A novel study of twins who have significant intrapair differences in body mass index (BMI) shows that in the majority of cases, the twin with the higher BMI is the one that veers from their genetic predisposition, based on a polygenic risk score (PRS) for BMI.
While previous studies have evaluated curious cases of differences in weight between twins, the study is unique in investigating whether the higher or lower weighted twin deviates from their genetic predisposition.
The study included 3227 twin pairs of the same gender from the Older Finnish Twin Cohort, consisting of twins born before 1958 and alive in 1974 in Finland.
Of the twins, 34% were monozygotic twins. They were examined at approximately age 30 in 1975 and then followed up in 1981, 1990, and 2011.
Using a PRS developed from nearly 1 million single nucleotide polymorphisms (SNPs) identified in genome-wide association studies, the participants’ BMIs in 1975 were determined to be either within (± 2.0), below (< 2.0), or above (> + 2.0) their genetically predicted BMI.
Personal characteristics and BMI were self-reported through questionnaires and weight and height measurements.
Among the twin pairs, the twin with the higher BMI of the two more frequently deviated from their genetically predicted BMI (approximately two thirds) compared with the lower-weight twin, while those who were the lower weight of the two deviated from their predicted BMI approximately a third of the time.
Overall, between 1975 and 2011, as individuals aged from their 30s to their 60s, all generally bumped up to the next BMI level: Those who were below BMI predictions in 1975 were normal by 2011; those who were normal in 1975 were overweight in 2011; and those who were overweight had become obese over the 36-year study period.
Their mean BMI increase across the time periods, overall, was 4.5 kg/m2.
The findings offer clues to susceptibility or resistance to weight gain, “providing valuable new insights into the etiology and pathophysiology of obesity,” the authors report.
“Via categorizing an individual’s BMI as below, within, or above the genetic predisposition to BMI, we can separately investigate individuals who have been either susceptible or resistant to weight gain, which could provide valuable new insights into the etiology and pathophysiology of obesity,” the authors explain in the study.
“This novel approach opens doors to uncover the protective and detrimental factors that precede weight gain, offering valuable insights into how people can maintain a healthy weight,” said first author Bram J. Berntzen, PhD, of the Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland, in a press statement.
The study was published in Obesity in November 2023.
Limitations include that the PRS is not perfect as an independent predictor as it always depends on genes as well as the environment, and therefore cannot comprehensively explain BMI.
Furthermore, BMI is also imperfect as a determinant of obesity.
The authors report no relevant financial relationships.
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