Parental diabetes and birthweight in 236 030 individuals in the UK biobank study.
BACKGROUND
The UK Biobank study provides a unique opportunity to study the causes and consequences of disease. We aimed to use the UK Biobank data to study the well-established, but poorly understood, association between low birthweight and type 2 diabetes.


METHODS
We used logistic regression to calculate the odds ratio for participants' risk of type 2 diabetes given a one standard deviation increase in birthweight. To test for an association between parental diabetes and birthweight, we performed linear regression of self-reported parental diabetes status against birthweight. We performed path and mediation analyses to test the hypothesis that birthweight partly mediates the association between parental diabetes and participant type 2 diabetes status.


RESULTS
Of the UK Biobank participants, 277 261 reported their birthweight. Of 257 715 individuals of White ethnicity and singleton pregnancies, 6576 had type 2 diabetes, 19 478 reported maternal diabetes (but not paternal), 20 057 reported paternal diabetes (but not maternal) and 2754 participants reported both parents as having diabetes. Lower birthweight was associated with type 2 diabetes in the UK Biobank participants. A one kilogram increase in birthweight was associated with a lower risk of type 2 diabetes (odds ratio: 0.74; 95% CI: 0.71, 0.76; P = 2 × 10(-57)). Paternal diabetes was associated with lower birthweight (45 g lower; 95% CI: 36, 54; P = 2 × 10(-23)) relative to individuals with no parental diabetes. Maternal diabetes was associated with higher birthweight (59 g increase; 95% CI: 50, 68; P = 3 × 10(-37)). Participants' lower birthweight was a mediator of the association between reported paternal diabetes and participants' type 2 diabetes status, explaining 1.1% of the association, and participants' higher birthweight was a mediator of the association between reported maternal diabetes and participants' type 2 diabetes status, explaining 1.2% of the association.


CONCLUSIONS
Data from the UK Biobank provides the strongest evidence by far that paternal diabetes is associated with lower birthweight, whereas maternal diabetes is associated with increased birthweight. Our findings with paternal diabetes are consistent with a role for the same genetic factors influencing foetal growth and type 2 diabetes.
['Tyrrell|Jessica S|JS|', 'Yaghootkar|Hanieh|H|', 'Freathy|Rachel M|RM|', 'Hattersley|Andrew T|AT|', 'Frayling|Timothy M|TM|']
D000328:Adult D000368:Aged D018070:Biological Specimen Banks D001724:Birth Weight D015331:Cohort Studies D003924:Diabetes Mellitus, Type 2 D005260:Female D006801:Humans D007230:Infant, Low Birth Weight D016014:Linear Models D016015:Logistic Models D008297:Male D008875:Middle Aged D016017:Odds Ratio D010290:Parents D012307:Risk Factors D006113:United Kingdom
birthweight UK Biobank Type 2 diabetes genetics parental history