Family-based association study of 76 candidate genes in bipolar disorder: BDNF is a potential risk locus

The findings will need to be confirmed by additional studies.

Bipolar disorder is an episodic illness characterized by extreme disturbances in mood, including mania and depression. Family and twin studies have demonstrated a strong genetic basis for this disease but classical linkage studies‹studies of inheritance patterns within families‹have not found conclusive evidence for any one gene. Several studies have implicated various genes as culprits, although a definitive genetic cause does not exist.

Scientists have long considered the possibility that bipolar disorder is a complex disease, caused by several genes, each of which exerts a modest increase in relative risk in the population. Such types of risks are difficult to discover by linkage analysis, which typically focuses on extended families. Complex genetic diseases may best be dissected by so-called "association" studies, which analyze DNA from multiple large groups of patients in the general population and detects the effect of a SNP--a single letter variation in a gene-- on a disease risk.

In this study, scientists undertook a systematic approach, identifying from the literature 76 candidate genes previously implicated in bipolar disorder and then identifying the SNPs in these genes.

Using highthroughput genotyping technology at the Whitehead Genome Center, they then analyzed the patterns of inheritance of these SNPs from parents to their children with bipolar disorder. They found that a single SNP that causes an amino acid change in the BDNF protein is associated with bipolar disorder. This SNP is part of a larger haplotype‹a set of SNPs that travel together--that resides on BDNF and seems to be the only one associated with an increased risk for bipolar illness. This pattern of risk was not found for any of the other 75 candidate genes they studied.

"Our study of 76 genes has narrowed down the search to BDNF‹but further studies will need to confirm our results," says Pamela Sklar, first author and researcher at the Whitehead and Psychiatric and Neurodevelopmental Genetics Unit at MGH.

BDNF is a gene found on chromosome 11 and belongs to a family of so-called neurotrophins--nerve chemicals that promote the growth and survival of neurons.

For more information, contact:
Seema Kumar, 617.252.1420