June 25, 2009
Brain Gene Implicated In Obesity

People who carry gene variant NRXN3 have a 10-15% increased risk of obesity.

June 26, 2009 - (BRONX, NY) - A variation in a gene that is active in the central nervous system is associated with increased risk for obesity, according to an international study in which Albert Einstein College of Medicine of Yeshiva University played a major role. The research adds to evidence that genes influence appetite and that the brain plays a key role in obesity.

Robert Kaplan, Ph.D., associate professor of epidemiology & population health, helped direct the international study, which involved 34 research institutions and is published online in PLoS Genetics. Dr. Kaplan and his U.S. and European colleagues found that people who have inherited the gene variant NRXN3 have a 10-15 percent increased risk of being obese compared with people who do not have the variant.

The researchers examined data from eight studies involving genes and body weight. These studies included more than 31,000 people of European origin, ages 45 to 76, representing a broad range of dietary habits and health behaviors.

After analyzing more than two million regions of the human genome, the researchers found that the NRXN3 gene variant ─ previously associated with alcohol dependence, cocaine addiction, and illegal substance abuse ─ also predicts the tendency to become obese. Altogether, researchers found the gene variant in 20 percent of the people studied.

NRXN3 has also been implicated in addiction.

Since NRXN3 is active in the brain and also implicated in addiction, these traits may share some neurologic underpinnings.

Here's the paper:

Central abdominal fat is a strong risk factor for diabetes and cardiovascular disease. To identify common variants influencing central abdominal fat, we conducted a two-stage genome-wide association analysis for waist circumference (WC). In total, three loci reached genome-wide significance. In stage 1, 31,373 individuals of Caucasian descent from eight cohort studies confirmed the role of FTO and MC4R and identified one novel locus associated with WC in the neurexin 3 gene [NRXN3 (rs10146997, p = 6.4×10−7)]. The association with NRXN3 was confirmed in stage 2 by combining stage 1 results with those from 38,641 participants in the GIANT consortium (p = 0.009 in GIANT only, p = 5.3×10−8 for combined analysis, n = 70,014). Mean WC increase per copy of the G allele was 0.0498 z-score units (0.65 cm). This SNP was also associated with body mass index (BMI) [p = 7.4×10−6, 0.024 z-score units (0.10 kg/m2) per copy of the G allele] and the risk of obesity (odds ratio 1.13, 95% CI 1.07–1.19; p = 3.2×10−5 per copy of the G allele). The NRXN3 gene has been previously implicated in addiction and reward behavior, lending further evidence that common forms of obesity may be a central nervous system-mediated disorder. Our findings establish that common variants in NRXN3 are associated with WC, BMI, and obesity.

Another paper from the same issue of Plos Genetics finds still more genes that influence obesity and fat distribution.

Here, we describe a meta-analysis of genome-wide association data from 38,580 individuals, followed by large-scale replication (in up to 70,689 individuals) designed to uncover variants influencing anthropometric measures of central obesity and fat distribution, namely waist circumference (WC) and waist–hip ratio (WHR). This work complements parallel efforts that have been successful in defining variants impacting overall adiposity and focuses on the visceral fat accumulation which has particularly strong relationships to metabolic and cardiovascular disease. Our analyses have identified two loci (TFAP2B and MSRA) associated with WC, and a further locus, near LYPLAL1, which shows gender-specific relationships with WHR (all to levels of genome-wide significance). These loci vary in the strength of their associations with overall adiposity, and LYPLAL1 in particular appears to have a specific effect on patterns of fat distribution. All in all, these three loci provide novel insights into human physiology and the development of obesity.

Expect to see a continued acceleration of the rate of gene searches looking for genetic variants that cause behavioral and health differences. Genetic sequencing and genetic testing costs have fallen so fast that the full effect of the price drops hasn't filtered through to published papers. The price drops continue because the technology continues to advance rapidly. So the amount of data available for gene searches keeps going up faster. This flood of data is going to lead to a flood of findings. The most dramatic consequence will be a big acceleration in human evolution.

Share |      Randall Parker, 2009 June 25 11:14 PM  Brain Appetite


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