metabolism; D044465:White People / Q000235:genetics
D008055:Lipids; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D014280:Triglycerides; D002784:Cholesterol