一项关于儿童体脂的全基因组关联研究。
A Genome-Wide Association Study of Childhood Body Fatness.
作者信息
Warner Erica T, Jiang Lai, Adjei David Nana, Turman Constance, Gordon William, Wang Lu, Tamimi Rulla, Kraft Peter, Lindström Sara
机构信息
Clinical Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
出版信息
Obesity (Silver Spring). 2021 Feb;29(2):446-453. doi: 10.1002/oby.23070.
OBJECTIVE
This study aimed to uncover genetic contributors to adiposity in early life.
METHODS
A genome-wide association study of childhood body fatness in 34,401 individuals within the Nurses' Health Studies and the Health Professionals Follow-up Study was conducted. Data were imputed to the 1000 Genomes Phase 3 version 5 reference panel.
RESULTS
A total of 1,354 single-nucleotide polymorphisms (P < 10 ) were selected for replication in a previously published genome-wide association study of childhood BMI. Nineteen significant genome-wide (P < 5 × 10 ) regions were observed, fourteen of which were previously associated with childhood obesity and five were novel: BNDF (P = 7.58 × 10 ), PRKD1 (P = 1.43 × 10 ), 20p13 (P = 2.05 × 10 ), FHIT (P = 1.77 × 10 ), and LOC101927575 (P = 3.22 × 10 ). The BNDF, FHIT, and PRKD1 regions were previously associated with adult BMI. LOC101927575 and 20p13 regions have not previously been associated with adiposity phenotypes. In a transcriptome-wide analysis, associations for POMC at 2p23.3 (P = 3.36 × 10 ) and with TMEM18 at 2p25.3 (P = 3.53 × 10 ) were observed. Childhood body fatness was genetically correlated with hip (r = 0.42, P = 4.44 × 10 ) and waist circumference (r = 0.39, P = 5.56 × 10 ), as well as age at menarche (r = -0.37, P = 7.96 × 10 ).
CONCLUSIONS
Additional loci that contribute to childhood adiposity were identified, further explicating its genetic architecture.
目的
本研究旨在揭示生命早期肥胖的遗传因素。
方法
在护士健康研究和卫生专业人员随访研究中，对34401名个体的儿童期体脂进行了全基因组关联研究。数据被推算到千人基因组计划第3阶段版本5参考面板。
结果
在先前发表的儿童BMI全基因组关联研究中，共选择了1354个单核苷酸多态性（P<10）进行重复验证。观察到19个全基因组显著（P<5×10）区域，其中14个区域先前与儿童肥胖相关，5个区域为新发现区域：脑源性神经营养因子（BNDF，P=7.58×10）、蛋白激酶D1（PRKD1，P=1.43×10）、20号染色体短臂13区（20p13，P=2.05×10）、脆性组氨酸三联体基因（FHIT，P=1.77×10）和LOC101927575（P=3.22×10）。BNDF、FHIT和PRKD1区域先前与成人BMI相关。LOC101927575和20p13区域先前未与肥胖表型相关。在全转录组分析中，观察到2号染色体短臂23.3区的阿黑皮素原（POMC，P=3.36×10）和2号染色体短臂25.3区的跨膜蛋白18（TMEM18，P=3.53×10）存在关联。儿童期体脂与臀围（r=0.4, P=4.44×10）、腰围（r=0.39, P=5.56×10）以及初潮年龄（r=-0.37, P=7.96×10）存在遗传相关性。
结论
确定了导致儿童肥胖的其他基因座，进一步阐明了其遗传结构。
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