Shared genetic basis informs the roles of polyunsaturated fatty acids in brain disorders.
Shared genetic basis informs the roles of polyunsaturated fatty acids in brain disorders.
复制标题
共同的遗传基础揭示了多不饱和脂肪酸在大脑疾病中的作用。
DOI：
10.1101/2023.10.03.23296500
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Ye,Kaixiong
中科院分区：
文献类型：
--
作者：
Xu,Huifang;Sun,Yitang;Francis,Michael;Cheng,ClaireF;Modulla,NityaTR;Brenna,JThomas;Chiang,CharlestonWK;Ye,Kaixiong
神经组织富含多不饱和脂肪酸（PUFA），这是神经元正常功能（如神经传递）不可或缺的成分。PUFA营养缺乏和不平衡与各种慢性脑部疾病有关，包括重度抑郁症（MDD），焦虑和厌食症。然而，PUFAs对大脑疾病的影响仍然没有定论，其共同遗传决定因素的程度在很大程度上是未知的。在这里，我们使用全基因组关联汇总统计系统地检查了六种循环PUFA表型（N = 114，999）和20种脑部疾病（N = 9，725 - 762，917）之间的共享遗传基础，推断它们的潜在因果关系，识别共定位区域，并查明共享遗传变异。遗传相关性和多基因重叠分析揭示了广泛共享的遗传基础之间的77个性状对6个PUFA表型和16个脑疾病。双样本孟德尔随机化分析表明，16对PUFA与脑部疾病（包括饮酒、双相情感障碍（BIP）和MDD）存在潜在因果关系。共定位分析在6种PUFA和10种脑部疾病中发现了40个共享基因座（13个独特）。22个独特的变异被统计学推断为候选共享因果变异，包括rs 1260326（GCKR），rs 174564（FADS 2）和rs 4818766（ADARB 1）。这些发现揭示了PUFAs和大脑疾病之间广泛共享的遗传基础，确定了特定的共享变体，并为PUFAs对某些大脑疾病的潜在影响提供了支持，特别是MDD，BIP和饮酒。
The neural tissue is rich in polyunsaturated fatty acids (PUFAs), components that are indispensable for the proper functioning of neurons, such as neurotransmission. PUFA nutritional deficiency and imbalance have been linked to a variety of chronic brain disorders, including major depressive disorder (MDD), anxiety, and anorexia. However, the effects of PUFAs on brain disorders remain inconclusive, and the extent of their shared genetic determinants is largely unknown. Here, we used genome-wide association summary statistics to systematically examine the shared genetic basis between six phenotypes of circulating PUFAs (N = 114,999) and 20 brain disorders (N = 9,725–762,917), infer their potential causal relationships, identify colocalized regions, and pinpoint shared genetic variants. Genetic correlation and polygenic overlap analyses revealed a widespread shared genetic basis for 77 trait pairs between six PUFA phenotypes and 16 brain disorders. Two-sample Mendelian randomization analysis indicated potential causal relationships for 16 pairs of PUFAs and brain disorders, including alcohol consumption, bipolar disorder (BIP), and MDD. Colocalization analysis identified 40 shared loci (13 unique) among six PUFAs and ten brain disorders. Twenty-two unique variants were statistically inferred as candidate shared causal variants, including rs1260326 (GCKR), rs174564 (FADS2) and rs4818766 (ADARB1). These findings reveal a widespread shared genetic basis between PUFAs and brain disorders, pinpoint specific shared variants, and provide support for the potential effects of PUFAs on certain brain disorders, especially MDD, BIP, and alcohol consumption.