Widespread but moderate genetic overlap between circulating polyunsaturated fatty acids and brain disorders

Area of Science:

• Neuroscience
• Genetics
• Nutritional Science

Background:

• Polyunsaturated fatty acids (PUFAs) are crucial for brain health.
• PUFA imbalances are linked to major depressive disorder (MDD) and anxiety.
• The genetic links between PUFAs and brain disorders are not fully understood.

Purpose of the Study:

• To investigate the shared genetic basis between circulating PUFAs and 20 brain disorders.
• To identify specific genetic variants and potential causal relationships.
• To explore the genetic determinants of PUFA-brain disorder associations.

Main Methods:

• Genome-wide association studies (GWAS) on PUFAs (N=114,999) and brain disorders (N=9,725-762,917).
• Analysis of genetic correlation, polygenic overlap, and two-sample Mendelian randomization (MR).
• Colocalization and statistical fine-mapping to pinpoint shared variants and causal genes.

Main Results:

• Identified a moderate shared genetic basis for 77 PUFA-brain disorder pairs.
• MR suggested potential causal links for 16 pairs.
• Discovered 40 shared loci, including key genes in lipid metabolism (e.g., GCKR, FADS2, ADARB1).

Conclusions:

• A significant shared genetic architecture exists between PUFAs and brain disorders.
• Specific shared variants and potential causal effects were identified.
• PUFAs may influence MDD and alcohol consumption, warranting further investigation.