Birth weight modifies the association between central nervous system gene variation and adult body mass index.
Birth weight modifies the association between central nervous system gene variation and adult body mass index.
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DOI：
10.1038/jhg.2015.139
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发表时间：
2016-03
影响因子：
3.5
通讯作者：
Palmer JR
中科院分区：
文献类型：
--
作者：
Ruiz-Narváez EA;Haddad SA;Rosenberg L;Palmer JR
全基因组关联研究（GWAS）已经确定了大约100个与体重指数（BMI）相关的基因座。出生体重低的人患代谢紊乱的风险增加。我们推测，正常的体重调节机制在低出生体重的受试者中被破坏。目前的分析包括2215名来自黑人妇女健康研究的非裔美国妇女，并基于20个BMI相关基因座的基因型数据和自我报告的出生体重、18岁体重和成年体重数据。我们使用一般线性模型来评估个体SNPs与18岁时和成年后出生体重分层（高于和低于中位数，3200 g）中BMI的相关性。三个SNP（TMEM 18附近的rs 1320330，PCSK 1附近的rs 261967和FTO中的rs 17817964）以及结合这三个变体的遗传评分显示出与出生体重和BMI的显著相互作用。在出生体重<3200 g的女性中，遗传评分与BMI之间存在负相关; 18岁时BMI的β系数=-0.045（95% CI-0.104，0.013），成人BMI的β系数=-0.055（95% CI-0.112，0.002）。在出生体重≥ 3，200 g的女性中，遗传评分与BMI呈正相关：18岁时BMI的β系数= 0.110（95% CI 0.051，0.169）（相互作用P = 0.0002），成人BMI为0.112（95% CI 0.054，0.170）（相互作用P < 0.0001）。由于TMEM 18、PCSK 1和FTO在中枢神经系统（CNS）中高度表达，我们的研究结果表明，低出生体重可能会破坏CNS体重调节机制。
Genome wide association studies (GWAS) have identified approximately 100 loci associated with body mass index (BMI). Persons with low birth-weight have an increased risk of metabolic disorders. We postulate that normal mechanisms of body weight regulation are disrupted in subjects with low birth-weight. The present analyses included 2215 African American women from the Black Women’s Health Study, and were based on genotype data on twenty BMI-associated loci and self-reported data on birth-weight, weight at age 18, and adult weight. We used general linear models to assess the association of individual SNPs with BMI at age 18 and later in adulthood within strata of birth-weight (above and below the median, 3200 g). Three SNPs (rs1320330 near TMEM18, rs261967 near PCSK1, and rs17817964 in FTO), and a genetic score combining these three variants, showed significant interactions with birth-weight in relation to BMI. Among women with birth-weight <3200 g, there was an inverse association between genetic score and BMI; beta-coefficient = −0.045 (95% CI −0.104, 0.013) for BMI at age 18, and −0.055 (95% CI −0.112, 0.002) for adult BMI. Among women with birth-weight ≥3,200 g, genetic score was positively associated with BMI: beta-coefficient = 0.110 (95% CI 0.051, 0.169) for BMI at age 18 (P for interaction = 0.0002), and 0.112 (95% CI 0.054, 0.170) for adult BMI (P for interaction < 0.0001). Because TMEM18, PCSK1, and FTO are highly expressed in the central nervous system (CNS), our results suggest that low birth-weight may disrupt mechanisms of CNS body weight regulation.